Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial.
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, ANDPARTICIPANTS:
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 STATISTICALANALYSIS:
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 ANDLIMITATIONS:
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. PATIENTSUMMARY:
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.Palabras clave
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