Tissue may become insufficient or necrotic after neoadjuvant chemotherapy, leading to failed molecular tests. Securing tissue for comprehensive biomarker analysis at the initial diagnosis is crucial to guide treatment decisions, including PARP inhibitor eligibility.
Retrospective data from the PAOLA-one trial shows a significant reduction in benefit from subsequent platinum-based therapy for patients who progressed while on a PARP inhibitor. Objective response rates dropped from 50-60% (placebo group) to 30% (PARP group).
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.
If multiple attempts at HRD biomarker testing are indeterminate, a strong clinical response to platinum-based neoadjuvant chemotherapy can serve as a surrogate for HRD positivity. This clinical observation can support the decision to treat the patient as HRD-positive and offer a PARP inhibitor.
Early clinical trial data for the ADC mirvetuximab shows a response rate of 39% in patients with one to three prior lines of therapy. This rate drops significantly for patients with four or more lines, supporting prioritization of this drug earlier in the platinum-resistant setting.
Concordance between local and central HER2 testing for ovarian cancer is poor. However, early data suggests the T-DXd antibody-drug conjugate is effective regardless of this variability, meaning any positive signal could be clinically actionable for this difficult-to-treat cancer.
Despite concerns about cross-resistance from breast cancer data, experts would consider sequencing ADCs with the same payload (e.g., deruxtecan). The rationale is that even a diminished response rate (e.g., 30%) is still significantly better than the 15% seen with standard single-agent cytotoxics.
The persistent separation of survival curves in the ROSELLA trial suggests relacorilant's benefit extends beyond sensitizing tumors to chemotherapy. By acting as a glucocorticoid receptor antagonist and blocking immunosuppressive cortisol, it may also have a favorable immune-modulatory effect.
The efficacy of relacorilant, a glucocorticoid antagonist, has raised concerns that routine steroid use with chemotherapy may induce resistance. This has led clinicians to reduce steroid doses, questioning a long-standing practice and its potential to blunt the therapeutic effects of chemotherapy.
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.