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.
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.
RELATED: Navigating the 2016 ASCO Annual Meeting: Immunotherapy, Precision Medicine ‘Significant Themes’
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.
- 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.