Stereotactic radiotherapy with pembrolizumab promising for oligometastatic kidney cancer

Reuters Health - 29/12/2021 - The combination of stereotactic ablative body radiotherapy (SABR) and a short-course of pembrolizumab is well tolerated and provides excellent local control of oligometastatic renal-cell carcinoma (RCC), according to results of the RAPPORT trial.

"Durable responses and encouraging" progression-free survival (PFS) were observed with this approach, warranting further investigation, report Dr. Shankar Siva of Peter MacCallum Cancer Center, in Melbourne, Australia, and colleagues in European Urology.

The RAPPORT trial was a multi-institutional, single-arm, phase-1/2 study testing safety and efficacy of SABR and pembrolizumab in 30 patients with two or fewer lines of prior systemic therapy and one to five oligometastases from clear-cell RCC. Forty-four percent of patients had intermediate-risk and 56% had favorable-risk disease.

All patients received a single fraction of 20 Gy SABR (or if not feasible, 10 fractions of 3 Gy) to all metastatic sites, followed by pembrolizumab 200 mg administered every three weeks for eight cycles.

Four patients (13%) had one or more grade-3 treatment-related adverse events, including pneumonitis in two, dyspnea in one and elevated alkaline phosphatase/alanine transaminase in one. There were no grade 4 or 5 adverse events.

At two years, freedom from local progression was 92%, the disease control rate was 83% and the objective response rate was 63%. Estimated one-year and two-year overall survival rate was 90% and 74%, respectively, and PFS was 60% and 45%, respectively.

"Taken together, these results show that total metastatic ablation with SABR in combination with pembrolizumab was safe and locally effective, and has durable antitumor activity in patients with oligometastatic ccRCC," Dr. Siva and colleagues conclude.

Limitations of the study include the single-arm design and the small number of highly selected patients with low-volume oligometastatic disease, non-poor-risk cases, and without liver metastases. It was also a relatively treatment-naive population with only 30% having prior metastasectomy.

"We propose that future areas of research could focus on the role of adding total metastatic ablation to doublet therapy in patients with synchronous intermediate- or poor-risk ccRCC to improve outcomes. Biomarkers of response and long-term disease control would be important to evaluate in order to identify patients who would derive benefit," they write.

"For favorable-risk oligometastatic disease, future research could address whether SABR and short-course immunotherapy combinations can provide more durable control than metastasis-directed therapy alone," they add.

SOURCE: https://bit.ly/3FCbFOe European Urology, online December 23, 2021.

By Reuters Staff



Posted on 29 December 202112 January 2022