Abstract 4989: Toxicity profile of contemporaneous PD-1 inhibitor immunotherapy and radiotherapy
Authors: Wilhite Tyler J. , Chandra Ravi A. , Balboni Tracy A. , Taylor Allison , Aizer Ayal A. , Spektor Alexander , Ott Patrick A. , Hodi F. Stephen , Schoenfeld Jonathan D. 
Published: July 2016

Abstract
Purpose/Objectives: PD-1 inhibitors are approved for treatment of metastatic melanoma and non-small cell lung cancer (NSCLC) and under active investigation for treatment of metastatic renal cell carcinoma (RCC). Prior studies suggest that the majority of patients with these malignancies are likely to receive palliative radiotherapy at some point during their care. Growing preclinical and clinical evidence suggests that if delivered optimally, radiotherapy and immunotherapy may synergize. However, there is currently limited data on the safety of contemporaneous treatment with PD-1 inhibitors and radiotherapy and how this combination affects the risk of immune-related or radiotherapy-related adverse events. We aimed to evaluate toxicity in patients with metastatic melanoma, RCC, and NSCLC following contemporaneous treatment with PD-1 inhibitors and radiotherapy.
Materials/Methods: We retrospectively reviewed records from patients with metastatic melanoma, RCC, and NSCLC cancer treated with PD-1 inhibitors and palliative radiotherapy. To account for delayed immune/radiation-mediated effects, patients were included who received radiotherapy either within 75 days prior to a PD-1 inhibitor or within 75 days after. Patient demographics, treatment parameters, and immune-related (ir-AE) and radiotherapy-related adverse events were recorded using CTCAE v4.0.
Results: Fifteen patients (7 melanoma, 4 RCC, 4 NSCLC) underwent 23 courses of palliative radiotherapy and a median of 8 doses of PD-1 inhibition between 2011-2014. Median follow up from date of metastatic diagnosis was 32 months. Radiotherapy courses included both brain (n = 6)/non-brain (n = 17) and fraction sizes ranging from 3-8 Gy (total doses 8-36 Gy). Radiation was given 19-43 days prior to PD-1 inhibition (n = 7) or 30-75 days afterwards (n = 19). One patient completed a course of radiotherapy the same day as receiving PD-1 inhibition. Any grade immune-related adverse events were observed in 3 patients (20%). Only 1 of those 3 patients who had received radiation to the skull base was thought to have ir-AEs likely attributable to the PD-1 inhibitor (Grade 2 pericarditis, anemia, and rash). Radiation-related adverse events were observed in 1 patient (7%), who developed moderate mucositis and dysphagia following submandibular radiation to a dose of 30 Gy. No patients developed pneumonitis, despite 7 patients (47%) receiving radiation with fields that partially irradiated the lung.
Conclusions: In this early clinical experience, the contemporaneous receipt of PD-1 inhibitors and palliative radiotherapy did not seem to confer an increased risk of toxicity beyond the expected level associated with each independently. Thus, prospective studies to explore combined treatment with these modalities would likely be safe if undertaken.
Citation Format: Tyler J. Wilhite, Ravi A. Chandra, Tracy A. Balboni, Allison Taylor, Ayal A. Aizer, Alexander Spektor, Patrick A. Ott, F. Stephen Hodi, Jonathan D. Schoenfeld. Toxicity profile of contemporaneous PD-1 inhibitor immunotherapy and radiotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4989.