This followed the approval of nivolumab plus ipilimumab for the first-line treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors express PD-L1 ≥1% and have no EGFR or ALK genomic aberrations. The new approval was the sixth indication for the combination of nivolumab plus ipilimumab across 5 types of cancer.
“We have come a long way in understanding the role of dual immunotherapy-based approaches in cancer and the potential impact on patients’ long-term outcomes,” said David P. Carbone, MD, PhD, study investigator and Director of the James Thoracic Oncology Center, Ohio State University. “The positive findings from CheckMate-9LA demonstrate the benefit of combining dual immunotherapy with limited chemotherapy for NSCLC patients regardless of PD-L1 status.”
“Receiving a diagnosis of advanced lung cancer is devastating,” said Andrea Ferris, President and Chief Executive Officer of LUNGevity. She added that the announcement was “welcome news as it provides a new dual immunotherapy-based option for previously untreated patients searching for a treatment that may help extend their lives.”
The approval of the new indication for nivolumab plus ipilimumab and limited chemotherapy was based on the results of the randomized, open-label, multicenter CheckMate-9LA phase 3 clinical trial, which included patients with metastatic or recurrent NSCLC regardless of PD-L1 expression. For the study, patients received either nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy (N = 361) or 4 cycles of platinum-doublet chemotherapy followed by optional pemetrexed maintenance therapy if eligible (N = 358), for up to 2 years, or until disease progression or unacceptable toxicity.
Overall survival (OS) was the primary end point of the study. Secondary efficacy outcomes included progression-free survival, overall response rate (ORR), and duration of response, as determined by blinded independent central review.
The results of the prespecified interim analysis from the CheckMate-9LA study showed that nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy had superior OS versus chemotherapy alone (P = .0006), regardless of PD-L1 expression or tumor histology. The median OS was 14.1 months (95% confidence interval [CI], 13.2-16.2) versus 10.7 months (95% CI, 9.5-12.5), respectively.
Patients treated with nivolumab plus ipilimumab and limited chemotherapy had an ORR of 38% (95% CI, 33-43), compared with an ORR of 25% (95% CI, 21-30) in patients who received chemotherapy alone. After a minimum of 12.7 months of follow-up, the median OS was 15.6 months (95% CI, 13.9-20.0) in the nivolumab plus ipilimumab and limited chemotherapy group, compared with 10.9 months (95% CI, 9.5-12.5) in the chemotherapy-alone group. At 1 year, 63% of patients who received the combination therapy plus limited chemotherapy were still alive, compared with 47% of those who received chemotherapy alone.
As with all other immunotherapies, nivolumab and ipilimumab are associated with immune-mediated adverse events. In the CheckMate-9LA study, the most common (>2%) serious adverse events in patients who received nivolumab and ipilimumab in combination with platinum-doublet chemotherapy were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure.
More than half (57%) of the patients who received the immunotherapy combination with limited chemotherapy reported serious adverse reactions; 24% of patients discontinued treatment because of adverse events, and 56% of patients had at least 1 treatment withheld because of side effects. Fatal adverse reactions occurred in 7 (2%) patients.
