@article{f18fa16f4c664b6dbe1bc9d91e8a1088,
title = "Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy",
abstract = "Introduction: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. Methods: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. Results: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. Conclusions: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.",
keywords = "Concurrent chemoradiotherapy, Durvalumab, EGFR TKI, EGFR mutation, Osimertinib",
author = "Aredo, {Jacqueline V.} and Isa Mambetsariev and Hellyer, {Jessica A.} and Arya Amini and Neal, {Joel W.} and Padda, {Sukhmani K.} and McCoach, {Caroline E.} and Riess, {Jonathan W.} and Cabebe, {Elwyn C.} and Jarushka Naidoo and Tariq Abuali and Ravi Salgia and Loo, {Billy W.} and Maximilian Diehn and Han, {Summer S.} and Wakelee, {Heather A.}",
note = "Funding Information: Disclosure: Dr. Neal reports receiving personal fees from Research to Practice, MLI PeerView, Medscape, Biomedical Learning Institute, Prime Oncology, Rockpointe, CME Matters, MJH CME, AstraZeneca, Jounce Therapeutics, Eli Lilly and Company, Calithera Biosciences, Amgen, Iovance Biotherapeutics, and UpToDate; grants and personal fees from Genentech/Roche, Exelixis, and Takeda Pharmaceuticals; and grants from Merck, Novartis, Boehringer Ingelheim, Nektar Therapeutics, Adaptimmune Therapeutics plc, and GlaxoSmithKline, all outside of the submitted work. Dr. Padda reports receiving personal fees from Pfizer, G1 Therapeutic, Blueprint, AstraZeneca, and G1 Therapeutic; grants from EpicentRx, Bayer, Boehringer Ingelheim, and 47 Inc.; and personal fees and other fees from AstraZeneca, all outside of the submitted work. Dr. McCoach reports receiving personal fees from Genentech and Guardant Health; grants from Revolution Medicines; and grants and personal fees from Novartis, all outside of the submitted work. Dr. Riess reports receiving personal fees from Blueprint, Celgene, Loxo Oncology, Genentech, and Medtronic; personal fees and nonfinancial support from Novartis, Boehringer Ingelheim, and Spectrum; and nonfinancial support from AstraZeneca, Merck, and Revolution Medicines, all outside of the submitted work. Dr. Naidoo reports receiving personal fees from Bristol-Myers Squibb, Roche/Genentech, Pfizer, Takeda, and Daiichi Sankyo; grants and personal fees from AstraZeneca and Bristol-Myers Squibb; and grants and other fees from Merck, all outside of the submitted work. Dr. Salgia reports receiving grants from the National Cancer Institute of the National Institutes of Health; personal fees from AstraZeneca and Merck; and other fees from Janssen and Novartis, all outside of the submitted work. Dr. Loo reports receiving research support from Varian Medical Systems outside of the submitted work and is a board member of TibaRay. Dr. Diehn reports receiving personal fees from Roche, AstraZeneca, BioNTech, RefleXion, and Gritstone Oncology; grants from Varian Medical Systems; personal fees and nonfinancial support from Illumina; and other fees from CiberMed and Foresight Diagnostics, all outside of the submitted work. In addition, Dr. Diehn has a patent related to cancer biomarkers with royalties paid to Roche and Foresight Diagnostics. Dr. Wakelee reports receiving personal consulting fees from Janssen, Daiichi Sankyo, Helsinn, Mirati, AstraZeneca, and Blueprint and grants to institution for clinical trial conduct from ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene, Clovis Oncology, Exelixis, Eli Lilly, Pfizer, and Pharmacyclics, all outside of the submitted work. The remaining authors declare no conflict of interest. Funding Information: Disclosure: Dr. Neal reports receiving personal fees from Research to Practice, MLI PeerView, Medscape, Biomedical Learning Institute, Prime Oncology, Rockpointe, CME Matters, MJH CME, AstraZeneca , Jounce Therapeutics, Eli Lilly and Company, Calithera Biosciences, Amgen , Iovance Biotherapeutics, and UpToDate; grants and personal fees from Genentech/Roche, Exelixis, and Takeda Pharmaceuticals; and grants from Merck , Novartis , Boehringer Ingelheim, Nektar Therapeutics, Adaptimmune Therapeutics plc, and GlaxoSmithKline, all outside of the submitted work. Dr. Padda reports receiving personal fees from Pfizer , G1 Therapeutic, Blueprint, AstraZeneca , and G1 Therapeutic; grants from EpicentRx, Bayer, Boehringer Ingelheim, and 47 Inc.; and personal fees and other fees from AstraZeneca, all outside of the submitted work. Dr. McCoach reports receiving personal fees from Genentech and Guardant Health; grants from Revolution Medicines; and grants and personal fees from Novartis, all outside of the submitted work. Dr. Riess reports receiving personal fees from Blueprint, Celgene, Loxo Oncology, Genentech , and Medtronic; personal fees and nonfinancial support from Novartis , Boehringer Ingelheim, and Spectrum; and nonfinancial support from AstraZeneca , Merck , and Revolution Medicines, all outside of the submitted work. Dr. Naidoo reports receiving personal fees from Bristol-Myers Squibb, Roche/Genentech, Pfizer, Takeda, and Daiichi Sankyo; grants and personal fees from AstraZeneca and Bristol-Myers Squibb; and grants and other fees from Merck, all outside of the submitted work. Dr. Salgia reports receiving grants from the National Cancer Institute of the National Institutes of Health; personal fees from AstraZeneca and Merck ; and other fees from Janssen and Novartis, all outside of the submitted work. Dr. Loo reports receiving research support from Varian Medical Systems outside of the submitted work and is a board member of TibaRay. Dr. Diehn reports receiving personal fees from Roche, AstraZeneca, BioNTech, RefleXion, and Gritstone Oncology; grants from Varian Medical Systems; personal fees and nonfinancial support from Illumina; and other fees from CiberMed and Foresight Diagnostics, all outside of the submitted work. In addition, Dr. Diehn has a patent related to cancer biomarkers with royalties paid to Roche and Foresight Diagnostics. Dr. Wakelee reports receiving personal consulting fees from Janssen, Daiichi Sankyo, Helsinn, Mirati, AstraZeneca, and Blueprint and grants to institution for clinical trial conduct from ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene, Clovis Oncology, Exelixis, Eli Lilly , Pfizer , and Pharmacyclics, all outside of the submitted work. The remaining authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2021 International Association for the Study of Lung Cancer",
year = "2021",
month = jun,
doi = "10.1016/j.jtho.2021.01.1628",
language = "English (US)",
volume = "16",
pages = "1030--1041",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "6",
}