Reck noted that an increase in median OS was observed with nivolumab/ipilimumab versus chemotherapy across patient subgroups, including those with bone metastases (11.9 vs 8.3 months, respectively HR, 0.73), CNS metastases (19.9 vs 7.9 months HR, 0.47), and current/former smokers (16.2 vs 10.4 HR, 0.68). Patients with an ongoing response at 12 months comprised 52% of the immunotherapy group and 24% of the chemotherapy group those rates at 24 months were 34% and 12%, respectively. In the chemotherapy group, the response rate was 24.5% with a DOR of 5.6 months. The ORR in the nivolumab/ipilimumab group was 38.0% with a median duration of response (DOR) of 13.0 months. Corresponding rates at 24 months were 19% and 8%. At 12 months, the rate of PFS in the immunotherapy group was 33% versus 20% with chemotherapy.
Median PFS continued to favor treatment with nivolumab plus ipilimumab compared with chemotherapy, at 6.7 versus 5.3 months, respectively (HR, 0.67 95% CI, 0.56-0.79). Rates of OS at 12- and 24-month time points were also greater for the PD-1/CTLA-4 combination, at 63% and 38%, respectively, compared with 47% and 26% with chemotherapy alone. With a minimum of 2-years of follow-up, the median OS in the experimental therapy arm was 15.8 months versus 11.0 months with chemotherapy alone (HR, 0.72 95% CI, 0.61-0.86). In the control group, 47% of patients with a PFS event (n = 334) received subsequent systemic therapy, 37% went on to immunotherapy, 24% had any additional chemotherapy, and 4% received platinum-doublet chemotherapy.
In the group receiving the experimental regimen, 40% of patients with PFS events (n = 307) went on to receive additional systemic therapy, 8% had subsequent immunotherapy, 37% had chemotherapy, and 22% received platinum-doublet chemotherapy. In the immunotherapy and chemotherapy-alone arms, 358 and 349 patients, respectively, received active treatment. Stratification was performed by PD-L1 expression level (<1% or ≥1%), sex, and histology (squamous or nonsquamous).
The primary end point of the trial was overall survival (OS), with secondary and exploratory outcome measures of progression-free survival (PFS), objective response rate (ORR), efficacy by PD-L1 expression level, and safety. Patients in the chemotherapy arm with nonsquamous histology had the option to continue with pemetrexed maintenance. Patients were randomized in a 1:1 fashion to either 2 cycles of chemotherapy every 3 weeks with the addition of nivolumab at 360 mg every 3 weeks and ipilimumab at 1 mg/kg every 6 weeks or 3 cycles of chemotherapy. Patients included on the trial were those with stage IV NSCLC without prior systemic therapy for their disease and an ECOG performance status of 0 or 1 (n = 719).
These data indicate a benefit of the combination across key patient subgroups characterized by PD-L1 expression, histology, and the presence of central nervous system metastases.
1ĭata from this trial, which initially led to the approval of the combination in patients with either frontline metastatic or recurrent NSCLC who did not harbor EGFR or ALK tumor mutations, 2 were presented by Martin Reck, MD, PhD, of Hospital Grosshansdorf in Germany. Updated efficacy data from the phase CheckMate 9LA trial (NCT03215706) of nivolumab (Opdivo) and ipilimumab (Yervoy) plus 2 cycles of platinum-based chemotherapy continued to show efficacy versus chemotherapy alone for patients with advanced non–small cell lung cancer (NSCLC), according to a 2-year follow-up analysis presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.