Synergistic effects of Radiotherapy and Immune Checkpoint Inhibitors in Cancer Treatment

Abstract

Background: Use of immune checkpoint inhibitors have improved survival in patients suffering from cancer types such as advanced melanoma and NSCLC. Through increased understanding of immunological reactions associated with radiotherapy, a potential for synergy of radiotherapy and immune checkpoint inhibitors has emerged. Preclinical proof-of-concept studies have confirmed synergy of the treatments in mouse models.

Objectives: The primary objective was to identify proof-of-concepts in human data supporting combinations of radiotherapy and immune checkpoint inhibition, and identify characteristics of potential examples. A secondary objective was to assess if larger patient materials supported synergistic effects of such treatment regimens.

Methods: A literature search in PubMed was conducted to identify original data on patients treated with combinations of radiotherapy and immune checkpoint inhibition.

Results and discussion: Six case reports described impressive treatment responses following radiotherapy and immune checkpoint inhibition. A large double blinded RCT, including 799 patients, failed to present evidence for improved median survival in metastatic castration resistant prostate cancer (11,2 months for radiotherapy and Ipilimumab vs. 10,0 months for radiotherapy and placebo). Seven retrospective studies on patients (n=200) with advanced melanoma showed median survival over the expected, while two (n=38) failed to do so. Three of the retrospective studies specifically looked radiographically for abscopal responses outside the irradiated field, noting unusually frequent responses. A single small prospective trial (n=22) on advanced melanoma did not find a median survival over the expected. The studies varied in characteristics of the patient populations, methodologies and in radiotherapy regimens.

Conclusion: Case reports and retrospective studies investigating abscopal responses after radiation presented circumstantial evidence for synergy of radiotherapy and immune checkpoint inhibition. The single identified randomized controlled trial failed to prove increased survival of a relevant combination regimen in metastatic castration resistant prostate cancer, while retrospective studies in advanced melanoma were more encouraging.