Abstract
Introduction: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. Methods: Patients were randomized 2:1 (1–42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60–66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. Results: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34–0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35–0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51–1.20]); carboplatin (0.86 [0.60–1.23]); vinorelbine (0.79 [0.49–1.27]); and taxane-based CT (0.73 [0.51–1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62–1.06]). Safety was broadly similar across the CRT subgroups. Conclusion: Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
Original language | English |
---|---|
Pages (from-to) | 30-38 |
Number of pages | 9 |
Journal | Lung Cancer |
Volume | 151 |
Early online date | 26 Nov 2020 |
DOIs | |
Publication status | Published - 1 Jan 2021 |
Keywords
- Chemoradiotherapy
- Chemotherapy
- Immunotherapy
- Non-small-cell lung cancer
- Radiotherapy
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In: Lung Cancer, Vol. 151, 01.01.2021, p. 30-38.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Impact of prior chemoradiotherapy-related variables on outcomes with durvalumab in unresectable Stage III NSCLC (PACIFIC)
AU - Faivre-Finn, Corinne
AU - Spigel, David R
AU - Senan, Suresh
AU - Langer, Corey
AU - Perez, Bradford A
AU - Özgüroğlu, Mustafa
AU - Daniel, Davey
AU - Villegas, Augusto
AU - Vicente, David
AU - Hui, Rina
AU - Murakami, Shuji
AU - Paz-Ares, Luis
AU - Broadhurst, Helen
AU - Wadsworth, Catherine
AU - Dennis, Phillip A
AU - Antonia, Scott J
N1 - Funding Information: Dr. Faivre-Finn reports grants and other from AstraZeneca, grants and other from Elekta , outside the submitted work; Dr. Spigel reports grants and other from AstraZeneca, during the conduct of the study; grants and other from Genentech/Roche , grants and other from Novartis , grants and other from Celgene , grants and other from Bristol-Myers Squibb , grants and other from AstraZeneca, other from Pfizer , other from Boehringer Ingelheim , other from AbbVie , other from Foundation Medicine , grants and other from GlaxoSmithKline , grants and other from Lilly , grants and other from Merck , other from Moderna Therapeutics, grants and other from Nektar , grants and other from Takeda , other from Amgen, other from TRM Oncology, other from Precision Oncology, other from Evelo Therapeutics, other from Illumina, other from PharmaMar, grants from University of Texas Southwestern Medical Center - Simmons Cancer Center , grants from G1 Therapeutics , grants from Neon Therapeutics , grants from Celldex , grants from Clovis Oncology , grants from Daiichi Sankyo , grants and other from EMD Serono , grants from Astellas Pharma , grants from GRAIL , grants from Transgene , grants from Aeglea Biotherapeutics , grants from Tesaro , grants from Ipsen , other from Aptitude Health, other from Bayer, other from Dracen Pharmaceuticals, other from Iksuda Therapeutics, other from Molecular Templates, other from Seattle Genetics, other from TRIPTYCH Health Partners, grants from Janssen , grants from MedImmune , grants from BIND Therapeutics , grants from Eisai , grants from ImClone Systems , other from Intellisphere, outside the submitted work; Dr. Senan reports grants and personal fees from AstraZeneca, personal fees from Celgene, personal fees from MSD , personal fees from Eli Lilly, grants and personal fees from Varian Medical Systems , grants from ViewRay Inc. , outside the submitted work; Dr. Langer reports personal fees from AstraZeneca, personal fees from Merck, personal fees from Genentech/Roche, personal fees from Hospira , personal fees from Gilead , personal fees from Lilly, personal fees from Amgen , personal fees from Lilly, grants from Merck, grants from Lilly, grants from Inovio , grants from Trizell , outside the submitted work; Dr. Perez reports personal fees from AstraZeneca, grants and personal fees from Bristol-Myers Squibb, outside the submitted work; Dr. Özgüroğlu has nothing to disclose; Dr. Daniel reports other from AstraZeneca during the conduct of the study; other from Boehringer Ingelheim, other from Genentech/Roche, other from Eli Lily, other from Celgene, other from Pfizer, other from G1 Therapeutics, outside the submitted work; Dr. Villegas reports personal fees from AstraZeneca, outside the submitted work; Dr. Vicente reports grants and personal fees from AstraZeneca, grants and personal fees from Pfizer, personal fees from Bristol-Myers Squibb, grants and personal fees from MSD, grants and personal fees from Roche, outside the submitted work; Dr. Hui reports personal fees from AstraZeneca, personal fees from Bristol-Myers Squibb, personal fees from Eli Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Roche, outside the submitted work; Dr. Murakami has nothing to disclose; Dr. Paz-Ares reports personal fees from MSD, grants and personal fees from BMS, personal fees from Roche, grants and personal fees from AstraZeneca, personal fees from Lilly, personal fees from Merck, personal fees from Novartis, personal fees from Amgen, personal fees from Incyte , personal fees from Takeda, personal fees from Blueprint , personal fees from Bayer , other from Altum Sequencing, personal fees and other from Genomica , personal fees and other from PharmaMar , personal fees and other from Ipsen, outside the submitted work; Ms. Broadhurst is an independent contractor, funded by AstraZeneca; Dr. Wadsworth was a full time employee of AstraZeneca when the work was completed; Dr. Dennis reports other from AstraZeneca, outside the submitted work; Dr. Antonia reports other from Bristol-Myers Squibb, other from Novartis, other from Merck, other from Boehringer Ingelheim, other from AstraZeneca/MedImmune, other from CBMG, other from Memgen, outside the submitted work. Funding Information: Medical writing support during the preparation of this manuscript, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, of Cirrus Communications (Manchester, UK), an Ashfield company, and was funded by AstraZeneca. Professor Corinne Faivre-Finn is supported by a grant from the NIHR Manchester Biomedical Research Centre . Funding Information: This study was funded by AstraZeneca (ClinicalTrials.gov: NCT02125461). Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Introduction: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. Methods: Patients were randomized 2:1 (1–42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60–66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. Results: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34–0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35–0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51–1.20]); carboplatin (0.86 [0.60–1.23]); vinorelbine (0.79 [0.49–1.27]); and taxane-based CT (0.73 [0.51–1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62–1.06]). Safety was broadly similar across the CRT subgroups. Conclusion: Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
AB - Introduction: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables. Methods: Patients were randomized 2:1 (1–42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60–66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models. Results: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34–0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35–0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51–1.20]); carboplatin (0.86 [0.60–1.23]); vinorelbine (0.79 [0.49–1.27]); and taxane-based CT (0.73 [0.51–1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62–1.06]). Safety was broadly similar across the CRT subgroups. Conclusion: Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
KW - Chemoradiotherapy
KW - Chemotherapy
KW - Immunotherapy
KW - Non-small-cell lung cancer
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85097251886&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.lungcan.2020.11.024
DO - https://doi.org/10.1016/j.lungcan.2020.11.024
M3 - Article
C2 - 33285469
SN - 0169-5002
VL - 151
SP - 30
EP - 38
JO - Lung Cancer
JF - Lung Cancer
ER -