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Norbert & Suzanne Schnog Lecture/"The Evolving Landscape of Colorectal Cancer in 2022"

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Norbert & Suzanne Schnog Lecture/"The Evolving Landscape of Colorectal Cancer in 2022"

March 02, 2022

Yale Cancer Center Grand Rounds | March 1, 2022

Presentation by: Dr. Cathy Eng

ID
7493

Transcript

  • 00:0032 Cancer Center grain grand rounds.
  • 00:03I'm making a guest appearance today
  • 00:04and I can't say that it's wonderful
  • 00:06to be a guest in introducing a very
  • 00:09special speaker who is Doctor Kathy
  • 00:11Yang and many of us know Doctor Ang
  • 00:14who is very well known in the field of
  • 00:18Colt GI Malignancies and Doctor Lang.
  • 00:20Is the David Johnson chair and surgical
  • 00:23and medical oncology, and she's Co.
  • 00:25Leader of the GI Cancers research program.
  • 00:28At Vanderbilt, she's also, I think Co.
  • 00:30Director of the OR Director of the Young
  • 00:33Adults Cancer Initiative and started at
  • 00:35Vanderbilt about a couple years ago,
  • 00:37so really has done phenomenally.
  • 00:41Kathy received her MD from Hahnemann
  • 00:43and then her residency in internal
  • 00:45medicine at Russia and then did her
  • 00:47fellowship in hematology oncology at
  • 00:49the University of Chicago and then
  • 00:51spent majority of her life at MD.
  • 00:54Anderson focused on what is close to,
  • 00:57I think several of our hearts in
  • 00:58in focused on colorectal cancers,
  • 01:00GI cancers and translational research and
  • 01:03what impact can we do in in those fields.
  • 01:07She also played important roles in
  • 01:09faculty governance. I was excited to see.
  • 01:11Kathy ticker roll in as in the
  • 01:14faculty Senate,
  • 01:15which often is an important piece
  • 01:16and then move to Vanderbilt in 2019.
  • 01:19Her interest has been in clinical
  • 01:21trials and how can we define novel
  • 01:24drugs for treatment of these cancers.
  • 01:26And as I mentioned,
  • 01:28is also beyond focus on the young adult
  • 01:30colorectal cancer patients has also
  • 01:32focused on role of immunotherapy in HP.
  • 01:35Associated Cancers has published many,
  • 01:37many papers on these fields
  • 01:39and has led many trials.
  • 01:41I'm not going to enumerate.
  • 01:42All of the her leadership roles in
  • 01:45the various national societies in
  • 01:47ASCO ASCO GI E Cog and see I most
  • 01:51recently that rang was chosen as the
  • 01:53Vice chair of the swag GI Committee
  • 01:56and NCI GI Steering Committee and also
  • 01:58has focused on workforce shortages.
  • 02:00So overall,
  • 02:01what I would describe as not only
  • 02:03a talented clinician,
  • 02:04but also thinking about our field
  • 02:06and oncology and the broader things
  • 02:08that guide us.
  • 02:09So really looking forward to her
  • 02:12presentation today. Welcome, Kathy.
  • 02:13You're only sorry this is virtual.
  • 02:16Well, thank you so much and let me go
  • 02:20ahead and share my screen. And. Sorry.
  • 02:35OK, did did it come across OK?
  • 02:38Perfect so today is March 1st,
  • 02:41so it's colorectal Cancer Awareness Month,
  • 02:43so I am delighted to participate in
  • 02:47this session with all of you today.
  • 02:49With so many familiar faces and
  • 02:52thank you so much for inviting me.
  • 02:55So we'll just be touching up on kind of the
  • 02:59general field regarding colorectal cancer,
  • 03:01since it seems appropriate for March
  • 03:04colorectal Cancer Awareness Month.
  • 03:06And these are the topics we'll be discussing.
  • 03:12And these are my disclosures.
  • 03:15So friendly reminder for those
  • 03:17that are don't treat colorectal
  • 03:19cancer in a regular basis.
  • 03:21It is expected in 2022 that 151,000
  • 03:24individuals will be diagnosed with
  • 03:26this disease and about 45 thousand
  • 03:28of those will be rectal carcinoma.
  • 03:30It still remains the second leading
  • 03:31cause of cancer death for men and
  • 03:33women combined and the meeting age.
  • 03:34As many of you are aware is
  • 03:36usually in the late 60s,
  • 03:37but I'm going to be touching upon
  • 03:39that because of my own interest in
  • 03:41early onset colorectal cancer and
  • 03:43for as long as I've been in practice.
  • 03:46Unfortunately,
  • 03:46the five year survival for our stage
  • 03:49four patient population has basically
  • 03:51only changed from about 13 to 14%,
  • 03:53and it looks closer now to 15%.
  • 03:56Based upon these numbers.
  • 04:01Friendly reminder as well for
  • 04:02the majority of our patients.
  • 04:04Unfortunately they do not have an
  • 04:07inherited form of colorectal cancer
  • 04:09such as Lynch syndrome or FAP.
  • 04:11In the majority of cases are
  • 04:13going to be sporadic and that's
  • 04:16why this is very difficult.
  • 04:19Cancer for us to tackle because I
  • 04:22believe it's largely multifactorial.
  • 04:24I'm not going to be touching
  • 04:26upon the very basic information
  • 04:27regarding chemotherapy because
  • 04:29most of the literature nowadays
  • 04:31is about molecular subsets,
  • 04:33and I'll touch upon the more recent
  • 04:35data on some of those subsets.
  • 04:37But for us for any stage
  • 04:404 surgically unresectable,
  • 04:41patient or patient that is going
  • 04:43to receive neoadjuvant therapy
  • 04:45with metastatic disease prior
  • 04:47to surgical resection,
  • 04:48we often consider the use of systemic
  • 04:50chemotherapy and the most common regimens,
  • 04:52as many of you are familiar with.
  • 04:54May include folfox or folfiri
  • 04:55with the consideration of a
  • 04:57targeted agents such as berbasis,
  • 04:59ma'am or anti EGFR therapy
  • 05:01such as PM AB or C tax map.
  • 05:05If the patient is rest wild type.
  • 05:07If the patients treatment naive if
  • 05:09they don't have a right sided tumor,
  • 05:11we may want to consider anti EGFR therapy,
  • 05:13although that is not my personal preference.
  • 05:15I tend to reserve it for further
  • 05:18down the line and then full Fox
  • 05:20Erie for a patient that is well
  • 05:23with good performance status.
  • 05:24Fair reasonable file with the high
  • 05:26response rate of 65 to 78% and then
  • 05:28of course we have our oral agents
  • 05:30regorafenib and lonsurf that are
  • 05:32currently FDA approved as single
  • 05:35agents in the refractory setting
  • 05:36and then last but not least,
  • 05:38the rare subtypes currently.
  • 05:40Our median survival for all stage four
  • 05:43patients is roughly 32 to 34 months
  • 05:45for the general patient population,
  • 05:47but once again,
  • 05:48right sided tumors do not appear
  • 05:50to fear as well in regards
  • 05:52to overall survival for our.
  • 05:54Either Rasputin patients and
  • 05:56then our right side of patients.
  • 05:59And these are the molecular subsets that
  • 06:02we've largely been focused on recently.
  • 06:05Queiroz is the most common mutations.
  • 06:07Majority of our patients,
  • 06:08but we do like to take into account other
  • 06:11rare RASK mutations such as N Rasen d'etre,
  • 06:14and then we do have some
  • 06:16other rare mutations,
  • 06:16including MSI high,
  • 06:18which will be discussing the BRAF mutation,
  • 06:20which is less than 10% of our
  • 06:23patient population with V600E.
  • 06:24PIK 3 CA is being investigated,
  • 06:27as in clinical trials and then.
  • 06:30And then there's the end track fusion,
  • 06:31which I will not be touching upon,
  • 06:33because that's extremely rare
  • 06:34and have yet to see a patient
  • 06:36with the interact fusion.
