Interim Analysis of pulmonary tolerability from the multicenter ROSE Study: Radiation during Osimertinib Treatment Safety and Efficacy Cohort

<bold>Background:</bold> In advanced EGFR mutated NSCLC third generation TKIs offer good CNS activity and favorable side effect profiles. Radiation is used to treat oligoprogression, but there is little consensus about pausing TKIs during radiation to the lung, leading to unnecessary treatment interruptions. The ROSE study investigates the safety and efficacy of continuing osimertinib during radiation and includes a cohort with radiation to pulmonary lesions. <bold>Methods:</bold> The prospective, multicenter ROSE study assesses the tolerability of radiation during standard of care osimertinib. The primary endpoint is safety and tolerability (CTCAE V5.0), with a focus on pulmonary tolerability including pneumonitis and radiation pneumonitis as events of special interest. <bold>Results:</bold> This interim analysis included 35 patients; 74% female, mean age 66.3 years. Radiation to lung (n=22) or soft tissue/bone (n=13) lesions was mainly for oligoprogression. From start of radiation to 28 days after there were 11 grade 3 AEs. In the lung cohort there were two cases of suspected TKI-induced pneumonitis, one case of suspected radiation pneumonitis and a case of pulmonary fibrosis. The safety committee met three times and unanimously recommended continuing recruitment. Patients in the lung cohort received an average of 175 days of osimertinib on study, and an average of 723.5 days in total. <bold>Conclusion:</bold> These interim data show that radiation therapy to the lung during osimertinib is a safe and tolerable treatment with the potential to extend time on TKI treatment and postpone further lines of therapy.