Dual EGFR Inhibition Improves Response in Head and Neck Cancer

This study examined whether adding a drug called erlotinib to standard treatment would improve outcomes for patients with a type of cancer known as metastatic or recurrent squamous cell carcinoma of the head and neck (HNSCC). Erlotinib is a type of medication that targets the epidermal growth factor receptor (EGFR), which is often overactive in these cancers. The researchers aimed to see if this combination could enhance the effectiveness of treatment and address resistance issues seen with current therapies.

HNSCC is a serious condition affecting many individuals worldwide, with limited treatment options and poor survival rates. Improving treatment effectiveness is crucial for increasing survival and quality of life for these patients. This research could lead to new therapy combinations that offer better outcomes, providing hope for those with this challenging cancer type.

The researchers conducted a phase II clinical trial involving 24 patients with metastatic or recurrent HNSCC. Patients received a treatment regimen that included chemotherapy drugs (carboplatin and paclitaxel), an antibody called cetuximab, and, starting with the second treatment cycle, erlotinib. The main goal was to measure the objective response rate (ORR), which reflects the percentage of patients whose cancer shrinks or disappears after treatment. They also assessed side effects, survival rates, and conducted laboratory tests to understand the biological effects of the treatment.

The study found that adding erlotinib increased the ORR from 33.3% in the first cycle to 58.3% in subsequent cycles. Median progression-free survival (the time patients lived without the cancer worsening) was 6.2 months, and median overall survival was 10.6 months. The treatment was effective but came with side effects, such as anemia, skin rash, and diarrhea. Despite these side effects, the combination therapy showed promise in overcoming some resistance mechanisms of current treatments. On-study biopsies performed in eight patients showed that the addition of erlotinib reduced EGFR expression below levels achieved by cetuximab, and that erlotinib also impaired nuclear EGFR functions.

These findings suggest that dual targeting of EGFR with cetuximab and erlotinib could be a viable strategy to improve treatment outcomes for HNSCC patients. It highlights the potential of this combination therapy to enhance response rates, although the impact on long-term survival requires further investigation. This approach could inform future treatment strategies and clinical trials.

The researchers suggested further studies to explore dual EGFR targeting without chemotherapy, as well as investigations into biomarkers that could help identify patients who would benefit most from this treatment. They are also conducting another trial with a different EGFR inhibitor to refine and optimize treatment strategies for this patient population.

This research was supported by Yale University.