Necitumumab benefit greatest in patients with EGFR–expressing NSCLC

Patients with epidermal growth factor receptor-expressing stage IV squamous non–small cell lung cancer demonstrated the greatest OS and PFS benefits with the addition of necitumumab to chemotherapy, according to a subgroup analysis of the SQUIRE trial presented at the European Lung Cancer Conference.

“This subgroup analysis shows that the effect of necitumumab [Portrazza, Eli Lilly] was slightly greater in patients with EGFR–expressing tumors than it was in the entire SQUIRE population," Robert Pirker, MD, professor and program director for lung cancer at Vienna General Hospital in Austria, who was not involved with the study, said in a press release. “It indicates that immunohistochemical detection of [EGFR] improves clinical activity of necitumumab. The findings are consistent with previous studies suggesting that monoclonal antibodies in combination with chemotherapy work better in patients with EGFR–expressing cells.”

Overall results of SQUIRE demonstrated the addition of necitumumab to the standard of care, gemcitabine and cisplatin, improved OS and PFS for patients with stage IV squamous NSCLC.

Luis Paz-Ares, MD, chief of medical oncology at University Hospital 12 de Octubre in Madrid, Spain, and colleagues conducted a subgroup analysis to investigate any association between necitumumab benefit and EGFR protein expression.

Of the 982 patients in the trial, 935 (95.2%) had tumor samples with EGFR expression, and 47 patients (4.8%) did not.

Patients with EGFR expression who received necitumumab plus gemcitabine and cisplatin demonstrated improved OS (HR = 0.79; 95% CI, 0.62-0.92) and PFS (HR = 0.82; 95% CI, 0.72-0.97) compared with EGFR–positive patients who received gemcitabine and cisplatin alone.

The benefit associated with the addition of necitumumab to standard of care did not persist in EGFR–negative patients for OS (HR = 1.52; 95% CI, 0.74-3.12) or PFS (HR = 1.33; 95% CI, 0.65-2.7).

“Necitumumab is targeted at EGFR so it makes sense that the drug is active in patients with the receptor,” Paz-Ares said in the press release. “Our analysis showed that the drug had no effect when the receptor was absent, presumably because there was no target to bind to. We cannot make robust conclusions because the subgroup of patients with negative EGFR was very small, but the hypothesis generated here is that those tumors do not respond well to necitumumab.”

Among EGFR–positive patients, those who received necitumumab demonstrated a higher rate of grade 3 or worse hypomagnesemia (9.6% vs. 0.9%) and skin rash (6.4% vs. 0.4%).

Although the European Medicines Agency limited the approval of necitumumab for squamous NSCLC in patients with EGFR expression, because the trial accepted all-comers, the FDA approved necitumumab regardless of EGFR expression because the subgroup analysis was deemed insufficient to conclude EGFR–negative patients are not candidates, Paz-Ares said. – by Nick Andrews

Reference:

Paz-Ares L, et al. Abstract 132O_PR. Presented at: European Lung Cancer Conference; April 13-16, 2016; Geneva.

Disclosure: Paz-Ares reports honoraria from Eli Lilly and Company. Other researchers report advisory board and employee roles with, honoraria from and equity ownership in Eli Lilly and Company.