  • 06:38But I'm always curious when people tell
  • 06:40me they've had one occasional patient,
  • 06:42and that's less than 1% of all patients.
  • 06:46So for all of our patients
  • 06:48with metastatic disease,
  • 06:49I'm going to be focusing on that in large
  • 06:51part for this talk and then touching
  • 06:53upon a little bit on early stage,
  • 06:55colon and rectal if brief time.
  • 06:57But next generation sequencing is extremely
  • 06:59important for our patient population,
  • 07:01and identifying once again those
  • 07:03mutations that I mentioned.
  • 07:05And these are some of the
  • 07:07aspects will be touching upon.
  • 07:08Once again, MSI Grass B RAF
  • 07:11and her two amplification.
  • 07:16For MSI high colorectal carcinoma patients,
  • 07:19which represent less than 10%
  • 07:20of our patient population.
  • 07:23This is one of the most important
  • 07:25studies to date for MSI high patients,
  • 07:27and I'm sure many of you are familiar with
  • 07:30the role of pembrolizumab in treatment.
  • 07:33Naive MSI high colorectal carcinoma patients.
  • 07:36This was basically a one to one
  • 07:38randomization that has since been
  • 07:40updated in regards to overall survival
  • 07:43compared to standard chemotherapy,
  • 07:45and in this case was two primary endpoints,
  • 07:47PFS and OS, and the results were extremely
  • 07:51impressive when they were originally.
  • 07:54Presented and eventually published.
  • 07:55And this is looking at the progression free
  • 07:58survival for our MSI high treatment naive
  • 08:01patients when receiving Pember Lizum app.
  • 08:03This is single agent pembrolizumab.
  • 08:05Now you may say that there's a crossover
  • 08:08in about 1/3 of patients in those that
  • 08:10did receive Pember Lizum app at 1st and
  • 08:12did not appear to benefit from this drug.
  • 08:14And unfortunately we don't have the exact
  • 08:16etiology to account for this right now.
  • 08:18But as you can see here,
  • 08:19the PFS was twice as high for
  • 08:22that versus standard chemotherapy
  • 08:24for the majority of patients.
  • 08:27And the OS has also been determined
  • 08:30to be of significance in the sense
  • 08:33that there was crossover loud.
  • 08:35Once again, this is a Co primary endpoint,
  • 08:37so 60% of patients were allowed to
  • 08:40crossover to receive IO therapy,
  • 08:42and so that that is obviously an issue when
  • 08:44I'm looking at your statistical significance.
  • 08:47The prespecified P value
  • 08:49was supposed to be 0.0246,
  • 08:51so they did not meet its pre
  • 08:54specified value for OS,
  • 08:56however.
  • 08:56Obviously I would say we can clearly see
  • 09:00that there was crossover 60% of patients,
  • 09:02and that's likely accounted for
  • 09:04this and also keeping in mind this
  • 09:06is really considered the standard
  • 09:08of care for these patients.
  • 09:09Now what is the other 1/3 of patients that
  • 09:12do not appear to benefit from IO therapy?
  • 09:15Once again,
  • 09:16we still have yet to understand why that is,
  • 09:19and obviously it does bring to mind
  • 09:21that is there a potential benefit for
  • 09:24the consideration of chemotherapy,
  • 09:25plus IO therapy?
  • 09:27And that is an ongoing trial by the way.
  • 09:31Looking at response rate,
  • 09:32you can see here 44% versus 33% for
  • 09:36pembrolizumab versus standard chemotherapy.
  • 09:39But what is of great interest?
  • 09:41I think for many of us is the fact
  • 09:43that there may be some potential
  • 09:45benefit for combination therapy.
  • 09:47Now this is a single ARM study,
  • 09:48Checkmate 142 looking at Nebo plus iffy.
  • 09:53It was part of a large study
  • 09:56that we're not comparative arms,
  • 09:59but looking at various cohorts,
  • 10:00and this was in the treatment
  • 10:02naive setting here,
  • 10:03primary endpoint was response and this was
  • 10:06published by Heinz Josef Lenz last fall,
  • 10:10and I told you the response rate was
  • 10:1244% for single agent pembrolizumab.
  • 10:14Keeping in mind this is once
  • 10:15again a small study, 45 patients.
  • 10:17This is not a phase three,
  • 10:19but the response rate was 69% and
  • 10:22as you can see across the board.
  • 10:24Quite impressive response rates and they
  • 10:27reported that the 24 month of OS was 79%,
  • 10:31so it's actually quite impressive
  • 10:33and obviously I think many of us
  • 10:35look forward to learning more about
  • 10:36the benefit of combination therapy
  • 10:38and see if it is truly superior.
  • 10:40But once again, Pember Lizum app has
  • 10:43demonstrated this in a phase three trial.
  • 10:46What are the ongoing trials?
  • 10:48So there is a stage three trials called
  • 10:52Atomic, which is folfox plus or minus 8 SO.
  • 10:55And then, as I mentioned before,
  • 10:56there is a combo study that
  • 10:57was very slow to enrollment.
  • 10:59Hopefully will it will finish
  • 11:00enrollment at some point called commit.
  • 11:02Looking at Folfox plus Bev.
  • 11:04And then it has,
  • 11:05oh there is a Merc platform study
  • 11:07that is also new and ongoing as well.
  • 11:10And in rectal cancer there's actually
  • 11:12some very intriguing data regarding
  • 11:13MSI high and that was just reported.
  • 11:15So we'll touch upon that.
  • 11:18So obviously the results from Pember
  • 11:20Lism AB are quite impressive and
  • 11:23and there was another pilot trial
  • 11:25called the Niche trial looking at a
  • 11:27very very small number of MSI high
  • 11:29patients and looking at the role
  • 11:31MSI and MSI stable patients looking
  • 11:33at the role new Advent IO therapy
  • 11:35in that setting and they noticed
  • 11:37there was some significant benefit.
  • 11:39So why not consider that in an MSI
  • 11:42high rectal patient population
  • 11:43and this trial was actually just
  • 11:46presented by Doctor Loomis who is a.
  • 11:48Fellow at Memorial Sloan Kettering under
  • 11:51the guidance of my friend Andrea Sirsak.
  • 11:54They're looking at the star lamat,
  • 11:56so here locally advanced MSI high
  • 11:58rectal cancer stage two stage three.
  • 12:01They gave six months of Dystar lemon
  • 12:03and then they wanted to look at
  • 12:06basically their response by endoscopy
  • 12:08as well as by imaging and the
  • 12:11primary end point here is response.
  • 12:12Now be results from this trial were
  • 12:15so impressive that they decided to go
  • 12:17ahead and provide the presentation on
  • 12:19the 1st 11 out of 16 patients enrolled.
  • 12:22The total number of patients expect.
  • 12:25Roll and roll in. This trial is 30 patients.
  • 12:28And here is what they call clinical
  • 12:30complete response.
  • 12:30Once again is the endoscopic CR
  • 12:33plus the radiographic CR and they
  • 12:36required all patients to have an MRI.
  • 12:38And this was the patient population.
  • 12:40Just to give you an idea real quick,
  • 12:41I'm just going to touch up on the key points.
  • 12:43A lot of patients were T3T4 a lot
  • 12:46of patients were node positive.
  • 12:47These were MSI high,
  • 12:50but all were BRAF wild type.
  • 12:53And this is the very early results.
  • 12:55We do not have long term results,
  • 12:57just early results of the 1st 11
  • 12:59patients out of the 16 enrolled this
  • 13:01far and they reported a complete CR.
  • 13:04And in this study in fact they omitted
  • 13:06the consideration of radiation and surgery.
  • 13:08So do keep that in mind in this
  • 13:11patient population.
  • 13:12Obviously single institution study
  • 13:14we need more follow up and I'd
  • 13:16like to see this data validated
  • 13:18now in Full disclosure.
