Prognosis for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation of EGFR and designed a phase 2 trial of chemotherapy, cetuximab and erlotinib in patients with R/M HNSCC.

24 patients were enrolled and treated with carboplatin, paclitaxel and cetuximab administered in 21-day cycles. Erlotinib was added with cycle 2. Primary end point was objective response rate (ORR). Secondary end points were toxicity, overall survival (OS) and laboratory correlates.

Median age was 65.5 years. Median duration on treatment was 4.6 months. ORR with cycle 1 of treatment was 33.3%, and for cycle 2 and beyond was 62.5%. Median progression-free survival (PFS) was 6.2 months, and median OS was 10.6 months. Most common treatment-related adverse events included anemia, neutropenia, skin rash, diarrhea, and hypomagnesemia.

Dual EGFR blockade was tolerable and efficacious in this small patient sample. With an ORR of 62.5%, the study met its primary endpoint. PFS and OS were comparable to historical controls. Dual EGFR targeting without the chemotherapy backbone is worthy of further study.

Clinical trial information: NCT01316757. Study registered March 8th, 2011

Dr. Bhatia has research funding from Boehringer-Ingelheim and Genentech. She has received consulting fees from Daiichi-Sankyo. Dr. Bauman has received consulting fees from Pfizer and EMD Serono Dr. Rimm has served as an advisor for Astra Zeneca, Cell Signaling Technology, Cepheid, Daiichi Sankyo, Danaher, Halda Therapeutics, Incendia, Nucleai, PAIGE.AI, and Sanofi. Astra Zeneca, Cepheid, Konica Minolta, Leica, NavigateBP, NextCure, Nanostring, and Lilly, have funded or currently fund research in his lab Other authors declare no relevant conflicts.

NCT01316757

Genentech

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted according to the International Conference on Harmonization E6 Guideline for Good Clinical Practice (GCP) and the Declaration of Helsinki. IRBs of all participating institutions (Yale Cancer Center, Fox Chase Cancer Center and University of Texas Southwestern) approved the study. All enrolled patients signed the IRB approved informed consent before study assessments were performed and treatment was administered.

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