Abstract 676P
Background
Combining radiotherapy and immunotherapy may induce stronger anti-tumor immunity. The present, multi-center, single-arm, phase II study aimed to prospectively evaluate whether performing chest radiotherapy prior to nivolumab + ipilimumab + chemotherapy can enhance the efficacy of the latter.
Methods
Patients with previously untreated stage IV non-small cell lung cancer (NSCLC) with a performance status of 0 or 1 were enrolled and received lung stereotactic body radiotherapy (24Gy in 3fractions) followed by nivolumab + ipilimumab + chemotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) at six months as assessed radiologically by an independent, blinded reviewer. The secondary endpoints included PFS, overall survival (OS), the objective response rate (ORR), PFS and OS at 1 year, and safety.
Results
Between June 2022 and September 2023, ten patients were enrolled; of these, eight were male. The median age was 70 years (range: 52-77). The histological types were adenocarcinoma, squamous cell carcinoma, and other in seven, two, and one patient, respectively. PD-L1 expression was > 50%, 1-49%, < 1%, and unknown in one, six, two, and one patient, respectively. Nine patients completed radiotherapy and received nivolumab + ipilimumab + chemotherapy. The PFS at six months was 44.4% (95% confidence interval (CI): 18.8-73.4). Five patients were able to continue treatment after the cut-off date. The median PFS and OS were not achieved at the median follow-up of 11.2 months. The ORR was 80% (95% CI: 47.9-95.4). Grade 3 or worse immune-related adverse events, which were observed eight times in four patients, included colitis (n=2), cytokine release syndrome (CRS) (n=2), rash (n=1), liver dysfunction (n=2), and diabetes (n=1). One patient died from CRS resulting from the treatment. Pneumonitis developed in three patients, but all were Grade 2 or less. This study was terminated early for safety reasons.
Conclusions
Nivolumab + ipilimumab + chemotherapy after lung stereotactic body radiotherapy may be effective as first-line therapy for stage IV NSCLC, but its safety needs further investigation.
Clinical trial identification
jRCTs031210688.
Editorial acknowledgement
Legal entity responsible for the study
North East Japan Study Group.
Funding
Ono Pharmaceutical.
Disclosure
K. Watanabe: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Chugai Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical Company, MSD K.K., Bristol Myers Squibb, Amgen, Pfizer, Novartis Pharma, Taiho Pharma, Merck BioPharma, sysmex corporation; Financial Interests, Personal, Advisory Board: Guardant Health, Inc.; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb. K. Ito: Financial Interests, Personal, Speaker’s Bureau: Varian Medical Systems K. K. T. Sumi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical CO., LTD., AstraZeneca, Nippon Boehringer Ingelheim Co., Ltd. K. Kaira: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Bristol Myers Squibb Company, Chugai Pharmaceutical Co. Ltd., Ono Pharmaceutical Company. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca K.K., Bristol Myers Squibb Company, Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Sanofi K.K. H. Kagamu: Financial Interests, Personal, Advisory Role: ImmuniT Research, Inc.; Financial Interests, Personal, Funding: Boehringer Ingelheim, Inc., Chugai Pharm. Inc, Taiho pharm. Inc., Ono Pharm. Inc.; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceuticals. Inc., AstraZeneca Inc., Bristol Myers Squibb Inc., Ono Pharm. Inc. K. Kobayashi: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, UCB Japan; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Research Funding: Zeria Pharmaceutical Co.; Financial Interests, Personal, Royalties: Japanese patent # 7422498. Y. Hosomi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda; Financial Interests, Personal, Advisory Board: Novartis, Pfizer. All other authors have declared no conflicts of interest.