Multicenter evaluation of the tolerability of combined treatment with PD-1 and CTLA-4 immune checkpoint inhibitors and palliative radiotherapy
Menée à partir de données portant sur 133 patients atteints d'un cancer du poumon métastatique non à petites cellules, d'un mélanome ou d'un cancer à cellules rénales, cette étude multicentrique évalue la tolérabilité d'un traitement combinant radiothérapie et inhibiteurs de point de contrôle immunitaire ciblant PD-1 et CTLA-4
Purpose : Immune 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 Materials : We 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. Results : We 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. Conclusions : Our 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.