Data from DUO-E and RUBY Part 2 trials show adding a PARP inhibitor to chemo-immunotherapy provides only a small PFS benefit. Experts are not convinced of its value, citing a lack of overall survival benefit and potential for harm.

Experts are cautious about using ADCs as long-term frontline maintenance therapy in ovarian cancer. Unlike oral PARPs, prolonged administration of these potent chemotherapies could cause cumulative toxicities, especially bone marrow suppression, potentially rendering patients unable to tolerate essential treatments upon relapse.

The widespread use of PARP inhibitors has altered tumor biology in platinum-sensitive ovarian cancer. A recent meta-analysis of heavily pretreated patients, 97% of whom had prior PARP inhibitor exposure, revealed an objective response rate to subsequent therapy of only 17%—far lower than historical expectations, highlighting a critical unmet clinical need.

The selection between PARP inhibitors like olaparib and niraparib is not one-size-fits-all. It's a personalized decision based on patient preference for dosing frequency (once vs. twice daily), tolerance for side effects like hypertension, and potential drug-drug interactions.

To combat the significant myelosuppression from the standard 28-day venetoclax cycle in AML, many clinicians are adopting a strategy of performing a bone marrow biopsy around day 21 and pausing the drug if blast clearance is achieved to allow for hematologic recovery.

While these drugs can cause neutropenia, it rarely leads to infections. Patients often feel clinically well despite low neutrophil counts. This 'paper problem' can usually be managed with G-CSF without needing to dose-reduce the primary CLL therapy.

The development of PARP-1 selective inhibitors like seriparib signals a shift in drug innovation. Instead of only chasing higher efficacy, these new agents aim for a more favorable toxicity profile (less GI toxicity, fewer dose discontinuations) to improve patient quality of life and treatment adherence.

The risk of developing myeloid neoplasms from PARP inhibitors in the frontline ovarian cancer setting is very low, around 1%. However, it is critical to adhere to the recommended 2-3 year treatment duration and then stop the therapy to avoid unnecessary long-term risk.

While adding a menin inhibitor to the azacitidine/venetoclax doublet for older/unfit AML patients increases response rates, it leaves little reserve for marrow function. This can lead to increased risk of early, fatal complications like infection or bleeding, requiring careful dose management.