No benefit to adding limited radiation in advanced cancer

TOPLINE:

Irradiating a small number of metastatic lesions does not appear to improve progression-free or overall survival in patients receiving immune checkpoint inhibitor monotherapy for advanced cancer.

METHODOLOGY:

• In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
• Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
• Most patients had more than three lesions.
• Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.

TAKEAWAY:

• Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
• Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
• However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
• The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.

IN PRACTICE:

Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.

SOURCE:

The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.

LIMITATIONS:

• There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
• More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.

DISCLOSURES:

The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.

Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.

A version of this article first appeared on Medscape.com.