Impact of BRCA status in patients with castrate-resistant prostate cancer undergoing abiraterone +/- stereotactic body radiotherapy: ARTO trial.

Abstract

397 Background: ARTO (NCT03449719) was a multicenter randomized phase II trial exploring the benefit of concomitant Abiraterone acetate and stereotactic body radiotherapy (SBRT) administration in oligometastatic castrate resistant prostate cancer patients (omCRPC). Both biochemical response and biochemical progression free survival (bPFS) were improved by the addition of SBRT in the experimental arm if compared to abiraterone alone. Here is presented a secondary analysis focusing on prognostic impact of BRCA alterations in enrolled patients. Methods: Patients affected by omCRPC (< 3 non-visceral metastatic lesions) were randomized 1:1 to receive either Abiraterone alone (ARM A) or associated with concomitant SBRT on all sites of disease (ARM B). Subgroup analysis focusing on BRCA positive, negative or BRCA untested patients were conducted. Results: Overall population consisted of 157 patients, 89 patients were tested for BRCA 1 and BRCA 2 alterations, of whom 80 and 9 patients resulted negative and positive, respectively. Sixty eight patients were untested. In the BRCA negative population, bPFS events were registered in 43 patients (72.1 and 32.4% of population included in ARM A and B, respectively). Six bPFS events were registered in BRCA positive population (80 and 50% of patients included in ARM A and B, respectively). In the BRCA untested population, 26 bPFS events were detected (52.9 and 23.5% of patients included in ARM A and B, respectively). No significant difference in terms of bPFS was detected between BRCA positive and negative patients (HR 0.93, p=0.86). Conversely, BRCA untested patients had a significant lower risk of biochemical progression (HR 0.58, p=0.02). Benefit of SBRT in the experimental arm was confirmed both in the BRCA negative and BRCA untested populations in terms of bPFS, with HR of 0.37 (95% CI 0.19-0.73) and 0.50 (95% CI 0.14-0.76), respectively. In BRCA positive patients, results were inconclusive due to limited sample size (HR 0.5, 95% CI 0.09-2.89). Conclusions: In a well selected cohort of omCRPC included in a prospective trial, benefit of SBRT was confirmed in BRCA negative and untested patients. Larger cohorts of BRCA positive omCRPC patients undergoing SBRT are needed to confirm these results in this scenario. Clinical trial information: NCT03449719 . Biochemical progression free survival (BPFS) results in the two trial arms according to BRCA status. BRCA negative BRCA positive(vs negative) BRCA untested(vs negative) N Events N Events HR (95%CI), p N Events HR (95%CI), p BPFS 80 43 9 6 0,93(0,39-2,19)p=0,863 68 26 0,58(0,35-0,94)p=0,028 arm A 43 31 5 4 0,86(0,30-2,44)p=0,773 34 18 1,07(0,24-4,85)p=0,926 arm B 37 12 4 2 0,64(0,36-1,15)p=0,135 34 8 0,56(0,23-1,38)p=0,207