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 definition of platinum-resistant ovarian cancer based on a six-month recurrence interval is becoming less rigid. Clinicians recognize this timeframe can be an arbitrary surrogate for tumor biology, influenced by imaging schedules. The paradigm is shifting, especially post-PARP inhibitor therapy, where the value of re-challenging with platinum is being reconsidered despite shorter intervals.

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.

Real-world data shows that in platinum-sensitive ovarian cancer patients who have progressed on PARP inhibitors, subsequent platinum-based chemotherapy has a surprisingly low response rate of only 20%. This quantifies a significant opportunity for highly active ADCs to potentially replace platinum in this growing patient population.

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.

The term "platinum-resistant" is being replaced by "platinum-ineligible" because the traditional 6-month relapse cutoff is an arbitrary and poor predictor of treatment response. The new term more accurately identifies patients who progress during or immediately after platinum therapy, acknowledging that others may still benefit.

For HRD-positive ovarian cancer, a strong initial response to platinum chemotherapy may justify using a PARP inhibitor alone for maintenance. A weaker response, however, suggests adding bevacizumab for a potentially greater benefit, using clinical response as a key decision-making tool.

When an HRD test is inconclusive due to insufficient tumor tissue after neoadjuvant chemotherapy, it can paradoxically indicate a very strong response to treatment and high platinum sensitivity, as there is little to no residual tumor to analyze.

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.