1619P - Efficacy of carboplatin in patients with metastatic castration-resistant prostate cancer: Results from the biomarker-driven, randomised, outcome-adaptive ProBio trial

Background

Limited randomised data in metastatic castration-resistant prostate cancer (mCRPC) have demonstrated moderate effects of platinum-based chemotherapy. Retrospective analyses have suggested DNA repair deficiency (DRD) to be associated with improved platinum responses and survival outcomes. We compared the efficacy of carboplatin to physician’s choice of standard-of-care (SOC) in patients with mCRPC in the Prostate Biomarker (ProBio) trial platform.

Methods

Patients with mCRPC underwent circulating tumour DNA analysis before randomization. Men with either DRD or TP53 mutation were assigned to the investigational carboplatin or SOC control arm. Here, we compared progression-free survival (PFS) (evaluated by no longer clinically benefiting per PCWG3 criteria) as primary endpoint, and overall survival (OS).

Results

In total, 115 men were randomised, i.e. 72 to SOC and 43 to carboplatin, whereof 104/115 (90%) patients were initiating first or second line systemic therapy for mCRPC. Clinical characteristics and treatment history were similar between groups. A TP53 mutation was found in 24/43 (56%) carboplatin- and 39/72 (54%) SOC-treated patients. In the carboplatin arm 17/43 (40%) patients had DRD, with 8/43 (19%) being BRCA1/2-altered. In the SOC arm, DRD was detected in 16/72 (22%) patients, with 8/72 (11%) being BRCA1/2-altered. Carboplatin reached the prespecified threshold of futility. The Survival Time Ratio (STR) for PFS for carboplatin was 0.65 (90% credible Intervals (CI) 0.51, 0.82) compared with SOC, resulting in a median estimated PFS of 4.4 months (90% CI, 3.7, 5.3) for carboplatin versus 6.8 months (90% CI, 6.0, 7.9) for SOC arm. PFS for carboplatin remained inferior in DRD (STR 0.68, 90% CI 0.45-1.07) and TP53-altered (STR 0.76, 90% CI 0.57-1.05) subgroup analyses. The median estimated OS was 17.2 months (90% CI, 14.6-21.3) for carboplatin compared with 19.3 (90% CI, 16.8-23.2) for SOC.

Conclusions

Carboplatin is not favourable as compared to SOC in patients with mCRPC harboring DRD/TP53 mutations.

Clinical trial identification

NCT03903835, EudraCT 2018-002350-78.

Editorial acknowledgement

Legal entity responsible for the study

Karolinska Institutet.

Funding

Janssen Pharmaceuticals, AstraZeneca (Swedish Research Council, Swedish Cancer Society, Kom op tegen Kanker).

Disclosure

All authors have declared no conflicts of interest.