Checkpoint Inhibitors With Radiotherapy in Patients With Advanced Solid Tumors

1. Stereotactic body radiotherapy in addition to immune checkpoint inhibitors has similar progression-free survival to immune checkpoint inhibitors alone, with HR 0.95.

2. Grade 3 and 4 acute treatment-related toxic effects occurred at similar rates across both groups (18% in each).

Evidence Rating Level: 1 (Excellent)

Study Rundown: The combination of immune checkpoint inhibitors (ICIs) and stereotactic body radiotherapy (SBRT) shows promise in improving treatment outcomes for patients with advanced solid tumors through inducing immunogenic cell death and triggering a systemic antitumor immune response, known as the abscopal effect. This study investigates whether the combination of ICIs and SBRT can enhance outcomes in patients with locally advanced or metastatic solid tumors. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS), objective response rate (ORR), local control of lesions (LCL), and safety. Median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm, with HR 0.95, and this effect was seen across prespecified strata for disease burden or tumor type. Median OS was 11.0 months in the control arm vs 14.3 months in the experimental arm, with HR 0.82. ORR was 22% vs 27% respectively. LCR of irradiated lesions was 75% in the experimental arm, with a complete response of irradiated lesions was seen in 33%. The most common adverse events included fatigue and pruritus. Grade 3 and 4 acute treatment-related toxic effects occurred in 18% of the control arm vs 18% in the experimental arm. The strength of this study comes from its methodology, and the limitations include the small sample size and the heterogeneity of the sample. Overall, this study found outcome measures in SBRT in addition to ICI did not significantly differ from ICI alone.

Click to read the study in JAMA Oncology

Relevant Reading: DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

In-Depth [randomized controlled trial]: This multicenter, phase 2 trial enrolled adults with histologically confirmed advanced HNSCC, melanoma, NSCLC, RCC or US who qualified for a PD-LI ICI and had at least 1 extracranial tumor amenable to radiotherapy and randomized them into receiving ICI therapy alone (52 patients) or combined ICI with SBRT (47). The choice of ICI was left to the investigator but could include nivolumab, pembrolizumab, or atezolizumab, and SBRT consisted of 3x8Gy every other day. Median PFS was 2.8 months (95%CI, 2.5-8.4) in the control arm compared with 4.4 months (95%CI, 2.8-7.8) in the experimental arm, with HR 0.95 (95%CI, 0.58-1.53; p=0.82), and this effect was seen across prespecified strata for disease burden or tumor type. Median OS was 11.0 months (95%CI, 9.0-NR) in the control arm vs 14.3 months (95%CI, 11.0-NR) in the experimental arm, with HR 0.82 (95%CI, 0.48-1.41; p=0.47). The post-hoc analysis found an association between the number of irradiated lesions and OS in the experimental arm with HR 0.31 (95%CI, 0.15-0.65, p=0.002). ORR was 22% vs 27% respectively (p=0.56). LCR of irradiated lesions was 75% in the experimental arm, with a complete response of irradiated lesions seen in 33%. The most common adverse events included fatigue and pruritus. Grade 3 and 4 acute treatment-related toxic effects occurred in 18% of the control arm vs 18% in the experimental arm. Overall, this study found outcome measures in SBRT in addition to ICI did not significantly differ from ICI alone.

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