In the SQUIRE study, patients with metastatic squamous non–small-cell lung cancer (NSCLC) were randomized to receive up to 6 cycles of gemcitabine plus cisplatin (GC; gemcitabine: 1250 mg/m2 IV, days [d] 1 and d8; cisplatin: 75 mg/m2 IV, d1) either with or without necitumumab (800 mg IV, d1 and d8). Patients who were randomized to GC plus necitumumab (GC + N) who did not progress continued necitumumab until progressive disease (PD) or unacceptable toxicity.
The study, which included mandatory tissue collection, assessed EGFR protein expression in a central lab. Patients who were EGFR-positive, received 4 or more cycles of GC, and did not experience PD were included in this analysis.
Among SQUIRE’s intent-to-treat (ITT) population of 1093 patients, 90% had evaluable EGFR expression assay results. Of these, 95% were EGFR-positive. The GC + N arm included 228 patients who were EGFR-positive. In the GC arm, 194 patients were EGFR-positive and did not progress.
While the assessment of efficacy associated with necitumumab maintenance was not planned as a part of SQUIRE, researchers wished to explore this question. Among the patient subgroups noted above, median overall survival from randomization was 16.1 months for GC + N and 14.9 months for GC (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.61-0.95). Median progression-free survival in these GC + N and GC patients was 7.4 months versus 6.9 months, respectively (HR, 0.81; 95% CI, 0.66-1.00).
In the necitumumab continuation phase, adverse events (AEs) were manageable and consistent with expectations. The most common AEs during necitumumab maintenance included rash (26% all grades; 4% grade 3+), hypomagnesemia (15%; 2%), and anemia (13%; 1%).
Researchers concluded that, in patients with EGFR-expressing tumors, the treatment effect consistently favored GC + N plus necitumumab maintenance compared with GC nonprogressors. This finding is similar to what was observed in the ITT population of SQUIRE with no unexpected increases in AE rates. The trial discussant noted that the treat-to-progression paradigm remains unproven, however, given the unplanned nature of this analysis of the SQUIRE data.
Ciuleanu TE, et al. WCLC 2016. Abstract OA 23.02. ID 4283.