According to a recent Phase I study, outcomes of patients with advanced solid tumors and multiple metastatic sites may be improved by treatment with multisite stereotactic body radiotherapy (SBRT) prior to treatment with the anti-PD-1 immunotherapeutic drug, pembrolizumab. The study demonstrated the combination was generally well-tolerated and resulted in abscopal responses.
SBRT has previously been shown to stimulate innate and adaptive immune responses, which is thought to enhance immunotherapy. Jeffrey Lemons of the University of Chicago (IL, USA) explained during Session 3 of the 2018 ASCO-SITC Clinical Immuno-Oncology Symposium (January 25–27; CA, USA) that responses to the anti-PD-1 drug appeared to correspond with interferon-gamma and that a lower disease burden will improve anti-PD-1 treatment outcomes.
Lemons also explained that an advantage to SBRT is the ability to “focus radiation beams to deliver high radiation doses while minimizing [exposure] to surrounding organs at risk.”
The study was conducted with patients with metastatic tumors who progressed on standard treatment. The metastases were amenable to SBRT and had 0.25 to 65 cc of viable tumor. SBRT was used to target two to four lesions per person, but not all sites of disease. The doses of SBRT varied from 30 Gy in three fractions to 50 Gy in five fractions and therapy with pembrolizumab was initiated 7 days following the final SBRT treatment.
A total of 151 metasteses were treated with SBRT, with most patients receiving this at two sites. The lesions treated were largely in the peripheral or central lung, abdomen/pelvis or the liver.
An overall objective response rate of 13.5% was observed in the 68 (out of a study of 79) patients who had imaging follow-up. In 36 of the patients neither the irradiated nor non-irradiated lesions progressed and in 15 patients the non-irradiated lesions progressed but the ones that had been treated with SBRT did not. In one patient, it was seen that the irradiated lesions progressed but the non-irradiated did not. The average change in diameter of the tumor was -21.7% for lesions treated with SBRT, compared with 1.7% for those not treated with SBRT.
“Multiorgan site SBRT followed by pembrolizumab was safe with no radiation dose reductions,” explained Lemons. “This is the first and largest prospective trial to determine the safety of this combination.”
Lemons also speculated possibilities for the mechanism behind SBRT’s potential enhancement of anti-PD-1 therapy, including tumor antigen release, improved antigen presentation and T-cell function, increased T-cell infiltration and modulation of immunosuppressive cell populations.
“This is a large, well-done study,” Ravindra Uppaluri of the Brigham and Women’s Hospital and Dana-Farber Cancer Institute, who was the discussant for the abstract, concluded. “I think this is a very exciting area, combining SBRT with immunotherapies.”