On May 26, 2020, the FDA approved a new indication for the combination of the PD-1 inhibitor Opdivo (nivolumab) and the CTLA-4 inhibitor Yervoy (ipilimumab; both from Bristol Myers Squibb) plus 2 cycles only of chemotherapy as the first-line treatment of patients with recurrent or metastatic non–small-cell lung cancer (NSCLC), including patients with squamous or nonsquamous NSCLC, regardless of PD-L1 expression, and no EGFR or ALK genomic aberrations.
The use of Opdivo plus Yervoy may offer a synergistic mechanism of action against cancer by combining 2 types of immune checkpoint inhibitors—a PD-1 inhibitor and a CTLA-4 inhibitor.
This new approval comes on the heels of the May 15, 2020, approval of these 2 immunotherapies for the first-line treatment of patients with metastatic NSCLC whose tumors express PD-L1 ≥1% and have no EGFR or ALK genomic aberrations.
“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.”Expression of the PD-L1 protein on the tumor often affects the tumor response to treatment, and PD-L1 inhibitors are designed to target NSCLC that is associated with high PD-L1 expression.
“Receiving a diagnosis of advanced lung cancer is devastating,” said Andrea Ferris, President and Chief Executive Officer of LUNGevity. “Today’s announcement is 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 FDA approved this new indication for Opdivo plus Yervoy plus limited chemotherapy based on the results of the phase 3 CheckMate-9LA clinical trial. The study included 361 patients with metastatic or recurrent NSCLC, with and without PD-L1 expression, who received either Opdivo plus Yervoy and 2 cycles of platinum-based chemotherapy or 358 patients who received 4 cycles of platinum-based chemotherapy followed by optional pemetrexed maintenance therapy if eligible, for up to 2 years, or until disease progression or unacceptable side effects.
The FDA approval of this new indication was based on the results of the prespecified interim analysis from the CheckMate-9LA study, which showed that the combination of Opdivo plus Yervoy and limited chemotherapy had superior overall survival compared with chemotherapy alone, regardless of whether patients had PD-L1 expression on the tumor or not.
The average overall survival was 14.1 months with the 2 immunotherapies plus limited chemotherapy compared with 10.7 months with chemotherapy alone.
The overall response rate was 38% with Opdivo plus Yervoy and limited chemotherapy versus 25% with chemotherapy alone.
At 12.7 months, the average overall survival was 15.6 months with Opdivo plus Yervoy plus limited chemotherapy versus 10.9 months with chemotherapy alone. Furthermore, at 1 year, 63% of patients who received the combination immunotherapy plus limited chemotherapy versus 47% of those who received chemotherapy alone were still alive.
Opdivo plus Yervoy is associated with immune-mediated side effects. The most common serious adverse events with these immunotherapies plus chemotherapy were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure.
Serious side effects were reported in 57% of the patients who received the immunotherapy combination with limited chemotherapy; 24% of the patients discontinued treatment because of side effects, and 56% of patients had at least 1 treatment withheld because of side effects. In addition, 7 patients died because of side effects.
