Necitumumab, a human immunoglobulin G1 anti-EGFR monoclonal antibody, added to standard chemotherapy significantly improved survival compared with chemotherapy alone as first-line treatment of patients with stage IV non–small-cell lung cancer (NSCLC) of squamous histology.
The median overall survival (OS) was extended by 1.6 months in patients randomized to the arm receiving necitumumab plus gemcitabine and cisplatin in the phase 3 clinical trial, said Nick Thatcher, MD, PhD, Professor in Medical Oncology, University of Manchester, Christie Hospital NHS Foundation Trust, United Kingdom, at ASCO 2014.
Although the results were criticized because of the less-than-2-month improvement in survival, Dr Thatcher remarked, “It’s the first time that we’ve seen benefit in this group of patients over the last 20 or 25 years.”
Progress in the treatment of squamous NSCLC has been minimal over the past 2 decades compared with nonsquamous NSCLC, noted Dr Thatcher. The main reason is the lack of relevant oncogenic drivers to inform treatment decisions. Necitumumab was chosen as an add-on to standard gemcitabine plus cisplatin because EGFR expression is detectable in most advanced squamous NSCLC tumors.
The open-label multicenter study randomized 1093 patients with stage IV squamous NSCLC to gemcitabine 1250 mg/m2 on days 1 and 8 and intravenous cisplatin 75 mg/m2 on day 1 plus necitumumab 800 mg on days 1 and 8, or to gemcitabine plus cisplatin alone, administered every 21 days for up to 6 cycles.
Patients assigned to gemcitabine plus cisplatin and necitumumab who had no disease progression continued to receive necitumumab alone until disease progression or intolerable toxicity. Overall, 51% of the patients randomized to necitumumab plus chemotherapy continued to receive necitumumab monotherapy for a median of 4 additional cycles.
The primary end point, median OS, was 11.5 months in the arm receiving necitumumab plus chemotherapy versus 9.9 months in the arm receiving chemotherapy alone (P = .012). The 1-year survival rate was 47.7% and the 2-year survival rate was 19.9% in the necitumumab plus chemotherapy arm compared with 42.8% and 16.5%, respectively, in the chemotherapyalone arm.
The median progression-free survival (PFS) was extended from 5.5 months in the chemotherapy arm to 5.7 months in the necitumumab plus chemotherapy arm (P = .02).
The need for systemic therapy after the study was similar in the 2 treatment groups: 47.3% in the necitumumab plus chemotherapy arm versus 44.7% in the chemotherapy-alone arm.
A preplanned exploratory analysis of the EGFR H-score, a potential predictive biomarker, using a prespecified cut point of 200, showed no association between it and the OS or PFS by cut-point interaction.
Adverse event rates leading to the study discontinuation were 31.2% in the necitumumab plus chemotherapy arm and 24.6% in the chemotherapy-alone arm; adverse event rates leading to death were 12.3% and 10.5%, respectively. Grade ≥3 adverse events that occurred significantly more often in the necitumumab arm were hypomagnesemia (9.3% vs 1.1%, respectively), skin rash (7.1% vs 0.4%, respectively), and venous thromboembolic events (5% vs 2.6%, respectively).
Although statistically significant, the improvement in OS did not meet ASCO’s threshold for a clinically meaningful difference of 2.5 months to 3 months in squamous NSCLC, noted Julie R. Brahmer, MD, Associate Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore.