Stereotactic Radiotherapy and Short-course Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial.

backgroundStereotactic ablative body radiotherapy (SABR) is an option for oligometastatic clear cell renal cell carcinoma (ccRCC) but is limited by a lack of prospective clinical trial data.

objectiveThe RAPPORT trial evaluated the safety and efficacy of total metastatic irradiation followed by short-course anti-programmed death receptor-1 immunotherapy in patients with oligometastatic ccRCC. DESIGN SETTING, AND

participantsRAPPORT was a single-arm multi-institutional phase I/II trial (NCT02855203). Patients with two or fewer lines of prior systemic therapy and one to five oligometastases from ccRCC were eligible.

interventionA single fraction of 20 Gy SABR (or if not feasible, ten fractions of 3 Gy) was given to all metastatic sites, followed by pembrolizumab 200 mg administered Q3W for eight cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The endpoints were adverse events (AEs), disease control rate (DCR) for at least 6 mo, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The Kaplan-Meier method was used for time-to-event endpoints. Freedom from local progression (FFLP) was assessed per lesion adding patient as a cluster effect. RESULTS AND LIMITATIONS: Thirty evaluable patients, with a median age of 62 yr, were enrolled. The median follow-up was 28 mo. There were 44% of patients with intermediate-risk and 56% with favorable-risk disease. Eighty-three oligometastases were irradiated (median three per patient): eight adrenal, 11 bone, 43 lung, 12 lymph node, and nine soft tissue. Four patients (13%) had grade 3 treatment-related AEs: pneumonitis (n = 2), dyspnea (n = 1), and elevated alkaline phosphatase/alanine transaminase (n = 1). There were no grade 4 or 5 AEs. FFLP at 2 yr was 92%. ORR was 63% and DCR was 83%. Estimated 1- and 2-yr OS was 90% and 74%, respectively, and PFS was 60% and 45%, respectively. Limitations include a single-arm design and selected patient population.

conclusionsSABR and short-course pembrolizumab in oligometastatic ccRCC is well tolerated, with excellent local control. Durable responses and encouraging PFS were observed, warranting further investigation. PATIENT SUMMARY: The RAPPORT trial investigated the combination of high-dose precision radiotherapy and a short course of immunotherapy in patients with low-volume metastatic kidney cancer. We found that this treatment regimen was well tolerated, with excellent cancer control in sites of known disease. A proportion of patients were free from cancer relapse in the longer term, and these encouraging findings warrant further investigation.