First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes

Background: In CheckMate 9LA (NCT03215706), first-line nivolumab plus ipili-mumab with chemotherapy (2 cycles) significantly improved overall survival versus chemo-therapy (4 cycles) in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor/anaplastic lymphoma kinase alterations. We present exploratory patient-reported outcomes (PROs; minimum follow-up, 2 years).Methods: In patients (N Z 719) randomised 1:1 to nivolumab plus ipilimumab with chemo-therapy or chemotherapy alone, disease-related symptom burden and health-related quality of life were assessed using the Lung Cancer Symptom Scale (LCSS) and 3-level EQ-5D (EQ-5D-3L). Treatment-phase changes in LCSS average symptom burden index (ASBI), LCSS three-item global index (3-IGI) and EQ-5D-3L visual analogue scale (VAS) and utility index (UI) over time were analysed descriptively and using mixed-effect model repeated mea-sures. Time-to-deterioration/improvement analyses were conducted.Results: Treatment-phase PRO questionnaire completion rates were >80%. Mean treatment-phase changes showed no deterioration from baseline in both arms for LCSS ASBI/3-IGI and EQ-5D-3L VAS/UI; however, minimally important differences were not met. Mixed-effect model repeated measures analyses showed overall reduction in symptom burden from baseline for both arms; changes from baseline for LCSS 3-IGI and EQ-5D-3L VAS/UI were numerically improved with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, but minimally important differences were not met. Nivolumab plus ipilimumab with chemotherapy delayed time-to-definitive-deterioration versus chemo-therapy (LCSS ASBI: hazard ratio, 0.62 [95% confidence interval, 0.45-0.87]); results were similar across PRO measures.Conclusions: At 2-year minimum follow-up, first-line nivolumab plus ipilimumab with chemotherapy reduced the risk of definitive deterioration in disease-related symptom burden and health-related quality of life versus chemotherapy and maintained QoL in pa-tients with metastatic non-small cell lung cancer.Clinical trial registration: ClinicalTrials.gov Identifier, NCT03215706.2023 Published by Elsevier Ltd.

Automated summary

In the CheckMate 9LA study, first-line nivolumab plus ipilimumab with chemotherapy significantly improved overall survival compared to chemotherapy alone in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor/anaplastic lymphoma kinase alterations. We presented exploratory patient-reported outcomes (PROs) with a minimum follow-up of 2 years.