Interim analysis from the multicenter ROSE study: Radiation during osimertinib treatment safety and efficacy cohort

BackgroundIn advanced EGFR mutated NSCLC third generation TKIs offer good CNS activity and favorable side effect profiles. Local therapy, and in particular radiation, may be used to treat oligoprogression and thus extend time on targeted therapy before chemotherapy is needed. Unfortunately, there is little consensus about the need to pause EGFR-TKIs during radiation therapy, leading to unnecessary treatment interruptions and potential diffuse disease progression. The ROSE study investigates the safety and efficacy of continuing osimertinib treatment during radiation to lung cancer lesions in the lung, brain, or bone/organs/soft tissues.MethodsThe prospective, multicenter ROSE study assesses the tolerability of radiation for EGFR mutated NSCLC during treatment with osimertinib. Osimertinib is dosed as per marketing authorization and radiation according to standard of care. The primary endpoint is safety and tolerability (CTCAE V5.0), including pneumonitis, radiation pneumonitis, radionecrosis and cardiac failure as adverse events of special interest.ResultsThis interim analysis followed the inclusion of 23 patients (final analysis at n= 40). Radiation to lung (n=15) or soft tissue/bone (n=8) lesions was mainly for oligoprogression. 74 % were female and the mean age was 66.7 years. At interim analysis osimertinib had been given for an average of 23,7 months including an average of 6,8 months following inclusion in the study. From start of radiation to 28 days after radiation there were five grade 3-4 AEs. Of these, two events in the same patient were possibly related to treatment (bone pain and hip fracture) following irradiation of a bone metastasis. The safety committee convened twice and unanimously recommended continuing recruitment.ConclusionsThese interim data show that radiation therapy during osimertinib is a safe and tolerable treatment with the potential to extend time on TKI treatment and postpone further lines of therapy. The ROSE study is ongoing and is planned to complete recruitment by the end of 2024.Clinical trial identificationEudraCT 2020-003512-27, NCT05089916 (submitted 2021-04-13, posted 2021-10-22).Legal entity responsible for the studyAIO Studien gGmbH.FundingThis research was sponsored by AIO-Studien-gGmbH and supported by a grant from AstraZeneca.DisclosureA. Tufman: Financial Interests, Personal, Advisory Board, IIT Funding for this trial: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Roche, Novartis, MSD, BMS, Boehringer Ingelheim, Janssen, Daiichi Sankyo, Amgen, Pierre Fabre, Sanofi; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Funding, Conference Support: Janssen, Daiichi Sankyo. F. Manapov: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Lilly, Elekta, Brainlab; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Funding, Conference Support: AstraZeneca, Elekta, Brainlab. W.M. Brueckl: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Boehringer Ingelheim, MSD, Lilly, BMS, Roche, Pfizer, Sanofi, Janssen, Amgen, Daiichi Sankyo; Financial Interests, Personal, Funding, Conference support: AstraZeneca, Amgen, Daiichi Sankyo. E.L. Buchmeier: Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca, BMS, Takeda; Financial Interests, Personal, Funding, Conference Support: Janssen. J. Stratmann: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, AstraZeneca, BMS, Oncopeptides, Amgen, LEO Pharma, Novartis, Takeda, Lilly, MSD/Merck, Sanofi, Pfizer. N. Frost: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Merck Serono, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Invited Speaker: Berlinchemie, Boehringer Ingelheim, Eli Lilly, MSD, Roche, Sanofi, Regeneron; Financial Interests, Personal and Institutional, Research Grant, ANTELOPE trial (NCT05689671): Roche; Non-Financial Interests, Leadership Role, Member of the steering board, section thoracic oncology: Working Group Medical Oncology within German Cancer Society (AIO). C. Schulz: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Novartis, MSD, BMS, Pfizer, Lilly, Takeda, Boehringer Ingelheim, Bayer, Amgen; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Chugai, AstraZeneca, MSD, BMS, Pfizer, Lilly, Takeda, Merck, Boehringer Ingelheim. J.K. Kern: Financial Interests, Institutional, Research Funding: AstraZeneca, Roche, MSD, BMS; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, Takeda, BMS, MSD, Novartis; Financial Interests, Personal, Funding, Conference support: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, BMS, MSD; Financial Interests, Personal, Funding, Confe5rence support: Janssen. T.C. Wehler: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Janssen, BMS, MSD, Merck, Pfizer, Roche, Novartis. R.M. Huber: Financial Interests, Personal, Advisory Board, 2022: Janssen, Merck, Boehringer Ingelheim, Sanofi; Financial Interests, Personal, Advisory Board, 2022, 2023: Novocure. D. Kauffmann-Guerrero: Financial Interests, Personal, Advisory Board: MSD, Boehringer Ingelheim, Janssen, Pfizer, BMS; Financial Interests, Personal, Invited Speaker: Roche. All other authors have declared no conflicts of interest.