The treatment landscape for platinum-resistant ovarian cancer has rapidly evolved into a biomarker-driven paradigm. Clinicians must now test for and choose between therapies targeting distinct markers like folate receptor alpha (mirvetuximab), HER2 (T-DXd), and PD-L1 (pembrolizumab), requiring a sophisticated sequencing strategy.

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.

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 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.

After a decade with no new therapies improving survival, the landscape for platinum-resistant ovarian cancer is transforming. The recent successes of mirvetuximab, the pembrolizumab/paclitaxel combo, and relacorilant/nab-paclitaxel have all demonstrated statistically significant overall survival benefits, heralding a new era of effective options.

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.

The clinical lexicon for recurrent ovarian cancer is evolving. The term "platinum resistant" is being replaced by "platinum ineligible." This reflects a more nuanced clinical judgment that platinum-based chemotherapy is not the best option for a patient's recurrence, rather than being based solely on a time-defined interval of relapse.