TRITON2 Supports Rucaparib For BRCA1/2-Mutated Metastatic CRPC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Metastatic castration-resistant prostate cancer (mCRPC) patients with a BRCA1 or BRCA2 mutation may benefit from the PARP inhibitor rucaparib, trial findings suggest.  

“Altogether, results from the TRITON2 study demonstrate that rucaparib has meaningful antitumor activity and a manageable safety profile in patients with mCRPC, as well as a deleterious germline or somatic BRCA alteration”, the researchers report in the Journal of Clinical Oncology. 

Overall, 115 patients with disease progression after up to two lines of next-generation androgen receptor (AR)-directed therapy and one taxane-based chemotherapy regimen received at least one dose of rucaparib 600 mg twice daily, explain lead investigator Wassim Abida, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-workers. 

The patients continued treatment for a median 8.1 months and were followed-up for a median 17.1 months, with 25.2% of patients continuing with rucaparib at the time of reporting. 

The objective response rate (ORR) was 43.5% for 62 patients assessed by a blinded independent radiology review and 50.8% for 65 patients assessed by the investigators directly.  

And the ORRs were comparable for the 44 patients with a germline and the 71 patients with a somatic BRCA mutation (42.9 vs 43.9%) as well as for those with a BRCA1 or BRCA2 mutation (33.3 vs 45.3%). 

However, “some differences were observed with PSA [prostate-specific antigen] response rates”, the researchers note. 

More than half (54.8%) of the 115 patients achieved a PSA response and this rate was higher among the 36 patients with biallelic alterations and the 21 patients with homozygous loss than the overall population, at 75.0% and 81.0%, respectively.  

Median radiographic progression-free survival was 9 months by blinded assessment and the 12-month overall survival was estimated to be 73.0%, albeit the data were yet to mature. 

Safety analysis indicated grade 3 and more severe treatment-emergent adverse events (TEAEs) occurred in 60.9% of patients, most commonly anaemia or low haemoglobin (25.2%), with 27.8% of patients requiring at least one packed red blood cell transfusion. 

In all, 56.5% of patients required a treatment interruption and 40.9% a dose reduction because of TEAEs, and 7.8% discontinued rucaparib for this reason. There were three deaths related to TEAEs, of which one case of acute respiratory distress syndrome was considered by the investigators to be related to rucaparib. 

Looking to the future, Wassim Abida and team say the phase III TRITON3 trial will continue to assess clinical benefit of rucaparib in mCRPC patients with a BRCA or ATM mutation, focusing on those who have received only one AR-directed therapy and no prior chemotherapy. 

“Rucaparib is being compared with physician’s choice of next-generation AR-directed therapy or docetaxel and will provide additional evidence of the effects of rucaparib treatment in men with mCRPC”, they explain. 

Reference  

Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol; Advance online publication 14 August 2020. doi: 10.1200/JCO.20.01035.