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Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial.
Kwan, Edmond M; Spain, Lavinia; Anton, Angelyn; Gan, Chun L; Garrett, Linda; Chang, Deborah; Liow, Elizabeth; Bennett, Caitlin; Zheng, Tiantian; Yu, Jianjun; Dai, Chao; Du, Pan; Jia, Shidong; Fettke, Heidi; Abou-Seif, Claire; Kothari, Gargi; Shaw, Mark; Parente, Phillip; Pezaro, Carmel; Tran, Ben; Siva, Shankar; Azad, Arun A.
Afiliación
  • Kwan EM; Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia; Department of Medical Oncology, Monash Health, Melbourne, Australia.
  • Spain L; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia.
  • Anton A; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
  • Gan CL; Department of Medical Oncology, Monash Health, Melbourne, Australia.
  • Garrett L; Department of Medical Oncology, Monash Health, Melbourne, Australia.
  • Chang D; Department of Medical Oncology, Monash Health, Melbourne, Australia.
  • Liow E; Department of Medical Oncology, Monash Health, Melbourne, Australia.
  • Bennett C; Eastern Health Clinical School, Monash University, Melbourne, Australia.
  • Zheng T; Predicine Inc., Hayward, CA, USA.
  • Yu J; Predicine Inc., Hayward, CA, USA.
  • Dai C; Predicine Inc., Hayward, CA, USA.
  • Du P; Predicine Inc., Hayward, CA, USA.
  • Jia S; Predicine Inc., Hayward, CA, USA.
  • Fettke H; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
  • Abou-Seif C; Department of Anatomical Pathology, Monash Health, Melbourne, Australia.
  • Kothari G; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Shaw M; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Parente P; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia.
  • Pezaro C; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia.
  • Tran B; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
  • Siva S; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Azad AA; Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: arun.azad@
Eur Urol ; 81(3): 253-262, 2022 Mar.
Article en En | MEDLINE | ID: mdl-34493414
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Eur Urol Año: 2022 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: Eur Urol Año: 2022 Tipo del documento: Article País de afiliación: Australia