Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2026
Early Detriment Analysis of First-Line Nivolumab plus Ipilimumab-Based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo identify variables associated with early detriment on first-line dual immunotherapy from the phase III CheckMate 227 and CheckMate 9LA studies. PATIENTS AND
methodsAdults with stage IV/recurrent non-small cell lung cancer (NSCLC) lacking EGFR/ALK alterations were randomized to nivolumab plus ipilimumab, nivolumab (PD-L1 ≥1%) or nivolumab plus chemotherapy (PD-L1 <1%), or chemotherapy in CheckMate 227 or to nivolumab plus ipilimumab with chemotherapy or chemotherapy in CheckMate 9LA. Multivariable analyses were used to identify factors associated with rapid progression (progression or death within 3 months of randomization) from nivolumab plus ipilimumab in CheckMate 227, and univariate analyses were used to assess rapid progression from nivolumab plus ipilimumab with/without the addition of chemotherapy from CheckMate 227 and CheckMate 9LA.
resultsRapid progression rates were 40% with nivolumab plus ipilimumab versus 26% with chemotherapy. High neutrophil-to-leukocyte ratio, baseline tumor mutational burden (TMB) <14 mutations per megabase, tumor PD-L1 <1%, low albumin level, and higher-than-median baseline monocytic myeloid-derived suppressor cell (M-MDSC) level were associated with rapid progression in patients treated with nivolumab plus ipilimumab. Early detriment was not observed with nivolumab plus ipilimumab with chemotherapy across subgroups from CheckMate 9LA. Long-term survival favored nivolumab plus ipilimumab-containing treatment across subgroups.
conclusionsNeutrophil-to-leukocyte ratio, TMB, tumor PD-L1 expression, albumin level, and baseline M-MDSC level were associated with rapid progression in patients with metastatic NSCLC treated with first-line nivolumab plus ipilimumab. Relative to chemotherapy, early detriment was observed with nivolumab plus ipilimumab across biomarker subgroups but not with nivolumab plus ipilimumab with chemotherapy. Long-term benefit was maintained with both regimens.
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