SQUIRE Analysis Points To EGFR Protein Expression As Necitumumab Biomarker

EGFR protein expression in stage IV squamous non-small-cell lung cancer linked to adjuvant necitumumab benefit

medwireNews: A SQUIRE trial analysis confirms that the addition of necitumumab to gemcitabine and cisplatin improves the survival of patients with stage IV squamous non-small-cell lung cancer (NSCLC) whose tumours express epidermal growth factor receptor (EGFR) protein.

The phase III open-label trial’s initial intention-to-treat findings demonstrated significantly improved overall survival (OS) for patients given necitumumab plus chemotherapy compared with those treated with chemotherapy alone, say Luis Paz-Ares, from University Hospital 12 De Octubre in Madrid, Spain, and co-workers.

The current report, published in the Annals of Oncology, focused on the 982 patients with evaluable immunohistochemistry results, the majority (95%) of whom had tumour samples expressing EGFR protein.

Among those with EGFR protein expression, OS was significantly longer in the 462 patients given necitumumab plus gemcitabine and cisplatin than the 473 given gemcitabine plus cisplatin, at a median of 11.7 months versus 10.0 months and a stratified hazard ratio (HR) of 0.79.

Progression-free survival (PFS) was statistically significantly longer with necitumumab plus chemotherapy than with chemotherapy alone, at 5.7 versus 5.5 months and an HR of 0.84.

And further analysis showed the OS and PFS benefit of necitumumab in patients with tumour EGFR protein expression regardless of age, gender, ethnicity, smoking habit, performance status and geographical region.

By contrast, patients without tumour EGFR protein expression did not show improved OS or PFS with adjuvant necitumumab plus chemotherapy than chemotherapy alone, with nonsignificant HRs of 1.52 and 1.33, respectively.

“SQUIRE results suggest that the small group of patients with no detectable EGFR protein may not benefit from the addition of necitumumab to chemotherapy”, the investigators write. 

However, they caution that the small number of EGFR protein-negative patients in the SQUIRE study and the complexity of the EGFR pathway in NSCLC means the results “are not conclusive regarding the lack of benefit in patients with [no EGFR protein expression]”. 

The results therefore highlight the need for further efforts in understanding the EGFR pathway of the disease, the team emphasizes.


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. Ann Oncol 2016; Advance online publication 20 May. doi: 10.1093/annonc/mdw214

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