307 Atezolizumab plus vemurafenib and cobimetinib provides favorable survival outcomes in patients with high tumor mutation burden and proinflammatory gene signature in the phase 3 IMspire150 study
| Autor: | Judit Oláh, Grant A. McArthur, Kalpit Shah, Caroline Robert, Karl D. Lewis, Luis De La Cruz Marino, Paola Queirolo, Paolo A. Ascierto, Christian Hertig, Jacek Mackiewicz, Harper Forbes, Gabriella Liszkay, Ralf Gutzmer, Rodrigo Ramella Munhoz, Yibing Yan |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cobimetinib medicine.medical_specialty business.industry medicine.medical_treatment Hazard ratio Immunotherapy Gene signature lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Placebo lcsh:RC254-282 chemistry.chemical_compound chemistry Atezolizumab Response Evaluation Criteria in Solid Tumors Internal medicine medicine business Vemurafenib medicine.drug |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 8, Iss Suppl 3 (2020) |
| Popis: | Background The phase 3 IMspire150 study (NCT02908672) showed that first-line atezolizumab (A) combined with vemurafenib (V) + cobimetinib (C) improved progression-free survival (PFS) vs placebo (P) + V + C in patients with BRAFV600 mutation–positive advanced melanoma (15.1 vs 10.6 months; hazard ratio [HR] 0.78; 95% CI 0.63–0.97; P=0.0249). Insights into the clinical benefit of the A+V+C triple combination in prognostic molecular subgroups of patients can inform treatment selection and future clinical research. Methods 514 patients were randomized 1:1 to A+V+C (n=256) or P+V+C (n=258). The efficacy endpoints analyzed included PFS and duration of response (DOR) estimated using the Kaplan-Meier method. Outcomes were based on investigator-assessed best overall response per Response Evaluation Criteria in Solid Tumors v1.1. Patients were primarily categorized into binary subgroups defined by tumor mutation burden (TMB; low or high: Results Patients treated with P+V+C with high and low TMB had similar PFS outcomes. However, the magnitude of the PFS benefit with A+V+C vs P+V+C was markedly higher in patients with high TMB (≥10 mutations/Mb) compared with patients with low TMB ( Conclusions There was a trend of larger magnitude of PFS benefit with A+V+C vs P+V+C in PD-L1– patient subgroups, who benefit less with single-agent immunotherapy. The PFS and DOR benefits were more evident in patients with high IFN-gamma or TMB >10 mutations/Mb. Additional multivariate analyses are ongoing to delineate the PFS trends observed. Trial Registration ClinicalTrials. gov, identifier NCT02908672 |
| Databáze: | OpenAIRE |
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