Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiotherapy

Publication date: Available online 11 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Andrew Bang, Tyler J. Wilhite, Luke Pike, Daniel N. Cagney, Ayal A. Aizer, Allison Taylor, Alexander Spektor, Monica Krishnan, Patrick A. Ott, Tracy A. Balboni, F. Stephen Hodi, Jonathan D. Schoenfeld
PurposeImmune checkpoint inhibitors are increasingly used in the treatment of metastatic cancers and associated with immune-related adverse events (ir-AEs) such as pneumonitis. Many patients receiving these agents also receive palliative radiotherapy, yet data regarding the tolerability of combined treatment are sparse. We aimed to characterize potential toxicities and relevant risks.Methods and MaterialsWe retrospectively reviewed records from patients with metastatic non-small cell lung cancer, melanoma or renal cell cancer who received at least one cycle of a CTLA-4 or PD-1 inhibitor and radiation. Ir-AEs, defined using CTCAE v4.0, were tabulated in relation to treatment variables, and associations with sequencing and timing were assessed.ResultsWe identified 133 patients, of whom 28 received a CTLA-4 inhibitor alone, 88 received a PD-1 inhibitor alone and 17 received both classes of inhibitors either sequentially (n=13) or concurrently (n=4). Fifty-two patients received radiation within 14 days of an immune checkpoint inhibitor. Forty-eight patients experienced at least one ir-AE (34.6%). Patients receiving both CTLA-4 and PD-1 inhibitors experienced more any grade ir-AEs as compared to either individually (71% vs. 29%, p=0.0008). Any grade ir-AEs occurred in 39% of patients in whom radiation was administered within 14 days of immunotherapy compared with 23% of other patients (p=0.06) and more often in patients who received higher EQD2 (p=0.01). However, most toxicities were mild. There were no associations between site irradiated and specific ir-AEs.ConclusionsOur data suggests the combination of focal palliative radiation and CTLA-4 and/or PD-1 inhibitors is well-tolerated, with manageable ir-AEs that did not appear to be associated with the particular site irradiated. Although conclusions are limited by the heterogeneity of patients and treatments and future confirmatory studies are needed, this information can help guide clinical practice for patients on immune checkpoint therapy who require palliative radiotherapy.

Teaser

Metastatic cancer patients are increasingly treated with immune checkpoint inhibitors. We analyzed immune-related adverse events (ir-AEs) in 133 patients treated with radiation and immune checkpoint blockade. Although there was a trend towards an association between ir-AEs and radiation administered within 14 days of immunotherapy (39% vs. 23%, p=0.06), we didn't identify increases in serious ir-AEs or relationships between radiation fields encompassing the lung and bowel and specific ir-AEs such as pneumonitis and colitis.


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