CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC |
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| Institution: | 1. Canadian Cancer Trials Group, Kingston, Ontario, Canada;2. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada;3. The Ottawa Hospital Cancer Centre and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;4. Australasian Lung Cancer Trials Group, Milton, Australia;5. Prince Charles Hospital, University of Queensland, Brisbane, Australia;6. National Health and Medical Research Council (NHMRC) Clinical Trials Centre, Sydney, Australia;7. Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada;8. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval, Québec, Canada;9. Windsor Regional Hospital, Windsor, Ontario, Canada;10. Centre hospitalier de l''Université de Montréal, Montréal, Québec, Canada;11. Cross Cancer Institute, Edmonton, Alberta, Canada;12. Kingston General Hospital, Kingston, Ontario, Canada;13. Humber River Hospital, Toronto, Ontario, Canada;14. Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada;15. Albury Wodonga Regional Cancer Centre, Albury, Australia;p. BC Cancer, Surrey, British Columbia, Canada |
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| Abstract: | IntroductionFirst-line therapy for patients with metastatic NSCLC includes checkpoint inhibitor monotherapy, dual checkpoint inhibition, or combination with chemotherapy. We compared outcomes with combination chemoimmunotherapy versus dual checkpoint inhibition as first-line treatment for patients with metastatic NSCLC.MethodsThis open-label, randomized clinical trial was conducted at 44 sites in Canada and Australia. Patients with treatment-naive, metastatic NSCLC without sensitizing EGFR or ALK alterations were randomized (1:1) to receive treatment with durvalumab plus tremelimumab with or without platinum-doublet chemotherapy. The primary end point was overall survival (OS). Secondary end points were progression-free survival, overall response rate, and safety.ResultsA total of 301 patients were randomized. Median OS was 16.6 months (95% confidence interval CI]: 12.6–19.1) with chemotherapy plus immunotherapy and 14.1 months (95% CI: 10.6–18.3) with immunotherapy (hazard ratio = 0.88, 90% CI: 0.67–1.16, p = 0.46). Median progression-free survival with chemotherapy plus immunotherapy was 7.7 months (95% CI: 5.5–8.5) and 3.2 months (95% CI: 2.7–5.1) with immunotherapy (hazard ratio = 0.67, 95% CI: 0.52–0.88). The overall response rate with chemoimmunotherapy was 42.4% and 29.3% with immunotherapy (adjusted OR = 1.69, 95% CI: 1.04–2.76). The percentage of patients with grade 3 or higher adverse events was 82% in the chemotherapy plus immunotherapy group and 70% in the immunotherapy group. Exploratory analyses of programmed death-ligand 1 expression and blood-based tumor mutation burden revealed no differential treatment effect on OS.ConclusionsThe addition of chemotherapy to durvalumab plus tremelimumab in the first-line treatment of stage IV NSCLC did not improve survival compared with durvalumab plus tremelimumab alone. Further study is warranted to identify patients that benefit from initial immunotherapy alone versus combination chemotherapy plus immunotherapy as first-line treatment. |
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| Keywords: | Immunotherapy Randomized Advanced NSCLC Durvalumab Tremelimumab Chemoimmunotherapy |
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