PMID- 37676681 OWN - NLM STAT- MEDLINE DCOM- 20231128 LR - 20231128 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 9 IP - 11 DP - 2023 Nov 1 TI - Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. PG - 1505-1513 LID - 10.1001/jamaoncol.2023.3309 [doi] AB - IMPORTANCE: Administration of durvalumab after concurrent chemoradiotherapy is the standard treatment of unresectable, locally advanced non-small cell lung cancer (NSCLC); however, 20% to 30% of patients do not receive durvalumab because of adverse events (AEs) during concurrent chemoradiotherapy. In addition, radiotherapy and immunotherapy have a synergistic effect. OBJECTIVE: To investigate the efficacy and safety of durvalumab immunotherapy plus concurrent radiotherapy followed by maintenance with durvalumab therapy for treatment of locally advanced NSCLC without chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, single-arm DOLPHIN (Phase II Study of Durvalumab [MEDI4736] Plus Concurrent Radiation Therapy in Advanced Localized NSCLC Patients) nonrandomized controlled trial was performed by 12 institutions in Japan from September 13, 2019, to May 31, 2022. Participants in the primary registration phase included 74 patients with programmed cell death ligand 1 (PD-L1)-positive, unresectable, locally advanced NSCLC. The current analyses were conducted from June 1, 2022, to October 31, 2022. INTERVENTIONS: Patients received radiotherapy (60 Gy) in combination with concurrent and maintenance durvalumab immunotherapy, 10 mg/kg every 2 weeks, for up to 1 year. MAIN OUTCOMES AND MEASURES: The primary end point of the rate of 12-month progression-free survival (PFS), as assessed by an independent central review, was estimated using the Kaplan-Meier method and evaluated with 90% CIs calculated using the Greenwood formula. The key secondary end points were PFS, objective response rate, treatment completion rate, and AEs. RESULTS: Data from 35 patients (median [range] age, 72 [44-83] years; 31 [88.6%] men) were included in the full analysis set of the evaluable population. The 12-month PFS rate was 72.1% (90% CI, 59.1%-85.1%), and the median PFS was 25.6 months (95% CI, 13.1 months to not estimable) at a median follow-up of 22.8 months (range, 4.3-31.8 months). Scheduled radiation therapy was completed in 97.1% of patients. The confirmed objective response rate was 90.9% (95% CI, 75.7%-98.1%), and the treatment completion rate was 57.6% (95% CI, 39.2%-74.5%). Among 34 patients evaluated in the safety analysis set, AEs of grade 3 or 4 occurred in 18 patients (52.9%), and of grade 5 in 2 patients (5.9%). Pneumonitis or radiation pneumonitis of any grade occurred in 23 patients (67.6%), and of grades 3 or 4 in 4 patients (11.8%). CONCLUSIONS AND RELEVANCE: Findings from this phase 2 nonrandomized controlled trial indicate that durvalumab immunotherapy combined with curative radiotherapy for patients with PD-L1-positive, unresectable, locally advanced NSCLC is a promising treatment with tolerable AEs and is appropriate as a study treatment for phase 3 clinical trials. TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCT2080224763. FAU - Tachihara, Motoko AU - Tachihara M AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Tsujino, Kayoko AU - Tsujino K AD - Department of Radiation Oncology, Hyogo Cancer Center, Akashi, Japan. FAU - Ishihara, Takeaki AU - Ishihara T AD - Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Hayashi, Hidetoshi AU - Hayashi H AD - Department of Medical Oncology, Kindai University, Osakasayama, Japan. FAU - Sato, Yuki AU - Sato Y AD - Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. FAU - Kurata, Takayasu AU - Kurata T AD - Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan. FAU - Sugawara, Shunichi AU - Sugawara S AD - Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan. FAU - Shiraishi, Yoshimasa AU - Shiraishi Y AD - Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Teraoka, Shunsuke AU - Teraoka S AD - Internal Medicine III, Wakayama Medical University, Wakayama, Japan. FAU - Azuma, Koichi AU - Azuma K AD - Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. FAU - Daga, Haruko AU - Daga H AD - Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan. FAU - Yamaguchi, Masafumi AU - Yamaguchi M AD - Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. FAU - Kodaira, Takeshi AU - Kodaira T AD - Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan. FAU - Satouchi, Miyako AU - Satouchi M AD - Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. FAU - Shimokawa, Mototsugu AU - Shimokawa M AD - Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan. FAU - Yamamoto, Nobuyuki AU - Yamamoto N AD - Internal Medicine III, Wakayama Medical University, Wakayama, Japan. FAU - Nakagawa, Kazuhiko AU - Nakagawa K AD - Department of Medical Oncology, Kindai University, Osakasayama, Japan. CN - West Japan Oncology Group (WJOG) LA - eng PT - Clinical Trial, Phase II PT - Controlled Clinical Trial PT - Journal Article PT - Multicenter Study PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 RN - 0 (B7-H1 Antigen) RN - 28X28X9OKV (durvalumab) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - B7-H1 Antigen MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/radiotherapy MH - Chemoradiotherapy/adverse effects/methods MH - Disease-Free Survival MH - *Lung Neoplasms/drug therapy/radiotherapy MH - Neoplasm Staging MH - Adult MH - Middle Aged MH - Aged, 80 and over PMC - PMC10485744 COIS- Conflict of Interest Disclosures: Dr Tachihara reported receiving grants from AstraZeneca and personal fees from AstraZeneca during the conduct of the study; receiving grants from Eli Lilly Japan and Chugai Pharmaceutical outside the submitted work; and receiving personal fees from Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Taiho Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Bristol Myers Squibb, and Novartis Pharmaceuticals outside the submitted work. Dr Tsujino reported receiving personal fees from AstraZeneca outside the submitted work. Dr Hayashi reported receiving grants from AstraZeneca, Astellas Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Pfizer Japan, Bristol Myers Squibb, Eli Lilly Japan, Chugai Pharmaceutical, Daiichi Sankyo, Merck Serono, Merck Biopharma, Takeda Pharmaceutical, Taiho Pharmaceutical, SymBio Pharmaceuticals, AbbVie, inVentiv Health Japan, ICON Japan, Gritstone Oncology, Parexel International Corp, Kissei Pharmaceutical, EPS Corp, Syneos Health, Pfizer R&D Japan, A2 Healthcare Corp, Quintiles Inc, IQVIA Services Japan, EP-CRSU, Linical, Eisai, CMIC Shift Zero, Kyowa Hakko Kirin, Bayer Yakuhin, EPS International, and Otsuka Pharmaceutical outside the submitted work; receiving personal fees from Amgen, AstraZeneca, Boehringer Ingelheim Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Janssen Pharmaceutical, Merck Biopharma, MSD, Novartis Pharmaceuticals, Ono Pharmaceutical, and Takeda Pharmaceutical outside the submitted work; receiving consulting fees from AstraZeneca, Boehringer Ingelheim Japan, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Guardant Health, Pfizer Japan, Takeda Pharmaceutical, and Merck Biopharma outside the submitted work; and holding a patent for Sysmex. Dr Sato reported receiving personal fees from AstraZeneca during the conduct of the study; and receiving personal fees from Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Novartis, Pfizer, Taiho Pharmaceutical, Nippon Kayaku Bristol Myers Squibb, Eli Lilly & Co, Takeda, and Kyowa Kirin outside the submitted work. Dr Kurata reported receiving grants, personal fees, and honoraria from AstraZeneca during the conduct of the study; receiving grants from MSD, Bristol Myers Squibb, Amgen, Daiichi Sankyo, and Takeda outside the submitted work; and receiving personal fees from MSD, Chugai Honoraria, Bristol Myers Squibb, Pfizer Honoraria, Ono, Nippon Kayaku, Boehringer Ingelheim, and Takeda outside the submitted work. Dr Sugawara reported receiving personal fees from AstraZeneca during the conduct of the study; and receiving personal fees from Chugai Pharma, MSD, Ono Pharmaceutical, Bristol Myers Squibb, Takeda, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Eli Lilly Japan, Novartis, Kyowa Kirin, Nippon Kayaku, Merck, Amgen, AbbVie, Otsuka, Thermo