BMS-986365 Cannot Be Combined with PARP Inhibitors Based on Current Evidence
I cannot recommend combining BMS-986365 with PARP inhibitors because there is no available evidence regarding BMS-986365 in the provided literature or established medical databases. The drug name BMS-986365 does not appear in any of the guideline documents, FDA approvals, or clinical trials provided.
What the Evidence Actually Shows
The evidence provided exclusively addresses FDA-approved PARP inhibitor combinations with androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer, not BMS-986365:
Established PARP Inhibitor Combinations
Three PARP inhibitor combinations are FDA-approved and supported by NCCN guidelines for mCRPC:
Olaparib + Abiraterone: FDA-approved May 2023 for BRCA1/2 mutation-positive mCRPC, with Category 1 recommendation for treatment-naïve patients without prior docetaxel or novel hormone therapy 1
Talazoparib + Enzalutamide: FDA-approved June 2023 for HRR gene mutations (BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), with Category 1 recommendation for treatment-naïve mCRPC 1
Niraparib + Abiraterone: FDA-approved August 2023 for BRCA1/2 mutation-positive mCRPC, with Category 1 recommendation for treatment-naïve patients 1
Mechanism Supporting These Combinations
PARP inhibitors are specifically combined with androgen receptor pathway inhibitors based on biological rationale:
- Androgen receptor inhibitors downregulate DNA repair genes, creating synthetic lethality when combined with PARP inhibition 1
- This synergistic effect improves radiographic progression-free survival even in patients without HRR mutations 1, 2, 3
Critical Knowledge Gap
Without knowing what BMS-986365 is—its mechanism of action, drug class, or therapeutic target—no evidence-based recommendation can be made regarding combination with PARP inhibitors. The safety profile, drug-drug interactions, and potential for overlapping toxicities (particularly hematologic adverse events like anemia, thrombocytopenia, and neutropenia that are common with PARP inhibitors) cannot be assessed 1.
Common PARP Inhibitor Toxicities to Consider
If BMS-986365 were to be combined with any PARP inhibitor, the following toxicity profile would need careful monitoring:
- Hematologic toxicities: Anemia (21-33% grade ≥3), thrombocytopenia, neutropenia 1, 2
- Dose interruptions: Required in 75% of patients receiving talazoparib combinations 1
- Dose reductions: Needed in 56% of patients due to adverse events 1
To answer this question appropriately, you must first identify what BMS-986365 is, then search for specific drug interaction data, clinical trials, or mechanistic rationale supporting or contraindicating combination with PARP inhibitors.