  • 13:19Kristen See Amber who I'm helping to mentor
  • 13:21and I worked with her extensively on this.
  • 13:23Protocol we had actually created this
  • 13:27national trial supported by Ekaki,
  • 13:29a 2201 looking at New Advent Niveau
  • 13:32EP also in the MSI high patient
  • 13:34population with the consideration of
  • 13:36five by five radiation therapy and then
  • 13:40also the consideration of sphincter
  • 13:42preservation here primary endpoint was
  • 13:44Patsy R because the findings from Asco
  • 13:47GI from Doctor Loomis this trial is
  • 13:49going to undergo some rapid amendment
  • 13:52to maybe allow the consideration.
  • 13:55Of not necessarily requiring 5 by 5
  • 13:58radiation therapy unless there's bulky
  • 14:01tumor and adenopathy and obviously
  • 14:03once again it's very interesting
  • 14:04'cause we actually recommended the
  • 14:06consideration of making sphincter
  • 14:08preservation as a primary endpoint.
  • 14:10But when we originally wrote this trial,
  • 14:12we were told that that was being too
  • 14:14progressive and here we are today
  • 14:16trying to amend this trial to keep up.
  • 14:17But once again,
  • 14:18this is a national trial and we
  • 14:20will remain open and we hope to
  • 14:22enroll these patients once again.
  • 14:24Pilot study of roughly.
  • 14:2631 patients as well.
  • 14:29What about our Brafman patients?
  • 14:31Well,
  • 14:31for our MSI stable be wrapping in patients,
  • 14:34it's very poor prognostic
  • 14:36factor for these patients.
  • 14:38It's less than 9% of our patient population.
  • 14:40Unlike Melanoma,
  • 14:41single agent Byref inhibitors
  • 14:43have not been impressive with
  • 14:45response rate of less than 5%,
  • 14:46and we noted that there were basically
  • 14:49escape mechanisms in colorectal cancer in
  • 14:52comparison to the success that was seen
  • 14:54in Melanoma with standard chemotherapy,
  • 14:56the median overall survival
  • 14:58is only 12 to 14 months.
  • 15:00And So what can we do?
  • 15:01How can we basically not only
  • 15:03utilize our B RAF inhibitors?
  • 15:06But how can we also consideration
  • 15:08other downstream impact?
  • 15:09And so here we have the combination.
  • 15:12Basically with Ralph,
  • 15:13Egypt are and then there was an
  • 15:15attempt in combination with Mac.
  • 15:17This was the B control,
  • 15:19so the B control had a triplet versus the
  • 15:22doublet versus standard chemotherapy.
  • 15:24For patients that have received at
  • 15:26least one prior line of therapy
  • 15:28for B RAF meeting V.
  • 15:30600.
  • 15:30Mutation and the doublet was determined
  • 15:32to be just as successful as the triplet,
  • 15:35and this was FDA approved.
  • 15:37This is the regimen called B raft OD,
  • 15:40and it resulted in OS of nine point 3
  • 15:42months versus standard chemotherapy.
  • 15:44Now what's really interesting is
  • 15:46they decided to examine that regimen
  • 15:48because it seemed to be the most
  • 15:49successful and try to move it up
  • 15:51front to the treatment naive setting.
  • 15:52And this is the anchor trial which was
  • 15:55reported at ESMO and I show it here.
  • 15:56'cause this has since been updated as well.
  • 15:59At ESMO last year.
  • 16:00And they reported a response rate
  • 16:03of about 50%.
  • 16:04However, the PFS was only about four months,
  • 16:07and so that was clearly not a home
  • 16:10run for a treatment naive patient.
  • 16:13So at this year's Oscar GI just
  • 16:15a couple weeks ago, Dan Morris,
  • 16:17so I'm so very proud of.
  • 16:18From MD Anderson has completed this
  • 16:21pilot trial at MD Anderson looking at
  • 16:23end crafted and so text amount so the
  • 16:26beer F to V but in combination with
  • 16:28immune checkpoint inhibition with
  • 16:30nivolumab in this setting and this is
  • 16:32in previously treated patients and the
  • 16:34reason for that is because there appears
  • 16:36to be a higher immune activation and
  • 16:38higher team be in this patient population.
  • 16:41And as you know some of the
  • 16:42B RAF subtypes actually.
  • 16:44Are very similar to this one.
  • 16:46So more likely to respond to IO therapy,
  • 16:49single institution study, small numbers,
  • 16:51important to keep in mind.
  • 16:54And here's the primary endpoint response,
  • 16:56and these were the doses that
  • 16:57were provided to these patients.
  • 16:58Keeping in mind these patients need a
  • 17:01better option as they just showed you,
  • 17:03they don't do well with standard
  • 17:05chemotherapy therapy,
  • 17:05and even with RAF target therapy,
  • 17:09they still need a better response.
  • 17:12So once again,
  • 17:14single institution very thought provoking.
  • 17:17They report a response rate 50%
  • 17:19so not much higher than what was
  • 17:21already reported in the prior study.
  • 17:23However,
  • 17:23the PFS was a little bit higher at 7.4
  • 17:26months, and the OS was 15.1 months.
  • 17:29This is after a medium fault time
  • 17:31of 16 months.
  • 17:32Now these results were impressive
  • 17:34enough that now this is going to
  • 17:37be a national trial swab 2107 with
  • 17:39a 2 to one randomization of the
  • 17:42addition of BIOTHERAPY.
  • 17:43At a study less than 75 patients,
  • 17:46this should be opening up.
  • 17:47This is March,
  • 17:48so it should be opening up at
  • 17:50the latter part of April and we
  • 17:52are excited about this trial.
  • 17:53It allows one to two prior lines of therapy,
  • 17:56so that's in your previously
  • 17:58treated brip patients.
  • 17:59If you have any patient
  • 18:01starting in the next two months,
  • 18:02please consider this trial when
  • 18:04it is open at time to activate
  • 18:06it at your institution.
  • 18:07Now there is a phase three trial
  • 18:10that is ongoing for these patients
  • 18:12and I also want to highlight this
  • 18:15because it is the only phase three
  • 18:17trial in treatment naive patients.
  • 18:19So this is a one to one to one
  • 18:25randomization of basically beer after V.
  • 18:27So end carafe,
  • 18:28and if the BRAF inhibitor plus the
  • 18:30text map or that same combination
  • 18:33be wrapped heavy plus folfox,
  • 18:35they've actually decided not
  • 18:36to proceed with full fury.
  • 18:37That was part of the run in phase
  • 18:39and so does now with Folfox.
  • 18:41This phase three arm just opened
  • 18:43about two weeks ago and then the
  • 18:46control arm is standard chemotherapy,
  • 18:48so this trial is largely being run
  • 18:50in Europe and they're about 9 sites.
  • 18:52The last time I checked in the United States,
  • 18:54we are one of the sites that
  • 18:55are participating in this trial.
  • 18:56Once again,
  • 18:57we really need to find an option
  • 18:59for these patients with very
  • 19:01poor prognosis otherwise,
  • 19:02so please consider enrollment to this trial.
  • 19:07I wanted to just briefly touch upon her too,
  • 19:09'cause there's a lot of interest and direct.
  • 19:11Can I know that many of you are
  • 19:13familiar with direct can because it is
  • 19:15proved in gastric and breast cancer,
  • 19:17but her two positivity is extremely
  • 19:20rare in colorectal cancer,
  • 19:22unlike a gastric and breast cancer,
  • 19:24it's about 4% of our patients,
  • 19:27and once again it is required to be 3 plus
  • 19:30by IHC or fish amplified and IHC 2 plus.
  • 19:34So ongoing studies that I will
  • 19:35not be touching upon 'cause they.
  • 19:37Finished enrollment,
  • 19:38but have not yet been reported yet.
  • 19:40There's swag 1613,
  • 19:41which is treasure map plus produce
  • 19:43a map versus standard chemotherapy
  • 19:46in the previously treated setting,
  • 19:48and then the Mountaineer study was
  • 19:50to catnip plus restitution amount.
