Mark A Socinski1, Mustafa Özgüroğlu2, Augusto Villegas3, Davey Daniel4, David Vicente5, Shuji Murakami6, Rina Hui7, Jhanelle E Gray8, Keunchil Park9, Mark Vincent10, Helen Mann11, Michael Newton12, Phillip A Dennis12, Scott J Antonia8. 1. AdventHealth Cancer Institute, Orlando, FL. Electronic address: Mark.Socinski.MD@AdventHealth.com. 2. Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey. 3. Cancer Specialists of North Florida, Jacksonville, FL. 4. Sarah Cannon Research Institute/Tennessee Oncology, Chattanooga, TN. 5. Hospital Universitario Virgen Macarena, Seville, Spain. 6. Kanagawa Cancer Center, Yokohama, Japan. 7. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia. 8. Moffitt Cancer Center, Tampa, FL. 9. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 10. London Health Sciences Centre, London, ON, Canada. 11. AstraZeneca, Cambridge, UK. 12. AstraZeneca, Gaithersburg, MD.
Abstract
BACKGROUND: The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age. PATIENTS AND METHODS: Patients were randomized 2:1 (1-42 days post-CRT) to receive 12-months' durvalumab (10 mg/kg intravenously every-2-weeks) or placebo. We analyzed PFS and OS (unstratified Cox-proportional-hazards models), safety and patient-reported outcomes (PROs: symptoms, functioning, and global-health-status/quality-of-life) in subgroups defined by a post-hoc 70-year age threshold. Data cut-off for PFS was February 13, 2017 and for OS, safety and PROs was March 22, 2018. RESULTS: Overall, 158 of 713 (22.2%) and 555 of 713 (77.8%) randomized patients were aged ≥70 and <70 years, respectively. Durvalumab improved PFS and OS among patients aged ≥70 (PFS: hazard ratio [HR], 0.62 [95% CI, 0.41-0.95]; OS: HR, 0.78 [95% CI, 0.50-1.22]) and <70 (PFS: HR, 0.53 [95% CI, 0.42-0.67]; OS: HR, 0.66 [95% CI, 0.51-0.87]), although the estimated HR-95% CI for OS crossed one among patients aged ≥70. Durvalumab exhibited a manageable safety profile and did not detrimentally affect PROs vs. placebo, regardless of age; grade 3/4 (41.6% vs. 25.5%) and serious adverse events (42.6% vs. 25.5%) were more common with durvalumab vs. placebo among patients aged ≥70. CONCLUSION: Durvalumab was associated with treatment benefit, manageable safety, and no detrimental impact on PROs, irrespective of age, suggesting that elderly patients with unresectable, stage III NSCLC benefit from treatment with consolidation durvalumab after CRT. However, small subgroup sizes and imbalances in baseline factors prevent robust conclusions.
BACKGROUND: The PACIFIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS (the primary endpoints) vs. placebo in patients with unresectable, stage III NSCLC whose disease had not progressed after platinum-based, concurrent chemoradiotherapy (CRT). We report exploratory analyses of outcomes from PACIFIC by age. PATIENTS AND METHODS: Patients were randomized 2:1 (1-42 days post-CRT) to receive 12-months' durvalumab (10 mg/kg intravenously every-2-weeks) or placebo. We analyzed PFS and OS (unstratified Cox-proportional-hazards models), safety and patient-reported outcomes (PROs: symptoms, functioning, and global-health-status/quality-of-life) in subgroups defined by a post-hoc 70-year age threshold. Data cut-off for PFS was February 13, 2017 and for OS, safety and PROs was March 22, 2018. RESULTS: Overall, 158 of 713 (22.2%) and 555 of 713 (77.8%) randomized patients were aged ≥70 and <70 years, respectively. Durvalumab improved PFS and OS among patients aged ≥70 (PFS: hazard ratio [HR], 0.62 [95% CI, 0.41-0.95]; OS: HR, 0.78 [95% CI, 0.50-1.22]) and <70 (PFS: HR, 0.53 [95% CI, 0.42-0.67]; OS: HR, 0.66 [95% CI, 0.51-0.87]), although the estimated HR-95% CI for OS crossed one among patients aged ≥70. Durvalumab exhibited a manageable safety profile and did not detrimentally affect PROs vs. placebo, regardless of age; grade 3/4 (41.6% vs. 25.5%) and serious adverse events (42.6% vs. 25.5%) were more common with durvalumab vs. placebo among patients aged ≥70. CONCLUSION: Durvalumab was associated with treatment benefit, manageable safety, and no detrimental impact on PROs, irrespective of age, suggesting that elderly patients with unresectable, stage III NSCLC benefit from treatment with consolidation durvalumab after CRT. However, small subgroup sizes and imbalances in baseline factors prevent robust conclusions.
Authors: Sally C M Lau; Malcolm Ryan; Jessica Weiss; Aline Fusco Fares; Miguel Garcia; Sabine Schmid; Shelley Kuang; Deirdre Kelly; Ming Sound Tsao; Penelope A Bradbury; Byoung Chun J Cho; Alexander Sun; Srinivas Raman; Andrew Hope; Meredith Giuliani; Benjamin H Lok; Andrea Bezjak; Geoffrey Liu; Natasha B Leighl; Frances A Shepherd; Adrian G Sacher Journal: JTO Clin Res Rep Date: 2021-11-02
Authors: Matthew D Pichert; Maureen E Canavan; Richard C Maduka; Andrew X Li; Theresa Ermer; Peter L Zhan; Michael Kaminski; Brooks V Udelsman; Justin D Blasberg; Henry S Park; Sarah B Goldberg; Daniel J Boffa Journal: JAMA Netw Open Date: 2022-08-01