NEW YORK – Bristol Myers Squibb (BMS) yesterday announced that the US Food and Drug Administration (FDA) has approved the combination of the immune checkpoint inhibitor drugs nivolumab (Opdivo) and ipilimumab (Yervoy) together with two cycles of platinum-doublet chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer. The treatment combination was approved for patients without EGFR or ALK gene mutations regardless of their PD-L1 status.
The FDA approval comes in the wake of positive results from the CheckMate 9LA trial, which randomized patients to receive either nivolumab and ipilimumab plus two cycles of platinum-doublet chemotherapy or to receive four cycles of platinum doublet chemotherapy alone. For patients receiving the combination therapy, the median overall survival was 14.1 months compared to 10.7 months for those receiving the chemotherapy alone. In a follow-up analysis performed after 12.7 months, the overall survival benefit was sustained with patients on the immunotherapy combination demonstrating a median overall survival benefit of 15.6 months versus 10.9 months in the chemotherapy arm.
In addition to the overall survival benefit, the nivolumab, ipilimumab, and chemotherapy combination demonstrated progression-free survival and overall response rate benefits compared to chemo alone. The dosing for the approved indication is recommended at 360 mg of nivolumab every 3 weeks with ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy. The nivolumab and ipilimumab portion of the treatment is continued until disease progression, unacceptable toxicity, or up to 2 years without disease progression.
Importantly, the checkpoint inhibitor plus chemo combination did result in significant toxicities during the CheckMate 9LA trial; serious adverse events were reported for 57 percent of patients receiving nivolumab, ipilimumab, and chemo together, and 24 percent of patients had to discontinue treatment due to adverse events. The percentage of patients experiencing grade 3 or 4 adverse events, 47 percent, was not an improvement over chemotherapy alone, which resulted in 38 percent of patients experiencing the same.
The approval follows the FDA's May 15 first-line approval for nivolumab and ipilimumab without chemotherapy for non-small cell lung cancer, a drug combination for which patients needed to have a PD-L1 score of one percent or more. That approval presents a chemotherapy-free first-line option for this patient population, though some oncologists independent of BMS have since raised questions about whether the two checkpoint inhibitors offer any benefit over other single-agent checkpoint inhibitors already approved in this setting, such as pembrolizumab (Merck's Keytruda). BMS has highlighted the duration of survival seen for this approval as well as the potentially synergistic method of action between the PD-1 inhibitor, nivolumab, and the CTLA-4 inhibitor, ipilimumab, as unique benefits of the combination.
The new approval with the addition of limited chemotherapy expands the group of patients eligible to receive the drug combination, since PD-L1 status is not factored into this approval.
"Non-small cell lung cancer is a complex disease that requires multiple treatment options to address the needs of different patient populations," Adam Lenkowsky, BMS' general manager and head of US oncology, immunology, and cardiovascular, said in a statement about recent nivolumab and ipilimumab approvals. "This second approval of an Opdivo plus Yervoy-based combination for the first-line treatment of advanced NSCLC now gives more patients access to a dual immunotherapy approach that can be administered with or without limited chemotherapy, depending on the patient and their PD-L1 status, and the possibility of a chance to live longer."
Results from the CheckMate 9LA trial will be presented as an oral abstract session during the 2020 American Society of Clinical Oncology's annual virtual meeting.