Fisher Scientific, and Towa Pharmaceutical outside the submitted work. Dr Shiraishi reported receiving grants from Chugai Pharma outside the submitted work; and receiving personal fees from Chugai Pharma, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, and Taiho Pharmaceutical outside the submitted work. Dr Teraoka reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Ono Pharmaceutical, Pfizer R&D Japan, Taiho Pharmaceutical, and Thermo Fisher Scientific outside the submitted work. Dr Azuma reported receiving personal fees from AstraZeneca, MSD, Ono Pharmaceutical, Bristol Myers Squibb, and Chugai Pharmaceutical outside the submitted work. Dr Daga reported receiving personal fees from Chugai, AstraZeneca, and Eli Lilly Japan outside the submitted work. Dr Yamaguchi reported receiving personal fees from AstraZeneca, Novartis Pharma, Bristol Myers Squibb, and Chugai Pharma during the conduct of the study. Dr Kodaira reported receiving personal fees from AstraZeneca, Ono Pharmaceutical, Takeda, Otsuka, and Merck Biopharma outside the submitted work. Dr Satouchi reported receiving grants and personal fees from AstraZeneca during the conduct of the study; grants from MSD, Taiho Pharmaceutical, Pfizer, Bristol Myers Squibb, GlaxoSmithKline, Novartis, Amgen, AbbVie, Takeda, Daiichi Sankyo, and Janssen outside the submitted work; and receiving personal fees from Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Pfizer, Boehringer Ingelheim, Bristol Myers Squibb, Ono Pharmaceutical, Novartis, MSD, Eisai Merck, Amgen, and Bayer outside the submitted work. Dr Yamamoto receiving reported grants from AstraZeneca during the conduct of the study; receiving grants from Eli Lilly Japan, MSD, Boehringer Ingelheim Japan, Chugai Pharmaceutical, and AstraZeneca outside the submitted work; and receiving personal fees from AstraZeneca, Boehringer Ingelheim Japan, Chugai Pharmaceutical, MSD, Taiho Pharmaceutical, Daiichi-Sankyo, Merck Biopharma, Ono Pharmaceutical, Takeda Pharmaceutical, and Eli Lilly Japan outside the submitted work. Dr Nakagawa reported receiving grants from AstraZeneca, MSD, Chugai Pharmaceutical Co, and Ono Pharmaceutical during the conduct of the study; receiving personal fees from Ono Pharmaceutical, AstraZeneca, Chugai Pharmaceutical, and MSD during the conduct of the study; receiving grants from Labcorp Development Japan, Japan Clinical Research Operations, Takeda Pharmaceutical, GlaxoSmithKline, Sanofi, Ascent Development Services, Nippon Boehringer Ingelheim, Amgen, Novartis Pharma, Otsuka Pharmaceutical, SRL Pharma, Pfizer R&D Japan, Bayer Yakuhin, Sysmex Corporation, Eisai, Mochida Pharmaceutical, Eli Lilly Japan, Medical Research Support, Parexel International Corp, PRA Health Sciences, EPS Corporation, Kissei Pharmaceutical, EPS International, Daiichi Sankyo, PPD-SNBL, SymBio Pharmaceuticals, IQVIA Services Japan, Syneos Health, Nippon Kayaku, EP-CRSU, Mebix, Bristol Myers Squibb, Janssen Pharmaceutical, CMIC Group, Shionogi & Co, Astellas Pharma, and Kobayashi Pharmaceutical outside the submitted work; receiving personal fees from Amgen, Nippon Kayaku, Eli Lilly Japan, Pfizer Japan, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Bayer Yakuhin, CMIC ShiftZero, Life Technologies Japan, Neo Communication, Daiichi Sankyo, Incyte Biosciences Japan, Merck Biopharma, Kyowa Kirin, Takeda Pharmaceutical, 3H Clinical Trial, Care Net, Medical Review, Medical Mobile Communications, Yodosha, Nikkei Business Publications, Japan Clinical Research Operations, CMIC Group, Novartis Pharma, TAIYO Pharma, Bristol Myers Squibb, and Janssen Pharmaceutical outside the submitted work; and holding a patent for Daiichi Sankyo. No other disclosures were reported. EDAT- 2023/09/07 12:42 MHDA- 2023/11/17 15:28 PMCR- 2024/09/07 CRDT- 2023/09/07 11:33 PHST- 2024/09/07 00:00 [pmc-release] PHST- 2023/11/17 15:28 [medline] PHST- 2023/09/07 12:42 [pubmed] PHST- 2023/09/07 11:33 [entrez] AID - 2809271 [pii] AID - coi230043 [pii] AID - 10.1001/jamaoncol.2023.3309 [doi] PST - ppublish SO - JAMA Oncol. 2023 Nov 1;9(11):1505-1513. doi: 10.1001/jamaoncol.2023.3309.