As observed in the intention-to-treat analysis of the SQUIRE trial, adding necitumumab to gemcitabine plus cisplatin significantly improved overall survival in patients with epidermal growth factor receptor (EGFR)-expressing advanced squamous non-small cell lung cancer (NSCLC), a subgroup analysis published in Annals of Oncology has shown.1 However, patients with non-EGFR-expressing tumors did not benefit from the addition of necitumumab to chemotherapy.

In the phase 3 SQUIRE trial, researchers enrolled 1093 patients with stage IV squamous NSCLC. Of those, 982 had evaluable immunohistochemistry results, and 95% had tumor samples expressing EGFR protein.

Participants were randomly assigned 1:1 to receive gemcitabine 1250 mg/m² IV on days 1 and 8 and cisplatin 75 mg/m² IV on day 1 with or without necitumumab 800 mg IV on days 1 and 8 for a maximum of 6 3-week cycles. Patients in the chemoimmunotherapy arm who did not experience disease progression continued receiving necitumumab alone until disease progression or unacceptable toxicity.

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Results of the subgroup analyses showed that median overall survival was 11.7 months (95% CI, 10.7-12.9) with necitumumab vs 10.0 months (95% CI, 8.9-11.4) without it among patients with EGFR-expressing tumors (HR, 0.79; 95% CI, 0.69-0.92; P = .002).

In contrast, researchers found that in the 5% of patients with tumors without detectable EGFR protein, there was no survival advantage with necitumumab.

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Of note, patients with non-EGFR-expressing tumors had a higher incidence of grade 3 or higher hypomagnesemia and rash compared with patients with EGFR-expressing advanced squamous NSCLC.

The U.S. Food and Drug Administration approved the EGFR antagonist in 2015 for first-line treatment of patients with metastatic squamous NSCLC, in combination with gemcitabine and cisplatin. Necitumumab is not indicated for non-squamous NSCLC.


  1. Paz-Ares L, Socinski MA, Shahidi J, et al. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small cell lung cancer [published online ahead of print May 20, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw214.