Faculty, Staff and Student Publications

Language

English

Publication Date

6-1-2023

Journal

Radiotherapy & Oncology

DOI

10.1016/j.radonc.2023.109618

PMID

36921766

Abstract

Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900).

Methods and materials: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy in 10 fractions, considering the tumor location. The OS rates at 12, 36, and 60 months were estimated by the Kaplan-Meier method; subgroup analyses of progression-free survival (PFS) and OS by SABR-targeted lesions (liver/lung) were performed by log-rank tests.

Results: A total of 106 patients were enrolled in this long-term follow-up analysis. At the median follow-up time of 15.32 months (range, 0.97-82.13 months), the median PFS was 6.52 months (95% CI, 5.86-7.14) and the median OS was 15.32 months (95% CI,13.03-17.23). The 12-, 36-, and 60-month OS rates were 61%, 23%, and 15%, respectively. There was a significant difference in OS between cohorts (P = 0.039), with a stronger response observed in lung-treated subgroups. Patients who had received sequential fractions (50 Gy/4f) to the lung had improved OS compared to those who had received sequential fractions (18.29 vs 8.9 months, P = 0.043) to the liver. Subgroup analysis of SABR-targeted lesions showed that lung-targeted groups had significantly longer PFS (6.87 months vs. 5.63 months, P = 0.034) and OS (18.67 months vs. 13.63 months, P = 0.013) compared to liver-targeted groups. The sequence did not affect the outcomes of PFS and OS. Exploratory analyses showed that SABR-targeted lesions and smoking history comprised an independent risk factor for OS.

Conclusions: Updated 5-year OS data from the phase II trial demonstrate the long-term clinical benefit of ipilimumab and SABR, which warrants further research and cumulative data.

Keywords

Humans, Ipilimumab, Liver Neoplasms, Lung, Lung Neoplasms, Neoplasms, Second Primary, Radiosurgery, Treatment Outcome, Absolute lymphocyte count (ALC), Checkpoint inhibitor, Metastasis, Progression-free survival, Radiotherapy, Stereotactic ablative radiotherapy (SABR)

Published Open-Access

yes

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