Adding necitumumab (IMC-11F8) to gemcitabine (Gemzar) and cisplatin chemotherapy may improve overall survival (OS) in patients with advanced squamous non-small cell lung cancer, according to new phase III clinical trial results published in Lancet Oncology.
Adding necitumumab (IMC-11F8) to gemcitabine (Gemzar) and cisplatin chemotherapy may improve overall survival (OS) in patients with advanced squamous non-small cell lung cancer, according to new phase III clinical trial results published in Lancet Oncology.1
Necitumumab is a recombinant IgG1 human monoclonal antibody designed to bind and block the ligand binding site of EGFR.
The investigators report that necitumumab may represent a new first-line treatment option for patients with non-small cell lung cancer (NSCLC). Regulatory submission of necitumumab for US Food and Drug Administration (FDA)-approval has already been completed and a decision is expected soon.
Researchers conducted an open-label, randomized phase III study at 184 investigative sites in 26 countries. The study examined 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). The researchers found that the addition of necitumumab resulted in a median OS of 11.5 months compared to a median OS of 9.9 months with the two chemotherapies alone.
Study investigator Fred Hirsch, MD, PhD, who is with the University of Colorado Cancer Center in Denver, said the findings are very good news because there has not been a new drug approval in first-line squamous lung cancer in many, many years. Dr. Hirsch, who is also CEO of the International Association for the Study of Lung Cancer, said although there were more side effects in the group treated with necitumumab in combination with the two chemotherapies, the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations.2
Patients were eligible for the study regardless of EGFR mutation status. The investigators performed biomarker analysis of tissue samples and evaluated patient tumor samples for amplification of the EGFR gene. The efficacy of the drug in specific patients with EGFR amplification will be released during the 16th World Conference on Lung Cancer, September 6-9, 2015 in Denver.
Necitumumab was given to the patients between Jan 7, 2010 and Feb 22, 2012. In the trial, 545 patients received necitumumab plus gemcitabine and cisplatin, and 548 patients received gemcitabine and cisplatin. Chemotherapy consisted of gemcitabine 1250 mg/m2, administered intravenously over 30 minutes on days 1 and 8 of a 3-week cycle. Cisplatin 75 mg/m2, was administered intravenously over 120 minutes on day 1 of a 3-week cycle. In the necitumumab arm, patients were administered 800 mg intravenously over a minimum of 50 minutes on days 1 and 8. Necitumumab was continued after chemotherapy was completed, until disease progression, or intolerable toxic side effects occurred.
The number of patients with at least one grade 3 or worse adverse event was 72% higher in the necitumumab arm (388 of 538 patients) than in the gemcitabine group. It was 62% higher (333 of 541) than cisplatin group. The incidences of serious adverse events were also higher in the necitumumab arm, and more patients had grade 3/4 hypomagnesaemia (47 of 538 patients in the necitumumab group compared to 6 of 541 in the gemcitabine and cisplatin group).
“This is an improvement. Based on this large prospective study in first-line therapy of squamous lung cancer, a subtype of lung cancer where there is an urgent unmet need for treatment improvement, the drug warrants approval,” says Hirsch.