Does SBRT Improve the Pembrolizumab Response Rate?
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.”
- 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]