Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Nov 1;9(11):1505-1513.
doi: 10.1001/jamaoncol.2023.3309.

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial

Motoko Tachihara  1 , Kayoko Tsujino  2 , Takeaki Ishihara  3 , Hidetoshi Hayashi  4 , Yuki Sato  5 , Takayasu Kurata  6 , Shunichi Sugawara  7 , Yoshimasa Shiraishi  8 , Shunsuke Teraoka  9 , Koichi Azuma  10 , Haruko Daga  11 , Masafumi Yamaguchi  12 , Takeshi Kodaira  13 , Miyako Satouchi  14 , Mototsugu Shimokawa  15 , Nobuyuki Yamamoto  9 , Kazuhiko Nakagawa  4 ; West Japan Oncology Group (WJOG)
Affiliations
Clinical Trial

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial

Motoko Tachihara et al. JAMA Oncol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Patient Flow Diagram
Figure 2.
Figure 2.. Progression-Free Survival (PFS) Since Second Registration by Independent Central Review
Median follow-up was 22.8 months; range, 4.3-31.8 months.
Figure 3.
Figure 3.. Waterfall Plot and Swimmer Plot for Individual Patients in the Full Analysis Set
Median follow-up was 22.8 months (range, 4.3-31.8 months). AE indicates adverse event.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 - DOI - PubMed
    1. National Cancer Institute Surveillance, Epidemiology and End Results Program. SEER cancer statistics review (CRS) 1975-2016. Updated April 9, 2020. Accessed July 14, 2023. (https://seer.cancer.gov/csr/1975_2016/.
    1. Goldstraw P, Chansky K, Crowley J, et al. ; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions . The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39-51. doi:10.1016/j.jtho.2015.09.009 - DOI - PubMed
    1. Zenke Y, Tsuboi M, Chiba Y, et al. . Effect of second-generation vs third-generation chemotherapy regimens with thoracic radiotherapy on unresectable stage III non–small-cell lung cancer: 10-year follow-up of a WJTOG0105 phase 3 randomized clinical trial. JAMA Oncol. 2021;7(6):904-909. doi:10.1001/jamaoncol.2021.0113 - DOI - PMC - PubMed
    1. Antonia SJ, Villegas A, Daniel D, et al. ; PACIFIC Investigators . Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017;377(20):1919-1929. doi:10.1056/NEJMoa1709937 - DOI - PubMed

Publication types

Associated data