Does SBRT Improve the Pembrolizumab Response Rate?

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Although checkpoint inhibition is altering the landscape of oncologic care, there is a low response rate to treatment.
Although checkpoint inhibition is altering the landscape of oncologic care, there is a low response rate to treatment.

Multisite stereotactic body radiotherapy (SBRT) followed by PD-1 inhibition with pembrolizumab may be an effective option for some patients with advanced solid tumors, according to a study published in the Journal of Clinical Oncology.1

Although checkpoint inhibition is altering the landscape of oncologic care, there is a low response rate to treatment. Findings from previous studies suggested that tumor debulking with SBRT may lead to increased responsiveness to PD-1 inhibition.

For this phase 1 study (ClinicalTrials.gov Identifier: NCT02608385), researchers assigned 73 patients with solid tumors who progressed on standard treatment to receive SBRT in 30 to 50 Gy doses over 3 to 5 fractions on 2 to 4 metastatic sites. Patients began intravenous pembrolizumab 200 mg within 1 week of SBRT completion. Pre- and post-SBRT tumor biopsies were performed on the same metastatic site to assess interferon (IFN)-γ-induced gene expression.

Sixty-nine patients received SBRT on 2 metastatic sites, 3 patients to 3 sites, and 1 patient to 4 sites; all patients received at least 1 cycle of pembrolizumab.

The median follow-up for toxicity was 5.5 months. There were no radiation-dose reductions, but 6 patients had severe dose-limiting treatment-related adverse events including pneumonitis, colitis, and hepatic toxicity.

The overall response rate was 13.2% among the 68 patients who had imaging follow-up. The median overall survival and progression-free survival was 9.6 months (95% CI, 6.5 months-not evaluable) and 3.1 months (95% CI, 2.9-3.4), respectively.

SBRT was associated with driving IFN-γ-associated gene expression in non-irradiated tumors (P = .023) compared with pre-SBRT biopsy samples.

The authors concluded that “additional studies exploring the clinical benefit and predictive biomarkers of combined multisite SBRT and PD-1–directed immunotherapy are warranted.”

Reference

  1. Luke JJ, Lemons JM, Karrison TG, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol. 2018 Feb 13. doi: 10.1200/JCO.2017.76.2229 [Epub ahead of print]

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