Survival Trends Higher With Necitumumab in EGFR FISH-Positive Squamous NSCLC

Survival for patients with metastatic squamous non–small cell lung cancer whose tumors were positive for EGFR copy number as determined by FISH analysis tended to be better when the EGFR antibody necitumumab was added to their conventional chemotherapy.

Fred R. Hirsch, MD, PhD

Survival for patients with metastatic squamous non—small cell lung cancer (NSCLC) whose tumors were positive for EGFR copy number as determined by FISH analysis tended to be better when the EGFR antibody necitumumab was added to their conventional chemotherapy. More research is needed, however, to see if the potential benefit holds up, according to findings from a biomarker analysis of findings from the phase III SQUIRE trial.

Study author Fred R. Hirsch, professor of Medicine and Pathology at the University of Colorado, presented the results on behalf of his coauthors at a press conference September 9 during the 2015 World Lung Cancer Conference (WCLC) in Denver.

Hirsch noted that while squamous lung cancer represents 25% to 30% of all lung cancers, therapeutic options have been lacking for decades.

The additional analyses Hirsch reported at WCLC were based on tumor samples from the SQUIRE trial published earlier this year in Lancet Oncology.1 In that trial, 1093 patients with stage IV NSCLC and an ECOG performance status of 0-2 were evenly randomized to first-line treatment with gemcitabine (1250 mg/m2 on days 1 and 8) plus cisplatin (75 mg/m2 on day 1), with or without necitumumab (absolute IV dose 800 mg). The treatment cycle was 21 days for a maximum of 6 cycles.

At a follow-up of approximately 2 years, median overall survival (OS) in the necitumumab arm was significantly longer (11.5 months), compared with 9.9 months for patients receiving the gemcitabine-cisplatin regimen only (HR, 0.84; 95% CI, 0.74-0.96; P = .012). The 1-year OS rate was 47.7% versus 42.8%, and the 2-year OS rate was 19.9% compared with 16.5%, for the necitumumab and chemotherapy arms, respectively.

These findings provided the basis for the FDA Oncologic Drugs Advisory Committee’s July 2015 decision to support the approval of necitumumab as a first-line treatment in combination with gemcitabine and cisplatin for patients with advanced squamous NSCLC.

Hirsch and his SQUIRE study colleagues conducted a further analysis of 982 patients with evaluable immunohistochemistry (IHC) assay results. Nearly all of these patients (95.2%) had tumor samples expressing EGFR protein; only 4.8% had tumors without detectable EGFR protein. The investigators’ analysis revealed no consistent trend for the relationship between either OS or progression-free survival (PFS) with EGFR protein based on IHC values when comparing the two treatment arms.

EGFR analyses, based on the FISH assays, were more intriguing. Archived tumor samples with valid FISH results were available for 51% of SQUIRE patients, and of these, 37.3% (n = 208) had increased EGFR copy number. Although median OS trended more favorably for patients with EGFR FISH—positive tumors in the necitumumab arm (12.6 months vs 9.2 months with gemcitabine-cisplatin only), the result was not significant (HR, 0.70; 95% CI, 0.52-0.96).

OS for patients whose FISH assays were negative for EGFR copy number was also better with necitumumab (11.1 vs 10.7 months), but not significantly so (HR, 1.02). PFS was longer, though again, not significantly, among patients with EGFR FISH—positive tumors who were treated with necitumumab (6.1 vs 5.1 months [HR, 0.71; 95% CI, 0.52-0.97]).

Hirsch said that although the findings did not achieve statistical significance, they are important:

“Is it clinically meaningful? I would say, yes.”

“Copy number detected by this particular assay—fluorescent in situ hybridization—seems to predict a better outcome and could in the future be used for effective selection of EGFR antibodies,” he said, adding that the findings demonstrate sufficient potential trends to be investigated in future trials.


  1. Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non—small cell lung cancer (SQUIRE): an open-label, randomized, controlled phase 3 trial. Lancet Oncol. 2015;16(7):763-774.
  2. Boyle T, Thatcher N, Paz-Ares L, et al. EGFR IHC and FISH correlative analyses (SQUIRE trial): necitumumab + gemcitabine-cisplatin vs gemcitabine-cisplatin in 1st-line squamous NSCLC . Presented at: 16th World Conference on Lung Cancer; September 6-9; Denver, CO. Abstract 32:05.


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