Targeted composite value-based endpoints in platinum-sensitive recurrent ovarian cancer

Area of Science:

• Oncology
• Clinical Pharmacology
• Biostatistics

Background:

• Platinum-sensitive recurrent ovarian cancer (PSROC) has limited treatment options, with bevacizumab and PARP inhibitors (PARPi) being FDA-approved.
• Clinical decisions for PSROC therapies require careful consideration before initiating chemotherapy.

Purpose of the Study:

• To assess the relative value of concurrent and maintenance biologic therapies for PSROC using established value frameworks.
• To construct personalized value scorecards for patients based on their specific genetic profiles (BRCA mutations, HRD, wild-type BRCA).

Main Methods:

• Value scores were calculated for bevacizumab, olaparib, niraparib, and rucaparib based on data from pivotal randomized controlled trials.
• The American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks were employed.
• Scorecards were personalized for patients with germline/somatic-BRCA mutations, homologous recombination deficiency (HRD), and wild-type BRCA (wBRCA).

Main Results:

• Maintenance PARPi demonstrated the highest ASCO value scores in germline/somatic-BRCA mutated cohorts (e.g., olaparib up to 62).
• HRD cohorts showed moderately lower scores, while wild-type BRCA (wBRCA) cohorts and bevacizumab yielded the lowest scores.
• ESMO scores corroborated these findings, indicating high value for PARPi in BRCA-mutated cohorts and low value in wBRCA cohorts.

Conclusions:

• The therapeutic value of maintenance PARPi in PSROC is significantly influenced by BRCA mutation status.
• Highest value is observed in patients with germline or somatic BRCA mutations.
• Personalized value scorecards serve as a crucial tool for evaluating the harm-benefit profile of maintenance PARPi in PSROC.