Adverse Events in a Randomized Trial Comparing Radiotherapy with or without Olaparib for Inflammatory Breast Cancer
Reshma Jagsi1, Allison Meisner2, Pavani Chalasani3
1Emory University, Atlanta, GA, USA; University of Michigan, Ann Arbor, MI, USA.
Introduction:
Recent conflicting reports regarding the tolerability of PARP inhibitors administered concurrently with breast radiotherapy motivate analysis of adverse events reported in a large national cooperative group trial.
Methods:
From 05/19 to 06/24, we enrolled patients with inflammatory (T4d) non-metastatic 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 two arms. The control arm was assigned 50 Gy of chest wall and nodal radiotherapy, including bolus, plus 10 Gy boost. The intervention arm was assigned the same radiotherapeutic regimen with 25 mg of olaparib twice daily during radiotherapy. Adverse events were assessed using the CTCAE v5.0 weekly during radiotherapy. 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 radiotherapy by study arm, where the adverse events were deemed possibly, probably, or definitely treatment-related. Chi-squared tests were used to compare proportions.
Results:
Among 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=0.003) during radiotherapy. When considering all acute chest-region adverse events (Table), 24.7% had grade 3 acute adverse events in the intervention arm vs 6.8% in the control arm (p=0.006) 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<0.001) and any grade of laboratory investigation abnormalities (19.2% vs 0%, p<0.001).
Conclusion:
This analysis suggests continued caution if considering concurrent administration of radiotherapy and olaparib outside of the investigational context.