The addition of the anti-EGFR antibody necitumumab to gemcitabine-cisplatin chemotherapy resulted in a modest but significant benefit to patients with stage IV squamous cell non-small-cell lung cancer, according to results of the SQUIRE study presented at ASCO.
The addition of the anti-EGFR antibody necitumumab to gemcitabine-cisplatin chemotherapy resulted in a modest but significant benefit to patients with stage IV squamous cell non-small-cell lung cancer (NSCLC), according to results of the SQUIRE study presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
Squamous histology accounts for about 25% to 30% of NSCLC, according to study presenter Nick Thatcher, MB, PhD, of Christie Hospital in Manchester, England. “There has been very limited progress over the last few years, compared to non-squamous cancer, and there are basically no relevant oncogenic drivers that can help us with our treatment, at least at the moment.”
In this trial, 545 patients received necitumumab (Lilly) along with gemcitabine and cisplatin, and 548 received only gemcitabine-cisplatin therapy. If there was no disease progression in the necitumumab group after 6 cycles of therapy, patients continued with necitumumab monotherapy. Most of the patients were male (83% and 84% in the two groups), and more than 90% were smokers.
The primary endpoint of overall survival was significantly better in the necitumumab group, with a median of 11.5 months vs 9.9 months, for a hazard ratio of 0.84 (95% CI, 0.74-0.96; P = .012). The 1-year overall survival (OS) was 47.7% and 42.8% in the two groups, and 2-year OS was 19.9% and 16.5%. Subgroup analyses showed somewhat improved results in younger patients (< 70 years).
The progression-free survival difference was very small, at 5.7 months with necitumumab and 5.5 months without it, but this did reach significance with an HR of 0.85 (95% CI, 0.74-0.98; P = .020). There was a slight, non-significant increase in the objective response rate, at 31.2% vs 28.8% (P = .400). Of the necitumumab patients, 275 (51%) did go on to receive the study drug as monotherapy, with a median of 4 cycles.
Notably, the study found that EGFR expression as measured by H-score was not predictive of outcome. Julie R. Brahmer, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, was the discussant for the session and said the lack of biomarker efficacy was the most disappointing aspect of this trial. “The biomarker did not work, so we’re back at square one without a biomarker for this antibody,” she said. “I think at this point let’s put the H-score to rest.”
Overall the adverse events (AEs) were similar between the two groups, though the combination group did have more grade 3 or greater AEs. There was more grade 3/4 hypomagnesemia (9.3% vs 1.1%), skin rash (7.1% vs 0.4%), and venous thromboembolic events (5% vs 2.6%). Treatment-related death occurred in 2.8% of necitumumab patients and 1.8% of chemotherapy-alone patients.
“I think it’s important to remember we’re dealing with squamous cell lung cancer,” Thatcher said. “The SQUIRE results are important in the search for a new treatment for patients with metastatic squamous cell lung cancer. It’s the first time that we’ve seen benefit in this group of patients over the last 20 or 25 years.”