  • 19:53Now I'll just be touching on destiny
  • 19:55because this was a recently updated as well.
  • 19:58So Destiny is looking at an antibody
  • 20:01drug conjugate,
  • 20:02which is direct can and this trial
  • 20:04it was extremely interesting for
  • 20:06many of us in colorectal cancer
  • 20:08because it's number one.
  • 20:09It's a different type of drug and
  • 20:11#2 they allowed patients that have
  • 20:14had prior anti her two therapy.
  • 20:16You'll see here they provided the
  • 20:186.4 milligram per kilogram dose and I
  • 20:20mention that because there's a second
  • 20:22study that is also testing the dose.
  • 20:23Currently that is open and this is
  • 20:26at Q three weeks you'll see cohort.
  • 20:29Today is your IHC 3 plus patient
  • 20:32population or your fish positive
  • 20:34cohort B is I see two plus and the
  • 20:37cohort C is IHC one plus primary
  • 20:40endpoint was response.
  • 20:41'cause keeping in mind these
  • 20:43are small patient population.
  • 20:46And here focusing on Cohort 8,
  • 20:48that's really where your focus should be.
  • 20:5153 patients of those 53 patients,
  • 20:5424 had a response,
  • 20:55and these were heavily pretreated patients.
  • 20:58If I recall correctly,
  • 20:59the median line of therapies was free and
  • 21:02and basically the response rate was 45%.
  • 21:05So once again it can be provided
  • 21:07to a patient.
  • 21:09That's her two positive that
  • 21:11that is naive to trust its map,
  • 21:13or it can be provided to a patient that has.
  • 21:16Had progression of disease which
  • 21:18has treasuries map and this could
  • 21:20be an option now very similar to
  • 21:22the studies in breast and gastric.
  • 21:24There is a known toxicity as
  • 21:26many of you are aware,
  • 21:27with interstitial lung disease,
  • 21:28which is in less than 10%
  • 21:30of the patient population,
  • 21:31but something important to keep in mind.
  • 21:35And then it wanted to touch upon Cara.
  • 21:38So Karas mutation for us in colorectal cancer
  • 21:43has been one of the most common mutations.
  • 21:47Especially when you take into
  • 21:49account your standard crass.
  • 21:50But then you also have your address
  • 21:51and then rest. Which means all
  • 21:53these patients do not benefit.
  • 21:55So that's about 30 to 60% of patients
  • 21:57do not benefit from anti EGFR therapy.
  • 21:59And then recently there's been some
  • 22:02interest looking at drugs that
  • 22:04are specific to the Cross G 12.
  • 22:06The mutation now keeping in
  • 22:07mind this is very, very rare.
  • 22:09In colorectal cancer it's
  • 22:11less than 5% of our patients,
  • 22:13but it is a potential option
  • 22:15now this has been reported,
  • 22:18you probably seen the data already with long,
  • 22:20much more impressive with lung and colon.
  • 22:23Not so impressive as a single agent.
  • 22:27Basically the response rate was
  • 22:28about a little less than 10% and
  • 22:31this was just published recently.
  • 22:33So Teresa is the drug.
  • 22:37Progression free survival was four months.
  • 22:39The medium fall was after this.
  • 22:41After meeting followed 11 months,
  • 22:42the 12 month PFS was only 11% and
  • 22:45now there are obviously looking
  • 22:47at this drug in combination.
  • 22:50So I I look forward to seeing
  • 22:52some of that data.
  • 22:54But I just want to show this,
  • 22:55although not specific to colorectal cancer.
  • 22:58Once again,
  • 22:58this is at aggressive from another
  • 23:01competing company and I wanted to show
  • 23:04this because it was very impressive
  • 23:06in regards to pancreatic cancer.
  • 23:08Once again, the very small numbers,
  • 23:10so I always.
  • 23:11I'm always very hesitant when
  • 23:13I see very early data.
  • 23:15But basically to focus on the
  • 23:18GI patient population and they
  • 23:20reported that there was basically
  • 23:22a response attend in 10 patients.
  • 23:25Five out of those ten had a
  • 23:27response with pancreatic cancer,
  • 23:28which is unheard of as many
  • 23:30can guess because once again,
  • 23:32pancreatic cancer is still remains
  • 23:34a challenge,
  • 23:35and we don't have a lot of novel agents.
  • 23:38This is once again G12C,
  • 23:40which is not the most common RASC
  • 23:42mutation in pancreatic cancer,
  • 23:44but once again could be.
  • 23:45Potentially beneficial,
  • 23:46and then they are looking at it.
  • 23:48Other malignancies very similar
  • 23:49so that to the soeder as they are
  • 23:52looking at it in combination as well.
  • 23:55So just intriguing data from
  • 23:56this year's Oscar GI.
  • 24:00I did want to focus on the role of
  • 24:03circulating tumor DNA, just very briefly,
  • 24:05because there are two ongoing
  • 24:07trials and early stage disease,
  • 24:09and then there was this trial
  • 24:11that was just presented at Asco
  • 24:13GI from the Japanese group.
  • 24:15Doctor Katata called Circulate Japan
  • 24:17and I thought that this was a very very,
  • 24:21very important study that should
  • 24:24receive attention because it
  • 24:26looked at basically all stages.
  • 24:29Colon rectal cancer resectable stage
  • 24:33four they basically obtained pre-op
  • 24:35circulating tumor DNA using the
  • 24:37signature platform and then they
  • 24:39followed the patients at four weeks,
  • 24:4112 weeks, 24 and 36 weeks,
  • 24:43and so they provided their data
  • 24:46regarding the 1st 1000 plus patients
  • 24:47that have been enrolled this far in
  • 24:50this trial and they've compiled it
  • 24:51based upon these three ongoing studies.
  • 24:53As you can see here.
  • 24:56Like Vega Galaxy and Altair.
  • 25:01And what it really shows basically where
  • 25:04we think the field is obviously going.
  • 25:07Here we have some information for
  • 25:09stage one through stage four and and
  • 25:11as you can see here at the disease
  • 25:13free survival if you're circulating
  • 25:15tumor and DNA remain negative with
  • 25:18dramatically different from if you
  • 25:20remained positive and this is at post-op
  • 25:23when compared to baseline at 4 weeks.
  • 25:27And then they continued to look
  • 25:30at their sequential circulating
  • 25:31tumor DNA at 4 weeks and 12 weeks.
  • 25:33And as you can see here,
  • 25:34obviously if it remain negative,
  • 25:36that's a very positive benefit in
  • 25:38regards to disease free survival.
  • 25:40But if you went from negative to
  • 25:42positive that changed your disease
  • 25:43free survival from 98% to 63%.
  • 25:46If you went from positive to negative,
  • 25:49let's say with attachment chemotherapy
  • 25:51that improved your disease free survival
  • 25:53but positive to positive obviously
  • 25:54was not a good prognostic indicator.
  • 25:59And this is looking at the role
  • 26:01of adjuvant chemotherapy here.
  • 26:02If you have a positive circulating tumor DNA,
  • 26:04so very intriguing data,
  • 26:06and probably the largest data to date.
  • 26:09So it's it's just important to note.
  • 26:11And once again the purpose of this
  • 26:13lecture today is kind of give you
  • 26:15an idea of the existing interest
  • 26:16on many of the studies that are
  • 26:18ongoing in colorectal cancer,
  • 26:20so I apologize I missed.
  • 26:26I apologize. There it is.
  • 26:29OK, I was on the right track.
  • 26:30I thought I didn't include this slide so
  • 26:32currently and as many of you that know me,
  • 26:35I'm heavily involved in the NC
  • 26:38cooperative groups with swag and ACOG,
  • 26:40and especially with my role now on
  • 26:42the GI Steering Committee and very
  • 26:44supportive of cooperative group trials.
  • 26:47So this is the COBRA trial looking
  • 26:49specifically at stage 2 colon cancer.
