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A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer

Panagiotis A Konstantinopoulos1, Jung-Min Lee2, Bo Gao3

  • 1Dana-Farber Cancer Institute, Boston, MA, USA.

Gynecologic Oncology
|October 3, 2022
PubMed
Abstract

Insights

Prexasertib showed durable activity in recurrent ovarian cancer patients, regardless of BRCA status or prior treatments. Further research is needed to identify predictive biomarkers for optimal patient selection.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • High-grade serous ovarian cancer has a poor prognosis, especially in platinum-resistant or refractory cases.
  • Novel therapeutic strategies are crucial for overcoming treatment resistance in ovarian cancer.
  • CHK1 inhibition with prexasertib represents a potential new treatment avenue targeting cell cycle checkpoints.

Purpose of the Study:

  • To evaluate the efficacy and safety of prexasertib as a single agent in patients with recurrent ovarian cancer.
  • To assess the objective response rate (ORR) and disease control rate (DCR) in platinum-resistant and platinum-refractory ovarian cancer cohorts.
  • To explore potential biomarkers for identifying patient subsets who may benefit from prexasertib treatment.

Main Methods:

  • A Phase 2 multicenter trial (NCT03414047) enrolled 169 patients with ovarian cancer into four distinct cohorts based on platinum sensitivity, BRCA status, and prior therapy.
  • The primary endpoint was objective response rate (ORR), with secondary endpoints including disease control rate (DCR) and safety.
  • Tumor biopsy DNA was sequenced to identify potential predictive biomarkers for treatment response.

Main Results:

  • The ORR was 12.1% in platinum-resistant patients and 6.9% in platinum-refractory patients.
  • DCR was 37.1% in platinum-resistant patients and 31.0% in platinum-refractory patients, showing consistent activity across subgroups.
  • Common treatment-related adverse events included thrombocytopenia, neutropenia, fatigue, nausea, and anemia, consistent with prexasertib's mechanism of action.

Conclusions:

  • Prexasertib demonstrated durable single-agent activity in a subset of recurrent ovarian cancer patients, irrespective of clinical characteristics, BRCA status, or prior therapies (including PARPi).
  • No clear correlation was found between genomic alterations and treatment response, highlighting the need for novel biomarker discovery.
  • Alternative biomarker approaches are essential for accurately identifying patients most likely to respond to prexasertib.
Keywords:
Checkpoint kinase inhibitorOvarian cancerPlatinum refractoryPlatinum resistant

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