Adverse Events in a Randomized Trial Comparing Radiation Therapy With or Without Olaparib for Inflammatory Breast Cancer.

purposeRecent conflicting reports regarding the tolerability of poly (ADP-ribose) polymerase (PARP) inhibitors administered concurrently with breast radiation therapy motivate analysis of adverse events reported in a large national cooperative group trial. METHODS AND MATERIALS: From May 2019 to June 2024, we enrolled patients with inflammatory (T4d) nonmetastatic breast cancer to a phase 2 NCI-cooperative group trial, which randomized patients after neoadjuvant systemic therapy selected by the treating physician and modified radical mastectomy to 2 arms. The control arm was assigned 50 Gy of chest wall and nodal radiation therapy, including bolus, plus 10-Gy boost. The intervention arm was assigned the same radiotherapeutic regimen with 25 mg of olaparib twice daily during radiation therapy. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v5.0 weekly during radiation therapy. This analysis explores the distribution of radiation dermatitis, all acute adverse events in the chest-wall region, and other adverse events through the end of radiation therapy by study arm, where the adverse events were deemed possibly, probably, or definitely treatment-related. χ

resultsAmong 146 evaluable participants (73 control, 73 intervention), median age was 54.1. No grade 4 or 5 treatment-related events were reported. Grade 3 radiation dermatitis was reported in 24.7% of patients in the intervention arm and 5.5% in the control arm (P = .003) during radiation therapy. When considering all acute chest-region adverse events, 24.7% had grade 3 acute adverse events in the intervention arm versus 6.8% in the control arm (P = .006) during treatment. One patient on the intervention arm had early, confluent telangiectasia throughout the 50-Gy fields with radiation-induced lichenoid dermatitis. Intervention arm patients were more likely to experience grade 2 or greater gastrointestinal adverse events (17.8% vs 0%, P < .001) and any grade of laboratory investigation abnormalities (19.2% vs 0%, P < .001).

conclusionsThis analysis suggests continued caution if considering concurrent administration of radiation therapy and olaparib outside of the investigational context.