  • 26:51As many of you know,
  • 26:52for stage 2 colon cancer,
  • 26:54as long as I was in fellowship till now,
  • 26:57it's always been a discussion with
  • 26:58the patient about the role of.
  • 26:59Management chemotherapy 'cause it's
  • 27:01never been really well defined and has
  • 27:04not been statistically significant
  • 27:05thus far in any prospective trials.
  • 27:07So here can you utilize the role of
  • 27:10circulating tumor DNA and take some
  • 27:12of this new science so they're using
  • 27:15the Guardian platform and apply it?
  • 27:17And so this is being led by Van Morris,
  • 27:20who I mentioned to you earlier
  • 27:22is running the be raft trial,
  • 27:24looking at patients that are either
  • 27:26just going to receive standard
  • 27:28care with active surveillance.
  • 27:29Or they have their circulating tumor DNA if
  • 27:32there's no circulating tumor DNA detected,
  • 27:35they just go on standard surveillance.
  • 27:38If it is positive,
  • 27:39then they will receive full Fox Orc
  • 27:41pox and so this trial is ongoing.
  • 27:43So if you have stage two,
  • 27:46play patients with colon carcinoma,
  • 27:48please consider enrolling to this trial.
  • 27:52There's also the circulate US study,
  • 27:54which will be led by Chris Lu
  • 27:55and Arvind Dasari.
  • 27:56Once again,
  • 27:56my very close colleagues and I've
  • 27:58had the pleasure of working with them
  • 28:00and mentoring them over the years.
  • 28:02And and now they have their own trial
  • 28:05as well. For stage three patients.
  • 28:08And here if you're circulating
  • 28:09tumor DNA is detected,
  • 28:11you would be randomized to folfox
  • 28:13Erie versus standard capox or folfox.
  • 28:16So this trial should open up any day.
  • 28:18It's had an amendment even before
  • 28:20it was opened,
  • 28:20and that's resulted in a delay in.
  • 28:22About a year.
  • 28:25And other ongoing trial.
  • 28:27So in Full disclosure I am the
  • 28:30one of the national pies here in
  • 28:32the United States. For fresco.
  • 28:332 I just wanted to make sure to keep
  • 28:36this on your radar because this trial
  • 28:38has completed enrollment and well,
  • 28:40hopefully we'll get some information
  • 28:42regarding the results at some point soon,
  • 28:44so we can determine if there
  • 28:46is a benefit from this agent.
  • 28:47This is an anti veg F agent as well and
  • 28:51it was compared to placebo in patients
  • 28:53that have been previously treated with.
  • 28:56All standard chemotherapy,
  • 28:57and they may have received
  • 28:59regorafenib or lawn service,
  • 29:00or the combination.
  • 29:01Sorry,
  • 29:02but exposed to both of them in the past,
  • 29:04so it allowed all patients to participate in
  • 29:07the reason I also wanted to demonstrate this.
  • 29:11Show this to you is because in enrolled very
  • 29:14quickly earlier than the expected time frame,
  • 29:16and that's because it was such an unmet
  • 29:19need for our pretreated metastatic
  • 29:22colorectal carcinoma patients.
  • 29:24There is only one phase,
  • 29:26three ongoing trial at this time,
  • 29:28which is an international trial.
  • 29:30It's leap.
  • 29:31It's based upon this very small
  • 29:33study of originally 30 patients.
  • 29:35They have this small phase two study of
  • 29:3830 patients and they've now expanded it.
  • 29:40Based upon these results.
  • 29:41As you can see here,
  • 29:43basically 22% with a short PFS of 2.3
  • 29:46months and they've created this phase
  • 29:49three trial that is ongoing looking
  • 29:51at live at net plus pembrolizumab.
  • 29:54So I'm trying to identify another
  • 29:56potential option for patients and then
  • 29:59then patients will be considered compared.
  • 30:01Sorry to the standard of care
  • 30:03of regorafenib or lawn service,
  • 30:04so this is the only ongoing
  • 30:06phase three trial.
  • 30:07Currently enrolling and I'm sure it
  • 30:09will also finish enrolling quickly.
  • 30:11Hope I believe there's and hopefully
  • 30:14another couple of other trials
  • 30:16that are going to be open soon,
  • 30:19but currently when I last checked,
  • 30:21these were the only activated trials.
  • 30:24And I wanted to touch on rectal cancer,
  • 30:27'cause I think it's really important for
  • 30:29people to see where the field is going
  • 30:31and so traditionally for rectal cancer,
  • 30:35we had always provided neoadjuvant
  • 30:37chemotherapy with five,
  • 30:38a few based treatment,
  • 30:40and then proceeded to surgical
  • 30:42resection with the Tammy and then
  • 30:44followed by Advent chemotherapy.
  • 30:46Whether it's five,
  • 30:47a few based or oxaliplatin based,
  • 30:49but the reality was that a fair number
  • 30:52of patients were never receiving.
  • 30:54Our Advent chemotherapy,
  • 30:56either due to delays from surgical
  • 30:59resection due to toxicities or wound
  • 31:01healing issues or just lack of compliance
  • 31:05in regards to their actual treatment.
  • 31:08So what can we do to change this
  • 31:10aspect and in Europe they just
  • 31:11started looking at the sequence
  • 31:13and then in the United States.
  • 31:15We have followed suit and now it's
  • 31:17called total neoadjuvant therapy.
  • 31:18If you could potentially
  • 31:20provide all your treatment,
  • 31:21chemotherapy and your
  • 31:23chemo radiation therapy.
  • 31:24Up front before consideration of
  • 31:26surgical resection or the reverse
  • 31:29sequence where it chemo radiation
  • 31:31therapy followed by chemotherapy,
  • 31:33but I wanted to touch upon
  • 31:35this trial because it's
  • 31:36important that I do want to mention this
  • 31:38and the other reason is that obviously,
  • 31:41radiation therapy has known
  • 31:43toxicities and for our patients.
  • 31:46This is obviously an issue that
  • 31:47we do want to take into account,
  • 31:48so is there a way to reduce our
  • 31:51toxicities and is there a way potentially
  • 31:54to even avoid surgical resection?
  • 31:56So this is Angelita Habr Gama,
  • 31:59who at leave is in her late
  • 32:0180s at at this point,
  • 32:03and when she originally published
  • 32:06on the consideration of just
  • 32:09observing by close surveillance,
  • 32:12those patients that had had a
  • 32:14significant response to their treatment
  • 32:17instead of proceeding with TMA,
  • 32:19can you watch and wait?
  • 32:21Basically do a watch and wait approach
  • 32:23and watch them conservatively and when
  • 32:25she originally brought up this concept?
  • 32:27She herself as a surgeon.
  • 32:28People thought there was this
  • 32:30was this could not be possible.
  • 32:32This data was not real.
  • 32:35Why would a surgeon not offer a patient
  • 32:38surgical resection with rectal cancer?
  • 32:40And in fact, she appears to have caught up.
  • 32:43Obviously she was way ahead of her
  • 32:45time once again for this amazing idea.
  • 32:47So now we have some very interesting data
  • 32:51from the Memorial Sloan Kettering Group.
  • 32:53They created the Oprah trial,
  • 32:56the Oprah trial was a. Phase two study.
  • 32:58I don't want to emphasize.
  • 33:00This needs to be validated.
  • 33:02This is a phase two study done
  • 33:04that was completed at select sites.
  • 33:06I think about 15 to 18 sites
  • 33:09in low lying rectal tumors.
  • 33:11Providing the patients either chemo
  • 33:14radiation therapy followed by chemotherapy
  • 33:17or induction chemotherapy followed
  • 33:19by chemoradiation therapy and the
  • 33:22patients were evaluated by endoscopy and MRI.
  • 33:25If they had no complete response.
  • 33:28Then they went on to total
  • 33:31misso rectal excision,
  • 33:32or they had clinical response.
  • 33:35You could undergo watch and wait approach.
