Lung Cancer. 2024;190:107530.
Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III non-small-cell lung cancer: Results from the phase 1 CLOVER study.
제1저자 김동완 · 교신저자 김동완
소속 (15)
- Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: kimdw@snu.ac.kr.
- Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Millenium Oncology, Houston, TX, USA.
- Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- Chang-Gung Medical Foundation Linkou, Taoyuan City, Taiwan.
- School of Medicine and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
- Hospital General Universitario Gregorio Marañón, Instituto de Investigacion Sanitaria Gregorio Marañón, Madrid, Spain.
- Taipei Veterans General Hospital, Taipei, Taiwan.
- UGC Intercentros Oncología Hospital Regional y Virgen de la Victoria, Málaga, Spain.
- Hospital Germans Trias i Pujol, Barcelona, Spain.
- University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
- AstraZeneca, Cambridge, UK.
- AstraZeneca, Gaithersburg, MD, USA.
- University of Arizona Cancer Center, Tucson, AZ, USA.
Abstract
INTRODUCTION For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort.
METHODS CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability.
RESULTS Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76.6 % of patients overall; the most common were neutropenia (51.6 %), leukopenia (20.3 %), and anemia (17.2 %). In a post-hoc analysis, 7.8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60.9 % (95 % confidence interval [CI], 47.9-72.9); median duration of response was 15.8 months (95 % CI, 9.0-not estimable [NE]). Median progression-free survival was 13.4 months (95 % CI, 8.8-20.1) and median overall survival was not reached (95 % CI, 21.9-NE).
CONCLUSION Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC.
Copyright © 2024. Published by Elsevier B.V.
Keywords
Concurrent chemoradiotherapyDurvalumabPhase 1 studyStage III NSCLCUnresectable
Conflict of interest statement
Declaration of competing interest Dong-Wan Kim reports research funding (to institution) from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan, reports uncompensated consultation or advisory roles for Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Meck, MSD, NoveltyNobility, Oncobix, Pfizer, SK Biopharm, and Takeda, and has received medical writing assistance from Amgen, AstraZeneca, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Janssen, Merus, Mirati Therapeutics, MSD, Meck, Novartis, Pfizer, Roche, Takeda, and Yuhan. Byoung Chul Cho is an employee of Yonsei University Health System, reports stock/share ownership in TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., and J INTS BIO, reports advisory council or committee membership for KANAPH Therapeutic Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotec Inc, is a member of the board of directors for Interpark Bio Convergence Corp., and J INTS BIO, is an invited speaker for ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, and Pfizer, is a consultant for Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Takeda, MSD, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi, reports grants or funds from MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, and CHA Bundang Medical Center, reports royalties from Champions Oncology, Crown Bioscience, and Imagen, and is a founder of DAAN Biotherapeutics. Sang-We Kim reports advisory meeting participation for AstraZeneca, Amgen, Boehringer Ingelheim, Janssen, Novartis, Takeda, Therapex, and Yuhan, lecture fees from Boehringer Ingelheim, and research funding from Yuhan. Gee-Chen Chang reports honoraria from F. Hoffmann–La Roche, Ltd, Eli Lilly and Company Oncology, AstraZeneca, Novartis, Pfizer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Merck Sharp & Dohme. Myung-Ju Ahn reports advisory council or committee membership for AstraZeneca, YUHAN, Roche, Pfizer, Amgen, Merck, Takeda, Alpha Pharmaceutical, and VORONOI. Rosa Alvarez reports advisory council or committee membership for Astra Zeneca, Pharmamar, Boehringer Ingelheim, Novartis, Sanofi, and GSK, reports research funding (to institution) from PharmaMar, Astra Zeneca, Rain Therapeutics, GSK, Boehringer Ingelheim, Cebiotex, Roche, Philogen, MSD, Janssen, Pfizer, Daichii Sankyo, Gilead, and Seagen, speaker fees from Pharmamar, and travel support from Roche and Pharmamar. Chao-Hua Chiu reports honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Shionogi, and Takeda. José Trigo reports consulting fees from AstraZeneca, MSD, Eisai, and BMS. Ana Estiva reports advisory council or committee membership for Takeda, Roche, and MSD, and honoraria from Pfizer, MSD, Roche, Takeda, Pharmamar, and GSK. Sana D. Karam reports grants or funds from AstraZeneca (clinical trial), Genentech (clinical trial), and Roche (preclinical). Cathy O’Brien is a contractor for AstraZeneca. Hema Gowda is an employee of AstraZeneca, and reports stock/share ownership in AstraZeneca and Incyte. Haiyi Jiang reports employment and stock/share ownership with AstraZeneca. Julie E. Bauman reports consulting fees from BluedotBio and Exelixis. Krishna Pachipala and Chih-Liang Wang do not have any competing interests to disclose.
그 밖의 정보
- 출판 형태
- Clinical Trial, Phase I, Journal Article
- 저널
- Lung cancer (Amsterdam, Netherlands) · eISSN 1872-8332
- 전자 출판
- 2024-03-07
- MeSH
- Humans · Carcinoma, Non-Small-Cell Lung* / drug therapy · Lung Neoplasms* / drug therapy · Cisplatin / therapeutic use · Carboplatin · Paclitaxel · Chemoradiotherapy / methods · Neoplasm Staging · Antibodies, Monoclonal*
- Substances
- durvalumab · Cisplatin · Carboplatin · Paclitaxel · Antibodies, Monoclonal