In ovarian cancer trials, many patients in the placebo group later receive a PARP inhibitor. This crossover "pollutes" the data, making it difficult to prove a statistically significant overall survival benefit for frontline PARP maintenance, despite its clear effectiveness.
Prolonged PARP inhibitor use, especially beyond two years in BRCA-mutated patients, significantly increases the risk of secondary malignancies like MDS/AML. The baseline risk in this population is already elevated, and PARP inhibitors exacerbate it.
The growing evidence of increased long-term MDS/AML risk with PARP inhibitors provides a compelling clinical reason to stop maintenance therapy at the two-year mark, even for patients who are stable and hesitant to discontinue treatment.
A strong response to neoadjuvant chemotherapy can eliminate viable tumor cells, making subsequent HRD testing impossible. It is critical to obtain an adequate biopsy for molecular testing before initiating systemic therapy to guide future maintenance decisions.
Clinicians should view HRD scores as a spectrum rather than a simple positive/negative result. For a patient with a score near the arbitrary cutoff and an excellent clinical response to platinum, oncologists may advocate for insurance coverage of PARP inhibitors.
For ovarian cancer patients experiencing significant ocular side effects from the ADC mervituximab, switching the dosing schedule from every three weeks to every four weeks can resolve the toxicity by allowing an extra week for recovery.
The onset of ocular symptoms from mervituximab is highly predictable, almost always starting between days 10 and 14 of the second treatment cycle. Proactively warning patients about this specific timeline can reduce their anxiety if and when symptoms appear.
The decision between new regimens in platinum-resistant ovarian cancer—relicorolant/nab-paclitaxel vs. pembrolizumab/paclitaxel—hinges on the patient's need for bevacizumab. If bevacizumab is required for symptomatic disease, the relicorolant combination is off the table.
A surprising trend in ovarian cancer is the consistent efficacy of antibody-drug conjugates (ADCs) with a TOPA1 payload. Regardless of the specific cell surface target, these agents are achieving response rates around 50%, suggesting the payload's potency is the primary driver.