The traditional six-month timeframe for defining platinum sensitivity is being challenged. A growing theory suggests that tumors progressing while on a PARP inhibitor have a distinct biology that responds poorly to subsequent platinum, indicating a potential need to move directly to therapies like ADCs.

The traditional practice of classifying recurrent ovarian cancer as 'platinum-sensitive' or 'platinum-resistant' based on a six-month treatment-free interval is rapidly becoming obsolete. The introduction of maintenance therapies like PARP inhibitors is changing tumor biology and response patterns, suggesting this simple time-based distinction no longer adequately reflects the clinical reality.

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.

While PARP inhibitors show some effect in all patients, clinical data revealed a significant survival advantage only in the HRD-positive subgroup. This has led to an FDA restriction, making biomarker testing a prerequisite for this class of drugs.

Seven-year follow-up from the SOLO-1 trial shows a profound, sustained overall survival benefit for upfront olaparib maintenance. This advantage was not nullified even though 44% of the placebo group later received a PARP inhibitor, highlighting a critical, irreplaceable window of opportunity.

Even patients with "low-risk" advanced ovarian cancer face an 85% chance of recurrence. This high baseline risk justifies aggressive upfront combination therapies, like adding bevacizumab, to maximize the potential for a curative outcome without leaving any options off the table.

While retreating with a PARP inhibitor after a long progression-free interval is a viable strategy for patients with BRCA mutations, experts express caution and hesitancy in applying the same approach to patients who are HRD-deficient but BRCA wild-type, partly due to changing FDA labels.

The initial broad enthusiasm for PARP inhibitors in ovarian cancer has been refined. New data confirms a lack of overall survival improvement for patients with HRD-negative (or HR proficient) tumors, pushing clinicians toward a precision medicine approach where these drugs are reserved for patients with BRCA mutations or HRD-positive disease who are most likely to benefit.