ELCC 2016: Patients With EGFR-Expressing Non–Small Cell Lung Cancer Benefit Most From Necitumumab Added to Chemotherapy
Patients with epidermal growth factor receptor (EGFR)-expressing advanced squamous non–small cell lung cancer benefit most from necitumumab (Portrazza) added to gemcitabine and cisplatin chemotherapy, according to a subgroup analysis from the SQUIRE trial presented by Paz-Ares et al (Abstract 132O_PR) on April 15 at the European Lung Cancer Conference (ELCC) 2016 in Geneva.
Study Findings
The randomized phase III SQUIRE trial demonstrated that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improved overall survival in patients with stage IV squamous non–small cell lung cancer by 1.6 months compared to chemotherapy alone. The current study analyzed outcomes in the subgroup of patients with EGFR-expressing tumors compared to those with no EGFR.
Out of 982 patients in the SQUIRE trial, 95% had EGFR-expressing tumors and 5% had tumors with no EGFR protein. The addition of necitumumab to gemcitabine and cisplatin chemotherapy improved overall survival and progression-free survival by 21% and 16%, respectively, compared to chemotherapy alone in patients whose tumors expressed EGFR protein. There was no benefit in patients with no EGFR in their tumors.
Lead author Luis Paz-Ares, MD, PhD, Chief of Medical Oncology at the University Hospital 12 De Octubre in Madrid, said, “Necitumumab is targeted at EGFR, so it makes sense that the drug is active in patients with the receptor. 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 EGFR-negative tumors] was very small, but the hypothesis generated here is that those tumors do not respond well to necitumumab.”
Commenting on the Results
“Based on this analysis, the European Medicines Agency has decided that necitumumab is approved only for patients with EGFR-expressing tumors,” continued Dr. Paz-Ares. “On the other hand, the U.S. Food and Drug Administration has taken the more conservative approach, which recognizes that SQUIRE was designed for all comers without prior selection, and this subgroup analysis is insufficient evidence to conclude that patients with EGFR-negative tumors are not candidates.”
He concluded, “Our results need to be interpreted with caution. A confirmatory study in patients with EGFR-negative tumors is needed to assess whether they are good candidates for necitumumab or not.”
Commenting on the findings, Robert Pirker, MD, Program Director for Lung Cancer at the Vienna General Hospital in Vienna, not involved in the study, said, “This subgroup analysis shows that the effect of necitumumab was slightly greater in patients with EGFR-expressing tumors than it was in the entire SQUIRE population. It indicates that immunohistochemical detection of the EGFR receptor improves clinical activity of necitumumab. The findings are consistent with previous studies suggesting that monoclonal antibodies in combination with chemotherapy work better in patients with EGFR-expressing cells.”
Dr. Pirker added that a more thorough analysis is needed. He said, “Information on outcome of patients with cutoff levels higher than in the current analysis would be of interest. We also need to know the effect of necitumumab according to both percentages of positive cells and their staining intensity. This could be combined with fluorescence in situ hybridization analysis to detect gene amplification. This could give us a clearer picture of which patients benefit most from necitumumab.”
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