Adding necitumumab to standard of care with gemcitabine-cisplatin improves survival compared with chemotherapy alone as first-line treatment in patients with stage IV nonâ€“small cell lung cancer (NSCLC) of squamous histology.
Nick Thatcher, MB, BChir, PhD
Adding necitumumab, a fully human IgG1 anti-EGFR monoclonal antibody, to standard of care with gemcitabine-cisplatin improves survival compared with chemotherapy alone as first-line treatment in patients with stage IV nonsmall cell lung cancer (NSCLC) of squamous histology.
Data from the phase III SQUIRE trial demonstrated an improvement in median overall survival (OS) of 1.6 months in patients randomized to the necitumumab plus gemcitabine-cisplatin arm of the study, said Nick Thatcher, MB, BChir, PhD. Study results were presented at the 2014 ASCO meeting.
“It’s important to remember that we’re dealing with squamous cell lung cancer. The SQUIRE results are important in the search for a new treatment for patients with metastatic squamous lung cancer,” he said. “It’s the first time that we’ve seen benefit in this group of patients over the last 20 or 25 years.”
Squamous histology accounts for 25% to 30% of NSCLC but progress in its treatment over the past two decades has been limited when compared with nonsquamous histology, leaving prognosis poor, notes Thatcher, professor of oncology, University of Manchester, Christie Hospital NHS Trust in Manchester, United Kingdom.
As gemcitabine-cisplatin represents the current standard of care in patients with advanced or squamous NSCLC, it was chosen as the backbone therapy in SQUIRE. Necitumumab was chosen as add-on therapy because EGFR is detectable in the vast majority of advanced squamous NSCLC tumors.
In the multicenter study, 1093 patients with pathologically proven stage IV squamous NSCLC were randomized to gemcitabine, cisplatin, and necitumumab (n = 545) or gemcitabine-cisplatin alone (n = 548) for up to 6 cycles. In each 21 day cycle, gemcitabine was administered at 1250 mg/m² on days 1 and 8 and cisplatin at 75 mg/m² on day 1. Patients received necitumumab at 800 mg IV on days 1 and 8.
Patients assigned to gemcitabine-cisplatin plus necitumumab with no disease progression continued on necitumumab alone until progressive disease or intolerable toxicity. Patient selection was not based on EGFR protein expression, but EGFR levels were explored by immunohistochemistry in tumor tissue.
“This was a heavily metastatic population, with more than 2 sites of disease in over 50% of the patients,” said Thatcher.
Fifty one percent of patients randomized to necitumumab plus chemotherapy continued necitumumab monotherapy for a median of 4 additional cycles.
The primary endpoint, median OS, was 11.5 versus 9.9 months in favor of necitumumab, representing a hazard ratio (HR) of 0.84 (P= .012). The 1-year survival rates were 47.7% and 42.8%, and the 2-year survival rates were 19.9% and 16.5% in the necitumumab/chemotherapy and chemotherapy alone arms, respectively.
Necitumumab plus gemcitabine and cisplatin was associated with a significant improvement in progression-free survival (PFS; HR = 0.85;P= .02). Median PFS was 5.7 versus 5.5 months, respectively.
A prespecified subgroup analysis of OS demonstrated a consistent treatment effect, including in patients with ECOG performance status 2.
The overall response rate was 31.2% in the necitumumab plus gemcitabine-cisplatin arm compared with 28.8% in gemcitabine-cisplatin arm. However, this was deemed to be a nonsignificant difference (P= .40). The disease control rate, defined as the rate of complete response, partial response, and stable disease, was significantly superior with the addition of necitumumab to chemotherapy (82% vs 77%;P= .043).
The need for post-study systemic therapy was similar in the 2 treatment groups; 47.3% in the necitumumab plus chemotherapy arm received further therapy compared with 44.7% in the chemotherapy alone arm.
The preplanned exploratory analysis of the EGFR H score using the prespecfied 200 cutoff showed no treatment-by-cutoff interaction, suggesting the lack of a clear biomarker.
The rates of grade ≥3 adverse events were 72.1% in the necitumumab/chemotherapy arm versus 61.6% in the chemotherapy alone arm. Adverse events leading to discontinuation of treatment occurred at a rate of 31.2% in the necitumumab/chemotherapy arm and 24.6% in the chemotherapy alone arm, and the incidences of adverse events with an outcome of death were 12.3% and 10.5%, respectively. There was no increase in hematologic toxicity with the addition of necitumumab. Grade ≥3 adverse events that occurred significantly more often in the necitumumab/chemotherapy arm were hypomagnesemia (9.3% vs 1.1%), skin rash (7.1% vs 0.4%), and venous thromboembolic events (5.0% vs 2.6%).
Thatcher N, Hirsch FR, Szczesna A, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC).J Clin Oncol. 2014;32:5s (suppl; abstr 8008).