Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study.

Background and Purpose: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab.
Materials and Methods: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis.
Results: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab.
Conclusion: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.
Competing Interests: Conflict of Interest statement Yoko Tsukita reports personal fees from AstraZeneca and Chugai Pharmaceutical outside the submitted work. Takaya Yamamoto reports personal fees from AstraZeneca outside the submitted work. Hiroshi Mayahara reports personal fees from Accuray Japan Inc., Hitachi, Ltd, Eisai Co., Ltd., grants from MSD, grants and personal fees from AstraZeneca plc outside the submitted work. Akito Hata reports grants and personal fees from Eli Lilly, Boehringer Ingelheim and Astrazeneca, personal fees from Chugai, grants from MSD outside the submitted work. Yuichiro Takeda reports grants from Chugai and Boehringer Ingelheim, personal fees from Otsuka Pharmaceutical Co., Ltd outside the submitted work. Junji Uchida reports personal fees from Astra Zeneca K.K., Chugai pharmaceutical.co.ltd, Bristol Myers Squibb, Taiho Pharma and Boehringer Ingelheim outside the submitted work. Kazuhiro Usui reports personal fees from Astra Zeneca, Chugai, MSD, Pfizer and Boehringer Ingelheim outside the submitted work. Motohiro Tamiya reports grants and personal fees from Boehringer Ingelheim, Ono Pharmaceutical and Bristol-Myers Squibb, personal fees from Chugai Pharmaceutical, MSD, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Asahi Kasei Pharmaceutical and Pfizer outside the submitted work. Yuko Oya reports personal fees from Chugai pharma, Boehringer Ingelheim, Daiichi Sankyo, Astrazeneca, Ono pharmaceutical and Eli lilly outside the submitted work. Takeshi Kodaira reports personal fees from Merck Serono Co., Hitachi Co., Bristle Myers Squibb., Accuray Co., Elekta Co., Ono Pharmaceutical Co., AstraZeneca Co., Taiho Pharmaceutical Co. and Canon Co. outside the submitted work. Eisaku Miyauchi reports grants and personal fees from Chugai pharmaceutical co ltd, Ono pharmaceutical co., ltd., Boehringer Ingelheim and Lilly, personal fees from Astrazeneca, Taiho pharma, Kyowa kirin, Daiichi sankyo, MSD, Bristol-Meyers Squibb, Novartis and Merck Bio outside the submitted work. Keiichi Jingu reports personal fees from Varina Medical Systems, Inc., Elekta K.K., Shimadzu Medical Systems Corporation, AstraZeneca K.K., Guerbet Japan and grants and personal fees from Eisai Co., Ltd., grants from Takeda Pharmaceutical Company Limited, TAIHO Phamaceutical Co., Ltd., outside the submitted work. The remaining authors declare no conflict of interest.
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