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Yale Trial Validates Immunotherapy Treatment for Non-Small Cell Lung Cancer

September 30, 2020

The immunotherapy drug atezolizumab improves survival over standard chemotherapy for many patients with newly diagnosed non-small cell lung cancer (NSCLC), according to a new study led by Yale Cancer Center (YCC) researchers. The findings, from a global randomized phase 3 clinical trial published today in the New England Journal of Medicine, support the U.S. Food and Drug Administration’s approval of the drug for this indication in May.

“These are exciting results that could be life-changing for many patients,” said Roy S. Herbst, MD, PhD., Chief of Medical Oncology at YCC and Smilow Cancer Hospital, Associate Cancer Center Director for Translational Research at YCC, and lead author of the study. “Lung cancer is the most common cancer worldwide, with more than 1.5 million patients diagnosed each year. Half of patients are diagnosed with metastatic disease and they could be a candidate for this drug.”

Atezolizumab is a “checkpoint inhibitor” drug designed to help immune system cells called T cells destroy cancer. The drug targets a protein known as PD-L1 on the surface of tumor cells, which can signal T cells not to attack, so stopping this signaling can unleash the T cells against cancer.

The trial enrolled 554 patients with stage 4 metastatic NSCLC tumors that lacked mutations in the EGFR or ALK genes (since tumors with those mutations are better treated by other drugs). Among 205 patients whose tumors displayed high expression of PD-L1, the median overall survival was 20 months for those given atezolizumab and 13 months for those who received standard platinum-based chemotherapy. Median progression-free survival rose to eight months for participants given atezolizumab versus five months for those on chemotherapy.

“Also encouraging is that atezolizumab was generally well tolerated,” said Herbst. “Side effects for patients were similar to those seen in other trials of the drug, which has been approved for treatments of several types of cancer.”

The trial also analyzed how atezolizumab performed versus chemotherapy among people whose blood showed markers of high tumor mutational burden—high levels of genetic mutations in scraps of cancer DNA that circulate in the blood. In some types of cancers, tumor mutational burden correlates with better response to immunotherapy.

“Among these patients with NSCLC, those with high tumor mutational burden who received atezolizumab showed improved progression-free survival of seven months versus four months for those given chemotherapy,” said Herbst. “This finding suggests that the biomarker should be explored further.”

Atezolizumab is the first PD-L1 inhibitor shown to beat chemotherapy as a first-line monotherapy among people with NSCLC. Pembrolizumab, an agent that inhibits the PD-1 protein on the surface of T cells to which PD-L1 binds, was approved previously for this indication.

Yale scientists led the first phase one clinical trial of atezolizumab in this population in 2012 and moved the drug candidate all the way to the global phase 3 trial. Ongoing clinical studies are now analyzing combinations of atezolizumab with other drugs to treat people with NSCLC.

Co-authors on the paper include Giuseppe Giaccone of the Weill Cornell Medical Center; Filippo de Marinis of the European Institute of Oncology; Niels Reinmuth of the Asklepios Lung Clinic; Alain Vergnenegre of the University Hospital Limoges; Carlos Henrique Barrios of the Hospital São Lucas; Masahiro Morise of Nagoya University; Enriqueta Felip of the Vall d’Hebron University Hospital; Zoran Andric of the Bezanijska Kosa Clinical Hospital Center; Sarayut Geater of Prince of Songkla University; Mustafa Özgüroğlu of Istanbul University; Wei Zou, Alan Sandler, Ida Enquist, Kimberly Komatsubara, Yu Deng, Hiroshi Kuriki, Xiaohui Wen, Mark McCleland and Simonetta Mocci of Genentech; and David Spigel of the Sarah Cannon Research Institute/Tennessee Oncology.

Funding was provided by Genentech.

Submitted by Anne Doerr on September 30, 2020