  • 33:39And here you can see regardless of
  • 33:41the sequence that you received,
  • 33:43there was equivalent disease free survival.
  • 33:46But he also noted, was those patients
  • 33:49once again low lying tumors.
  • 33:52Stage tumors stage three.
  • 33:54If you received chemo radiation
  • 33:56therapy first then followed by
  • 33:59chemotherapy for systemic therapy,
  • 34:01these patients appear to be more
  • 34:03likely to have sphincter preservation
  • 34:05and were more likely to undergo a
  • 34:07watch and wait approach because
  • 34:09of their degree of response.
  • 34:11Now this is phase two.
  • 34:13It is being.
  • 34:16Expanded more, not the exact same way,
  • 34:20but it is going to be a phase
  • 34:22three trial led by Josh Smith.
  • 34:24Also for Morris Sloan Kettering.
  • 34:25For consideration of this watch
  • 34:28and wait approach and once again
  • 34:31we need to validate the data.
  • 34:34Now they did update their
  • 34:35data just so you are aware.
  • 34:38At last year's ASCO and here's
  • 34:40pictures of clinical complete
  • 34:42response near complete response and
  • 34:44incomplete complete response and the
  • 34:46time frame of which they assessed.
  • 34:48When the response.
  • 34:49Sorry of the degree of response,
  • 34:50was roughly 7 to 8 weeks.
  • 34:53And here you can see when
  • 34:55looking at organ preservation,
  • 34:57obviously those that had a political
  • 34:59complete response at three years
  • 35:01that was 78% versus a near complete
  • 35:04response at three years was 45%.
  • 35:07So obviously there was possible there's
  • 35:10possibility of a watch and wait
  • 35:12approach for some of your patients.
  • 35:14Whenever we have this opportunity,
  • 35:16we review it with both our
  • 35:18radiation oncologists,
  • 35:19our surgical oncologists and our
  • 35:20medical oncologists and really make
  • 35:22this a multidisciplinary approach.
  • 35:23Then discuss it at our
  • 35:25multidisciplinary tumor board,
  • 35:26and I obviously encourage
  • 35:27everyone else to do the same.
  • 35:29So very intriguing.
  • 35:30Obviously we look forward
  • 35:31to the phase three trial.
  • 35:35And last but not least,
  • 35:37I do want to touch pad on something
  • 35:39very dear to me or early onset
  • 35:41colorectal cancer patients,
  • 35:42so this data is not new data.
  • 35:44This is looking at the senior
  • 35:47database from 1975 to 2010.
  • 35:48It was originally published by
  • 35:50Christina Bailey, who is actually
  • 35:51now my colleague here at Vanderbilt.
  • 35:53She wrote this when she was
  • 35:54a fellow at MD Anderson,
  • 35:55and as you can see here.
  • 35:59As you can see here, there is an
  • 36:02expected increase over the next decade
  • 36:04for our young patients in Blues,
  • 36:0620 to 34 years of age and
  • 36:08red is 35 to 49 years of age.
  • 36:11I'm sorry somebody has the wrong number.
  • 36:13I apologize and rectal cancer also
  • 36:16is supposed to be increased by the
  • 36:20year 2030 by 124% in the very young.
  • 36:22The 20 to 34 year age group.
  • 36:27This obviously was recognized
  • 36:29by patient advocates,
  • 36:30patients and their providers as well,
  • 36:32and this resulted in a change and
  • 36:34I think as many of you are aware
  • 36:37by the US preventive taskforce
  • 36:39to reduce our screening age from
  • 36:4150 years old to 45 years old,
  • 36:43and so this is a new recommendation.
  • 36:45Obviously if the patient is having symptoms
  • 36:47and it's younger than 45 years of age,
  • 36:50we would encourage screening immediately.
  • 36:54But this is an issue you can see here.
  • 36:57Trends in the United States looking at 2001
  • 36:59through 2005 versus a decade later on.
  • 37:02And you can see there's an increased
  • 37:04incidence of young onset colorectal cancer,
  • 37:06and especially in those states
  • 37:08with higher incidence of obesity.
  • 37:12This actually has been demonstrated
  • 37:14as well in the nurses health study.
  • 37:16Looking at your current BMI and
  • 37:18your risk of colorectal cancer.
  • 37:21And there's also been some interesting
  • 37:22data looking at the role of
  • 37:24antibiotic use and exposure and how
  • 37:25it may impact the microbiome.
  • 37:27This is one of roughly about three to four
  • 37:30studies that have been published as of late.
  • 37:32So intriguing data.
  • 37:33Once again,
  • 37:34we don't know the exact
  • 37:36reason why our young adults,
  • 37:37who the majority of them,
  • 37:39have spontaneous colorectal cancer.
  • 37:41They do not have Lynch syndrome or developing
  • 37:44colorectal cancer at such an early age.
  • 37:47So we had the honor of publishing a
  • 37:50picture paper recently in Lansing
  • 37:53Oncology looking at how to create
  • 37:55a framework for these patients.
  • 37:57As many of you know,
  • 37:57I'm I've created this young Adult
  • 38:00Cancer Center here at our institution,
  • 38:02which is not just for colorectal
  • 38:04cancer patients.
  • 38:05It's for all young adult cancer
  • 38:07patients between the ages of 20 and 45,
  • 38:09and these are some of the aspects
  • 38:10you really need to think about
  • 38:12when you're seeing these patients.
  • 38:13Fertility financial guidance,
  • 38:15physical wealth beating being.
  • 38:17Sorry.
  • 38:19But other concerns obviously
  • 38:22regarding job security,
  • 38:25body image and just the fear of not
  • 38:29knowing exactly how best to address this,
  • 38:31because these individuals are very
  • 38:33young and they're going through
  • 38:35a very different aspect of their
  • 38:38life versus our older median age
  • 38:40patient of 67 years old.
  • 38:41In addition, we you know,
  • 38:44as you can guess,
  • 38:45these patients face other concerns,
  • 38:47especially regarding financial
  • 38:48toxicities and and the the pressure
  • 38:51that they feel because some of them
  • 38:54obviously are still working and
  • 38:56don't have financial independency.
  • 38:59They're not financially independent,
  • 39:01but they don't have to worry
  • 39:03about the cost of care,
  • 39:04and so these are important things
  • 39:06to take into account for our
  • 39:08young adult patient population.
  • 39:09So here are my Co directors.
  • 39:11I just wanted to highlight that
  • 39:12Michael Byrne and Libby Davis.
  • 39:14Michael Byrne is BMT,
  • 39:16and Libby Davis in sarcoma.
  • 39:18And this is just the information on
  • 39:20our program and we're very grateful to
  • 39:22have many involved in our group and
  • 39:25provide resources for our patients.
  • 39:26And this was actually one of my patients.
  • 39:29She was 32.
  • 39:32And you know,
  • 39:32I love it when people say,
  • 39:33well, you look too healthy.
  • 39:34You can't have colorectal cancer.
  • 39:36Well, she was training for a
  • 39:38marathon and she was in great
  • 39:40health but had bowel issues,
  • 39:42probably for about 8 months.
  • 39:44They kept in telling her
  • 39:46that she had irritable bowel
  • 39:48disease or it was hemorrhoids,
  • 39:50or it's from her marathon training.
  • 39:53And when I saw her she had about 50 to
  • 39:5760% of her liver involved with tumor.
  • 39:59Unfortunately, she as you can see here.
  • 40:02She fought for with her basically
  • 40:05was amazing individual thought
  • 40:08her colorectal cancer.
  • 40:11Lived with it for about five years
  • 40:14and unfortunately passed away
  • 40:16the latter part of last year,
  • 40:17but during her time she made a
  • 40:19huge effort to serve an advocacy
  • 40:21groups and became a national patient
  • 40:23advocate for the fight colorectal
  • 40:25cancer program and that was actually
  • 40:27a picture of her in Times Square and
  • 40:30she used to run regularly these 5K
  • 40:33events with her friends walk run.
