Introduction Availability/affordability and toxicity of PARP inhibitors (PARPi) for ovarian cancer treatment represent an unmet clinical need in LMICs, especially in women with anaemia/low-BMI. Through a CRUK/DBT-India-funded project, we generated proof-of-concept preclinical data showing durable parp inhibitory action after single dose rucaparib >72 hours. An academic/exploratory clinical feasibility study was planned for de-escalation/optimal scheduling, under GCIG mentorship (Sponsor: KolGOTRG).
Methods Institutional ethical approval was obtained. Patient-public-involvement workshops were held for assessing consumer preference/acceptance and willingness-to-pay. Platinum-sensitive (>3 months PFI) recurrent HGSC ovarian cancer patients were invited to participate, if deemed eligible for PARPi treatment. Bi-weekly rucaparib-generic (1200 mg, 2 days/week, 72hours apart) was administered orally for 12 weeks. Tolerability/toxicity/QOL and response-rate was assessed, followed by physician’s-choice of treatment/patients’-preference for continuation of intermittent regimen. PBMC was extracted and stored at 0/24/72/168 hours after the 1st rucaparib dose for future PK/PD studies. Barrier identification for implementing a dose de-escalation study was conducted using EASE model.
Results Of the 8 patients enrolled till April 2023, 3 women with large volume disease/ascites progressed at 12 weeks. 4 women continued till 24 weeks: 3 of them expressing willingness for continuing at 58, 52 and 48 weeks respectively due to favourable tolerability/QOL/response. No grade-3 haematological toxicity was recorded. Further 3 women on daily PARPi maintenance therapy, requiring dose de-escalation due to toxicity/affordability, opted for this regimen (outside study) and remain disease/toxicity free at >6 months.
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