The subgroup of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced squamous non-small cell lung cancer (NSCLC) benefitted from the addition of necitumumab to gemcitabine plus cisplatin, a late-breaking study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1

The phase 3 SQUIRE trial demonstrated that adding necitumumab to gemcitabine-cisplatin chemotherapy improved overall survival by 1.6 months in patients with stage 4 squamous NSCLC as compared with chemotherapy alone. Researchers sought to conduct a subgroup analysis of the SQUIRE trial to investigate whether those with EGFR-expressing tumors have improved outcomes vs those without EGFR mutations.

Patients were randomly assigned 1:1 to receive gemcitabine 1250 mg/m2 intravenously (IV) on days 1 and 8 plus cisplatin 75 mg/m2 IV on day 1 with or without necitumumab 800 mg IV on days 1 and 8, every 21 days for a maximum of 6 cycles. Patients receiving chemoimmunotherapy who did not experience progression could receive necitumumab alone until disease progression or unacceptable toxicity. Of the 982 patients who participated in SQUIRE, 95% had EGFR-expressing tumors and 5% did not.

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Results showed that in this subpopulation, adding necitumumab to chemotherapy improved overall survival by 21% (HR, 0.79; 95% CI, 0.69 – 0.92; P = .002) and progression-free survival by 16% (HR, 0.84; 95% CI, 0.72 – 0.97; P = .018). Patients with no EGFR in their tumors experienced no benefit from the addition of necitumumab.

“Necitumumab is targeted at EGFR so it makes sense that the drug is active in patients with the receptor,” said lead author Luis Paz-Ares, MD, chief of medical oncology at the University Hospital 12 De Octubre in Madrid, Spain. “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.”

Dr Paz-Ares noted that a confirmatory study in patients with EGFR-negative tumors is necessary to evaluate whether they are appropriate candidates for necitumumab or not.

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Necitumumab is an EGFR antagonist approved by the U.S. Food and Drug Administration for the first-line treatment of patients with metastatic squamous NSCLC in combination with gemcitabine and cisplatin.


  1. Paz-Ares L, Socinski MA, Shahidi J, et al. Subgroup analyses of patients with epidermal growth factor receptor (EGFR)-expressing tumors in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) plus necitumumab (N) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.