  • 40:36So in closing points,
  • 40:37Please remember screening starts
  • 40:39at the age of 45.
  • 40:41Please continue to educate others
  • 40:42about the signs and symptoms of
  • 40:44colorectal cancer and recognize
  • 40:45that these patients may need to be
  • 40:47screened earlier than 45 if they have
  • 40:49these symptoms that do not resolve,
  • 40:51recognize the unmet needs are so
  • 40:54psychosocial needs of our patients.
  • 40:56Currently,
  • 40:56most of the advances in colorectal
  • 40:58cancer have largely been made in
  • 41:01the rare molecular subtypes and
  • 41:02for the majority of our patients.
  • 41:04We still need novel agents
  • 41:05and unfortunately for us.
  • 41:06Colorectal cancer IO therapy has
  • 41:08had limited efficacy excluding
  • 41:10in MSI high patients.
  • 41:12Next generation sequencing is always
  • 41:13the standard of care for our patients,
  • 41:15and I always,
  • 41:16always,
  • 41:16always try to enroll to a clinical trial
  • 41:18whenever possible so we can obviously
  • 41:21make greater treatment advances.
  • 41:22So thank you so much for your
  • 41:24attention and I would be happy
  • 41:26to take any questions.
  • 41:30Kathy, that was great.
  • 41:31I didn't talk to you fast.
  • 41:33No no, no no. It was perfect and
  • 41:36it was incredibly informative
  • 41:38and really just wonderful.
  • 41:40I think Nita may have the first question.
  • 41:48Thank you Kathy, and thanks Eric.
  • 41:50I ask Doctor Wyner,
  • 41:52mentioned really informative and and
  • 41:54taking us through where the field is.
  • 41:57Perhaps my first question to you is
  • 41:59more around rectal cancer management.
  • 42:02And as you mentioned,
  • 42:03at the end of the hammer,
  • 42:05gamedata and watchful waiting and I
  • 42:08think the early trial on neoadjuvant.
  • 42:10I think part of the worry there is are you?
  • 42:12How are you all accounting in this
  • 42:14you know is around this field where
  • 42:17there's not only a biological?
  • 42:18Implications, but.
  • 42:20Quality of life implications.
  • 42:22That is, do you miss the window on a
  • 42:25curative approach without an ostomy and
  • 42:27and and I wonder if that was considered,
  • 42:30especially in that first trial,
  • 42:31which I thought was.
  • 42:34Interesting that people at
  • 42:35Memorial agree to do that to
  • 42:37put in Check Point early on.
  • 42:39And because you may lose a window and I
  • 42:41wonder where you think the field is on that.
  • 42:43And then I have a bigger question.
  • 42:45Perhaps around colon cancer,
  • 42:47I think because number one in rectal cancer,
  • 42:51you know as as I showed you,
  • 42:53the incidence is expected to be
  • 42:55quite higher over the next decade,
  • 42:57especially for our young patients.
  • 42:59So from my own personal experience,
  • 43:02when I'm seeing these patients a lot of
  • 43:04them are willing to take that risk because
  • 43:06especially if they have a low lying tumor,
  • 43:09they don't want to consider an APR,
  • 43:12and so they're willing to consider that risk
  • 43:15as long as they're being followed closely,
  • 43:18and many of them are extremely compliant,
  • 43:20then in that setting.
  • 43:21So I think that in that case,
  • 43:23as long as they have a good relationship
  • 43:25with their surgical oncologist and
  • 43:28medical oncologist, I think it's
  • 43:30very reasonable to consider it in.
  • 43:31In that setting, you know.
  • 43:32Obviously what I didn't show you is that.
  • 43:34No one really looked at the role of
  • 43:36circulating tumor DNA in this setting, right?
  • 43:38But in the phase three trial, that's I.
  • 43:41I don't know, I presume won't be
  • 43:43open for another 8 to 10 months.
  • 43:45I hope they will also take that into account,
  • 43:48and I think other trials are also
  • 43:49trying to take that into account.
  • 43:51And obviously 'cause that could impact
  • 43:53our surveillance period as well.
  • 43:55But I agree with you,
  • 43:56you know,
  • 43:57recurrent rectal cancer is one of the
  • 43:59most challenging cancers because of the
  • 44:02quality of life on patients because.
  • 44:05Lost largely the involvement of the sacrum,
  • 44:08when they have recurrent disease
  • 44:10in the pain that means do.
  • 44:12But I I it's very interesting when you talk
  • 44:14to the national patient advocacy groups,
  • 44:17you know,
  • 44:17once you get a large number
  • 44:19of them are younger patients,
  • 44:20they are more than willing to take
  • 44:22that risk to avoid the potential
  • 44:24issues with bowel bowel issues to avoid
  • 44:27even radiation therapy in the setting
  • 44:29of the MSI high patient population
  • 44:32because of toxicities as well.
  • 44:34So they're really looking at quality of life.
  • 44:37The majority of them,
  • 44:38no,
  • 44:38I think
  • 44:39they're the ones that are low and you
  • 44:41can avoid a stoma. They'll do it.
  • 44:42I think the ones where the worry
  • 44:44is is it's perhaps an LAR.
  • 44:45And now you're dooming them
  • 44:47to a recurrence and Eric will
  • 44:49remember this in the late 90s.
  • 44:51We were doing local excisions for T2T3,
  • 44:53and then they were coming back with a APR.
  • 44:56So I think that that perhaps is the part.
  • 45:00That, I think would be a concern,
  • 45:02and I think Brazilian data they
  • 45:04follow their patients really closely,
  • 45:06whereas we're not as as a
  • 45:08coordinated system in America.
  • 45:11And and you have a very valid point,
  • 45:12but but patients are really motivated.
  • 45:17Can I ask just a little question before
  • 45:19you get to your big question needed?
  • 45:20And my little question is.
  • 45:23How do you you know?
  • 45:24So I understand you follow people closely,
  • 45:27but. How do you follow people closely?
  • 45:31I mean you can't.
  • 45:32You can't be biasing multiple
  • 45:34little areas all the time,
  • 45:36so you're following people closely with just,
  • 45:40you know, some sort of scoping.
  • 45:43You know, a low scoping procedure,
  • 45:45correct? We kind of followed
  • 45:46at our institution.
  • 45:47We kind of followed the memorial
  • 45:50data and have also done the
  • 45:53regular intervals with endoscopy.
  • 45:55Testing as well as diagnostic
  • 45:58imaging with MRI.
  • 46:00Yes Nita yeah no. I think
  • 46:03Eric you hit the knee.
  • 46:03I think who is examining
  • 46:05and do they pay attention?
  • 46:06I think that's the set.
  • 46:07The second question perhaps is
  • 46:09similar now that you know if you're
  • 46:11looking at breast and standardization,
  • 46:13I'd still sense that even though colorectal
  • 46:16cancer is one of our most common cancers,
  • 46:18there remains a gap in standardized
  • 46:21testing and you just showed U.S.
  • 46:23data of the 1% rule, right?
  • 46:25The one person you know,
  • 46:26the 3% hurt to the MSI.
  • 46:28And how do we sort of work in
  • 46:31national agencies in your role in?
  • 46:33Starting to think about cancer and what
  • 46:35should be the major things we test.
  • 46:37I I still think it's a Wild West out there.
  • 46:40If we ignore some of the top
  • 46:42institutions you know when you
  • 46:43get to the rest of the country
  • 46:44I I would say that.
  • 46:46From my experience thus far,
  • 46:48I would say the majority of people
  • 46:50do get tested for obviously rash.
  • 46:52That has been the most common thing which,
  • 46:53which obviously is extremely important.
  • 46:55So then they can avoid
  • 46:57anti EGFR therapy there.
  • 46:58I fully agree with you though there
  • 47:01are patients that still come to me
  • 47:03that have never had the raft testing,
  • 47:05which obviously is extremely important.
  • 47:06They've never had MSI testing and
  • 47:09you know I fully agree with you.
