medwireNews: CheckMate 9LA findings reported at the virtual 2020 ASCO Annual Meeting support the use of nivolumab plus ipilimumab alongside first-line, histology-driven chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients without sensitizing EGFR or ALK mutations.
The phase 3 open-label trial met its primary endpoint of improved overall survival (OS) at the interim analysis after a minimum of 8.1 months of follow-up in the study participants with stage IV or recurrent NSCLC, Martin Reck (Lung Clinic Grosshansdorf, Germany) told delegates.
Median OS was 14.1 months for the 361 patients randomly assigned to receive nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks, alongside two cycles of chemotherapy, versus 10.7 months for the 358 patients given four cycles of chemotherapy, with an option for pemetrexed maintenance for patients with nonsquamous histology. This gave a significant hazard ratio (HR) for death of 0.69 in favor of the combination arm.
And after a minimum of 12.7 months of follow-up, the OS findings were updated to a median 15.6 months with nivolumab plus ipilimumab and chemotherapy and 10.9 months for chemotherapy alone, with a significant HR of 0.66. The 1-year OS rates were 63% and 47%, respectively.
Subgroup analysis indicated that the combination regimen gave rise to longer median OS than chemotherapy alone for both squamous (14.5 vs 9.1 months, HR=0.62) and nonsquamous histology (17.0 vs 11.9 months, HR=0.69), and for both PD-L1-positive (≥1%, HR=0.64) and PD-L1-negative tumors (<1%, HR=0.62).
Reck highlighted an “interesting signal [for] survival benefit” among patients with central nervous system metastases, for whom the combination regimen appeared to be especially efficacious (HR=0.38 versus 0.37 in those without).
However, the combination with chemotherapy may have lower efficacy than chemotherapy alone in patients older than 75 years and never smokers, he commented.
Progression-free survival was significantly better with nivolumab plus ipilimumab and chemotherapy than chemotherapy alone, at a median 6.7 versus 5.0 months and a HR of 0.68.
And the objective response rate was 38% with the combination versus 25% for chemotherapy alone, with the significant odds ratio of 1.9 reflecting a better disease control rate (84 vs 76%) and a lower rate of primary progression (9 vs 13%) . Duration of response was a median of 11.3 months with the combination versus 5.6 months for chemotherapy alone, with response lasting for at least 12 months in49% versus 24% of patients.
Reporting the safety data, Reck noted that patients given nivolumab plus ipilimumab with chemotherapy had a longer duration of treatment than those given only chemotherapy (median 6.1 versus 2.4 months), and that there were was a “low” fatal toxicity rate of 2% in both arms.
Grade 3–4 treatment-related adverse events (TRAEs) occurred in 47% of patients given nivolumab plus ipilimumab and chemotherapy versus 38% of controls, with 16% and 5% of such events leading to discontinuation of any treatment, respectively. The most common TRAEs at any grade were nausea, anemia, asthenia, and diarrhea, the presenter said.
Reck concluded: “The CheckMate 9LA demonstrated that the combination of nivolumab and ipilimumab, together with a limited course of chemotherapy, should be considered as a new first-line treatment opportunity for patients with non-small-cell lung cancer.”
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2020 ASCO Annual Meeting; 29–31 May