Real-world data of PARP inhibitors in first-line maintenance for BRCA-mutated or HRD-positive advanced ovarian cancer: a multicentre retrospective study from India.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as a significant advancement in the maintenance treatment of advanced High-Grade Serous Ovarian Cancer (HGSOC), particularly in patients with BRCA mutations or Homologous Recombination Deficiency (HRD). While randomized trials have demonstrated their efficacy, real-world evidence from low- and middle-income countries (LMIC) like India remains scarce. This retrospective observational multicentre study aimed to assess the safety and effectiveness of first-line maintenance therapy with Olaparib or Rucaparib in Indian patients with BRCA-mutated (BRCAmut) or HRD-positive (HRD+) advanced HGSOC. RESULTS: The study evaluated data from 46 patients treated between May 2019 and December 2022 across six oncology centres under the BIRAC-supported Network of Oncology Clinical Trials of India. The median age was 50.5 years, with all having HGS histopathology. Stage III disease was present in 32(69.6%), and 12(26.1%) had a family history of cancer. Median turnaround time for gBRCA and HRD investigation was 18 and 20.5 days, respectively. BRCA1mut were seen in 30(65.2%), BRCA2 in 5(10.9%), and non-BRCA HRD + in 11(23.9%). Olaparib was given to 27(58.7%) and Rucaparib to 19(41.3%). At a median follow-up of 22.5 months (range 18–53), the median PFS was not reached. The 12 and 18-month PFS rates were 97.8% and 86.9%, respectively. No significant difference in mPFS was found between the two drugs or between BRCAmut and BRCA-wild HRD+ patients (NR vs. 29 months, p = 0.219) groups. Dose reductions were made in 18(39.1%) of patients due to toxicity [N = 9(50%)] or cost [N = 9(50%)], with no observed impact on PFS between the standard dose and the reduced dose. The major prevalent grade ≥ 3 toxicities comprised anaemia (13%), fatigue (6.5%), and thrombocytopenia (2.2%). CONCLUSION: Despite limitations of a retrospective design, this study supports the clinical efficacy and tolerability of PARPi in LMIC, with efficacy and toxicity outcomes comparable to global trial data. There were no statistically significant differences observed between Olaparib and Rucaparib, standard and reduced doses, or BRCAmut and HRD+ patients. This study supports the feasibility of incorporating PARPi into frontline maintenance therapy for advanced HGSOC in resource-limited environments.