  • 47:11I would just say that in every
  • 47:14single lecture we give every single.
  • 47:17Bit of publications that we can provide
  • 47:19to individuals to educate others.
  • 47:22We have to encourage that all patients need
  • 47:25to be tested for molecular marker analysis.
  • 47:28I mean, that is critical to their
  • 47:31overall treatment and and you know
  • 47:34it's it's so interesting when bearoff.
  • 47:37So when Scott Kopetz originally
  • 47:40talked about testing for BRAF,
  • 47:42everybody thought he was crazy because
  • 47:44it was such a rare patient population.
  • 47:47And how we're going to get people to do that,
  • 47:49but it's really as you know,
  • 47:51it's a matter of education.
  • 47:53And now it's it's.
  • 47:54It's for the majority people.
  • 47:56It is considered a standard of care.
  • 47:57I would say a large number
  • 47:59of people test for it now,
  • 48:00but her two is still.
  • 48:02It's still, you know,
  • 48:03we're trying to get there,
  • 48:05but her two is not commonly tested for,
  • 48:08and Kathy does that affect treatment
  • 48:10for stage one and stage two disease no?
  • 48:13So, I mean, you're really talking
  • 48:15about more advanced disease.
  • 48:16We're testing is really.
  • 48:17Critical, correct?
  • 48:18Although obviously for MSI high we
  • 48:21would encourage it in all stages.
  • 48:23Yes, for largely metastatic
  • 48:25disease 'cause we have not found
  • 48:27benefit of these other targeted
  • 48:29agents in early stage disease.
  • 48:32We've tried.
  • 48:34With anti EGFR therapy,
  • 48:36we've tried with anti VEGF
  • 48:38therapy and stage three,
  • 48:40which was they were
  • 48:41not successful studies.
  • 48:43OK, so I'm going to ask a question.
  • 48:47That you know, sort of a like big
  • 48:50question about the future or the present.
  • 48:53But if you had could do anything.
  • 48:57And the goal is to reduce colon cancer
  • 49:01deaths in the United States and beyond.
  • 49:03And you have two interventions
  • 49:06that you could use.
  • 49:08What would you do?
  • 49:10Two interventions or two interventions
  • 49:12or two two? You know?
  • 49:14What are the unmet needs so
  • 49:16the two biggest unmet needs
  • 49:18for colorectal cancer in 2022?
  • 49:21I would say, well, the the number
  • 49:23one needs still remains screening.
  • 49:25I mean, in all fairness, we are still
  • 49:27under screening in the United States.
  • 49:30It's still I think it's like 78 percent is
  • 49:33the best so so many people are being missed.
  • 49:36And just because they don't
  • 49:38want to be screened. Number 20.
  • 49:41If I could do something
  • 49:44and make it effective,
  • 49:46I wish we could find some way to make IO
  • 49:49therapy helpful in the majority of her MSI.
  • 49:52Stable colorectal cancer patients.
  • 49:54We appear to be at a standstill in regards
  • 49:59to any potential combination thus far.
  • 50:02It you know it has.
  • 50:04It's worked well in other malignancies.
  • 50:06Obviously, Upper GI, HTC Cholangio,
  • 50:11and here we are still nowhere with it,
  • 50:13really.
  • 50:13In colorectal cancer,
  • 50:14except the less than 5% with MSI HIGH.
  • 50:17But screening I would rather prevent the
  • 50:20colorectal cancer and not have to treat it.
  • 50:23That would be my number one
  • 50:24thing which I know sounds odd
  • 50:25coming as a medical oncologist.
  • 50:29Well look look, we all want to put
  • 50:31ourselves out of work eventually
  • 50:33and to what extent do health care
  • 50:35disparities lay in tech excess
  • 50:37debts in colorectal cancer?
  • 50:41So obviously this isn't.
  • 50:43This is an issue as you
  • 50:46know in our clinical trials.
  • 50:48As like many other clinical trials,
  • 50:50especially though in colorectal cancer,
  • 50:53the majority of patients that enroll in
  • 50:55clinical trials are not our average patients,
  • 50:5895% are of their Caucasian or white,
  • 51:02and the majority of patients do not
  • 51:04participate in clinical trials.
  • 51:06I wish I could.
  • 51:07So if the number if I could ask,
  • 51:08have a number three, I would get,
  • 51:10I would get more people to appreciate
  • 51:13the importance of clinical trials
  • 51:16and to help with enrollment,
  • 51:17and allow us to be able to provide.
  • 51:19The standard treatment arm in the
  • 51:21community you know and and that
  • 51:24way will help with enrollment,
  • 51:25so that would be my number three thing,
  • 51:27but in regards to diversity we are
  • 51:31lacking in clinical trials completely,
  • 51:34and a large number of the obviously
  • 51:36the datasets that exist.
  • 51:37So I love Andrea sirsak.
  • 51:39She's a friend of mine memorial,
  • 51:40but she just published a big publication
  • 51:42looking at mutations at Memorial.
  • 51:44It's one of the largest data sets,
  • 51:46but yet 95% of her patients.
  • 51:50Or white,
  • 51:50and so it's not representative
  • 51:52of the actual community.
  • 51:53Nothing against her.
  • 51:54It's the data she has,
  • 51:55but that's the patient population
  • 51:57that they have at Memorial.
  • 52:00The problem, so we have a kitten
  • 52:02question from Mary Kate Kelly,
  • 52:03and that question is,
  • 52:04there's a low fat diet or a
  • 52:07vegetarian diet help decrease
  • 52:08the chance of colorectal cancer.
  • 52:11I would say definitely does not hurt.
  • 52:13There's a lot of literature
  • 52:15going back and forth.
  • 52:17We're going in the diet.
  • 52:17I think the majority of studies have shown.
  • 52:20Obviously your tendency to
  • 52:22obesity is is more of a concern.
  • 52:27There was also a very very nice publication
  • 52:29just recently from my colleague here,
  • 52:31Martha Shrubsall and epidemiology looking at.
  • 52:36Poly phenols, I believe.
  • 52:39And the increased risk actually
  • 52:42in the black patient population
  • 52:45which was published just recently.
  • 52:48And a related question just came in,
  • 52:52which is in patients who
  • 52:53have had colorectal cancer,
  • 52:55and they say to you,
  • 52:57what can I do to prevent a recurrence?
  • 52:59Are there any data that would
  • 53:02support lifestyle interventions
  • 53:04such as exercise, diet,
  • 53:06any any other sort of
  • 53:09nutritional supplements,
  • 53:11and finally, aspirin.
  • 53:13Right, so there is data regarding aspirin
  • 53:17that appears to be more beneficial in
  • 53:20the PIK 3 CA mutation patient which
  • 53:24is about 15 to 20% of our patients.
  • 53:26Better baby aspirin seems to be fairly
  • 53:29benign and potentially helpful.
  • 53:30And then Jeff Meyer Heart has published
  • 53:33before on the role of exercise as well.
  • 53:36I would say all good healthy eating
  • 53:39patterns and exercise obviously can't harm
  • 53:42you and I would highly recommend them.
  • 53:45And then there's been some.
  • 53:48I would say those those the majority
  • 53:50of the data.
  • 53:53Alright, well, and and any data on vitamin D
  • 53:59that is an ongoing trial being led
  • 54:02by Kim Eing I think it is called
  • 54:05forgot the name of the trial.
  • 54:06I apologize, it is being run through the
  • 54:09alliance and so they are looking at that.
  • 54:12Alright, well I think that I think everyone
  • 54:15got a tremendous amount out of this.
  • 54:17Thank you so much for joining us all,
  • 54:19be it from a distance we we look forward
  • 54:22to having you here in person at some time.
  • 54:25And please please give our best to all
  • 54:28our friends at Vanderbilt and we really
  • 54:31enjoyed having you thank you so much.
  • 54:32Thank you so much. It's been my pleasure.
  • 54:34It's been great thanks. Have a great day.