CHICAGO, IL—Adding necitumumab to gemcitabine-cisplatin significantly improved overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) in the first-line treatment of patients with stage IV squamous non-small cell lung cancer (NSCLC), the largest randomized phase 3 study in this population concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Necitumumab, also known as IMC-11F8/LY3012211, is a human IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody that inhibits ligand-binding and receptor activation, said Nick Thatcher, MB, BChir, PhD, at The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom. “EGFR is detectable in the vast majority of advanced squamous NSCLC tumors,” he said, adding that this histology comprises 25% to 30% of all cases of NSCLC.

When compared with nonsquamous NSCLC, progress in treating squamous NSCLC has been limited over the past two decades, primarily due to lack of relevant oncogenic drivers to inform treatment decisions. When cetuximab was added to platinum-based first-line therapy for NSCLC, efficacy improved significantly, with the highest benefit shown in the squamous subpopulation. For that reason, the SQUIRE study was initiated, combining necitumumab with gemcitabine-cisplatin chemotherapy, which is considered a standard of care in patients with advanced or metastatic squamous NSCLC, Dr. Thatcher explained.

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The multicenter open-label study randomly assigned 1,093 patients to gemcitabine 1250 mg/m² days 1 and 8 and cisplatin 75 mg/m² day 1 plus necitumumab 800 mg days 1 and 8 (n=545) or gemcitabine/cisplatin (n=548) every 21 days for up to six cycles. Patients in the gemcitabine-cisplatin plus necitumumab arm without disease progression continued on necitumumab alone until progression or intolerable toxicity. Primary endpoint was OS, with PFS, objective response rate (ORR), and safety as secondary endpoints. Although patient selection was not based on EGFR protein expression, levels were explored by immunohistochemistry in tumor tissue.

Males comprised the majority of both treatment arms (83% in the necitumumab arm vs. 84% in the chemotherapy-alone arm), as did Caucasians (84% vs. 83%); the majority were also smokers (92% vs. 90%). Patients were primarily Eastern Cooperative Oncology Group (ECOG) performance status 0/1 (91% in both arms), with the lung as the primary metastatic site (83% in both arms). Of the patients in the triple combination therapy arm, 51% continued necitumumab alone for a median of four additional cycles.

Dr. Thatcher reported that the addition of necitumumab to gemcitabine-cisplatin significantly improved OS (hazard ratio [HR], 0.84; 95% CI: 0.74-0.96, P = 0.012); median OS was 11.5 months (95% CI: 10.4-12.6) versus 9.9 months (95% CI: 8.9-11.1).