In a new study entitled “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, randomised, controlled phase 3 trial” researchers showed that adding a fully human monoclonal antibody, necitumumab, to a chemotherapy regiment (gemcitabine and cisplatin) significantly improved overall survival in patients with stage IV squamous non-small cell lung cancer, thus representing a new first-line treatment option for this disease. The study was published in the journal Lancet Oncology.
Necitumumab is a fully human monoclonal antibody directed against a specific protein, the epidermal growth factor receptor (EGFR). Cancer cells are characterized by a higher proliferative rate, when compared to normal cells. This is achieved by multiple mechanisms, including mutations that lead to an overexpression of EGFR – in this way, cancer cells are capable of “capturing” more epidermal growth factor that fuels their division and growth.
Therefore, cancer cells coated with EGFR are different from their surrounding healthy cells allowing drugs designed to target EGFR to direct the immune system towards these particular cells. This is what occurs with necitumumab – it binds to EGFR in cancer cells and works as a flag signal for the immune system to attack cancer cells.
In this randomized Phase III clinical trial, known as SQUIRE, researchers enrolled 1,093 patients (from 184 investigative sites in 26 countries) with confirmed stage IV squamous non-small-cell lung cancer and who had not received any previous chemotherapy. They were randomly assigned to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548) (gemcitabine and cisplatin is a a highly effective combination chemotherapy), regardless of EGFR mutation status. The primary endpoint was overall survival. The team observed that adding necitumumab to gemcitabine and cisplatin chemotherapy significantly increased squamous non-small-cell lung cancer patients overall survival: 11.5 months for necitumumab/ gemcitabine and cisplatin versus 9.9 months for gemcitabine and cisplatin alone.
Fred R. Hirsch, MD, PhD, at University of Colorado Cancer Center, CEO of the International Association for the Study of Lung Cancer, and one of the study leading authors noted, “We haven’t seen any new drug approvals in first-line squamous lung cancer in many, many years. I’m very excited to see a new agent that has survival benefit in this space. 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.”