Avelumab combined with stereotactic ablative body radiotherapy in metastatic castration-resistant prostate cancer: The phase 2 ICE-PAC clinical trial

Kwan, EM; Spain, L; Anton, A; Gan, CL; Garrett, L; Chang, D; Liow, E; Bennett, C; Zheng, T; Yu, J; Dai, C; Du, P; Jia, S; Fettke, H; Abou-Seif, C; Kothari, G; Shaw, M; Parente, P; Pezaro, C; Tran, B; Siva, S; Azad, AA

Author(s): Kwan, EM; Spain, L; Anton, A; Gan, CL; Garrett, L; Chang, D; Liow, E; Bennett, C; Zheng, T; Yu, J; Dai, C; Du, P; Jia, S; Fettke, H; Abou-Seif, C; Kothari, G; Shaw, M; Parente, P; Pezaro, C; Tran, B; Siva, S; Azad, AA;
Details: Publication Year 2022,Volume 81,Issue #3,Page 253-262
Journal Title: European Urology
Abstract: BACKGROUND: Immune checkpoint inhibitor monotherapy in metastatic castration-resistant prostate cancer (mCRPC) has produced modest results. High-dose radiotherapy may be synergistic with checkpoint inhibitors. OBJECTIVE: To evaluate the efficacy and safety of the PD-L1 inhibitor avelumab with stereotactic ablative body radiotherapy (SABR) in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to July 2019, this prospective phase 2 study enrolled 31 men with progressive mCRPC after at least one prior androgen receptor-directed therapy. Median follow-up was 18.0 mo. INTERVENTION: Avelumab 10 mg/kg intravenously every 2 wk for 24 wk (12 cycles). A single fraction of SABR (20 Gy) was administered to one or two disease sites within 5 d before the first and second avelumab treatments. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the disease control rate (DCR), defined as a confirmed complete or partial response of any duration, or stable disease/non-complete response/non-progressive disease for ≥6 mo (Prostate Cancer Clinical Trials Working Group 3-modified Response Evaluation Criteria in Solid Tumours version 1.1). Secondary endpoints were the objective response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS), and safety. DCR and ORR were calculated using the Clopper-Pearson exact binomial method. RESULTS AND LIMITATIONS: Thirty-one evaluable men were enrolled (median age 71 yr, 71% with ≥2 prior mCRPC therapy lines, 81% with >5 total metastases). The DCR was 48% (15/31; 95% confidence interval [CI] 30-67%) and ORR was 31% (five of 16; 95% CI 11-59%). The ORR in nonirradiated lesions was 33% (four of 12; 95% CI 10-65%). Median rPFS was 8.4 mo (95% CI 4.5-not reached [NR]) and median OS was 14.1 mo (95% CI 8.9-NR). Grade 3-4 treatment-related adverse events occurred in six patients (16%), with three (10%) requiring high-dose corticosteroid therapy. Plasma androgen receptor alterations were associated with lower DCR (22% vs 71%, p = 0.13; Fisher's exact test). Limitations include the small sample size and the absence of a control arm. CONCLUSIONS: Avelumab with SABR demonstrated encouraging activity and acceptable toxicity in treatment-refractory mCRPC. This combination warrants further investigation. PATIENT SUMMARY: In this study of men with advanced and heavily pretreated prostate cancer, combining stereotactic radiotherapy with avelumab immunotherapy was safe and resulted in nearly half of patients experiencing cancer control for 6 months or longer. Stereotactic radiotherapy may potentially improve the effectiveness of immunotherapy in prostate cancer.
Keywords: Castration-resistant; Checkpoint inhibitor; Immunotherapy; Metastasis-directed therapy; Prostate cancer; Stereotactic ablative body radiotherapy; Stereotactic body radiation therapy
Research Division(s): Personalised Oncology
PubMed ID: 34493414
Publisher's Version: https://doi.org/10.1016/j.eururo.2021.08.011
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-09-17 11:23:15

Last Modified: 2022-04-20 12:10:30