Although the addition of chemotherapy did not prolong OS (HR, 0.88), the combined strategy led to significant benefits compared to the immunotherapy-only approach with respect to PFS (7.7 vs. Patients were allocated to either durvalumab plus tremelimumab followed by durvalumab maintenance (n = 150) or the same regimen plus platinum doublet chemotherapy followed by durvalumab alone or combined with pemetrexed, depending on histology (n = 151). Indeed, approval in the USA has been granted by the Food and Drug Administration in May 2020.Īnother trial to assess the combined first-line approach of dual checkpoint inhibition and chemotherapy in stage IV NSCLC is the international, randomized phase II CCTG BR.34 study. Overall, the CheckMate 9LA study demonstrated that NI plus a limited course of chemotherapy should be considered as a new first-line treatment option for patients with advanced NSCLC. Immune-related AEs were mostly grades 1 and 2. The combination did not induce any new AEs any-grade treatment-related AEs mainly included nausea, anemia, asthenia, and diarrhea. Patients fared better regarding survival with the immunotherapy-based approach regardless of histology (squamous vs. The OS advantage increased over time according to updated results obtained after a follow-up of 12.7 months, median OS was 15.6 vs. OS was defined as the primary endpoint.Īfter a minimum follow-up of 8.1 months, CheckMate 9LA met its primary endpoint at the time of the pre-planned interim OS analysis, with a statistically significant benefit for the immunotherapy-based regimen compared to chemotherapy only (14.1 vs. In the control arm (n = 358), four cycles of chemotherapy were administered, followed by optional pemetrexed maintenance in patients with non-squamous tumors. Among 719 patients with stage-IV or recurrent NSCLC, 361 received NI combined with two cycles of chemotherapy. The phase III, randomized CheckMate 9LA trial was conducted based on the assumption that adding a limited course of chemotherapy to first-line NI might provide rapid disease control while building on the durable OS benefit observed with NI in CheckMate 227. Two cycles of chemotherapy plus checkpoint blockade: CheckMate 9LA In May 2020, the regimen has received approval in the USA in this indication, while the European application was withdrawn four months earlier. The authors concluded that NI is a novel chemotherapy-sparing first-line treatment option for patients with advanced NSCLC. Treatment-related select AEs of NI affecting the skin, gastrointestinal tract, endocrine system and other areas decreased over time. The extended safety follow-up over at least 36.3 months did not reveal any new signals for the combination. Similar results were observed for the group with PD-L1 < 1 % (82 % vs. This showed that among patients with PD-L1 ≥ 1 %, 70 % of those achieving complete or partial responses at six months with NI were alive at three years in the chemotherapy arm, this applied only to 39 %. Also, the combination showed lasting superiority over both nivolumab monotherapy and nivolumab plus chemotherapy independent of PD-L1 expression.Īn exploratory landmark analysis assessed the impact of response at six months on long-term OS. More than one third of all responders remained in response after three years with NI (38 % and 34 % for PD-L1 expressors ≥ 1 % and < 1 %, respectively), while the respective rates in the chemotherapy group ranged below 5 %. 22 % with the combination and chemotherapy, respectively (HR, 0.79). In Part 1a, 3-year OS rates were 33 % vs. Patients in Part 1a showed PD-L1 expression ≥ 1 %, while those in Part 1b tested PD-L1–negative (< 1 %).Īt three years, first-line NI continued to provide long-term benefits compared to chemotherapy regardless of PD-L1 expression. chemotherapy (n = 186) and nivolumab plus chemotherapy (n = 177). Part 1 consisted of Part 1a that compared NI (n = 396) with chemotherapy (n = 397) and nivolumab monotherapy (n = 396), as well as Part 1b which assessed NI (n = 187) vs. presented the updated 3-year efficacy and safety results from Part 1 of the trial. First-line nivolumab plus ipilimumab (NI) was shown to significantly prolong OS compared to chemotherapy in patients with advanced NSCLC irrespective of tumor PD-L1 expression in the randomized, phase III CheckMate 227 study.
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