Prexasertib works in select patients with recurrent ovarian cancer

CHK1 inhibition with prexasertib appears to have durable activity in some patients with recurrent ovarian cancer regardless of clinical characteristics, BRCA status, or prior therapies, according to the results of a phase II trial.

The trial included 169 ovarian cancer patients (median age 59 years) who were grouped as follows: platinum resistant, BRCA-wildtype with ≥3 lines prior therapy (cohort 1, n=53); platinum resistant BRCA-wildtype with <3 lines prior therapy (cohort 2, n=46); platinum resistant, BRCA-mutated with prior PARP inhibitor therapy (cohort 3, n=41); platinum refractory, BRCA-mutated, or BRCA-wildtype with any number of prior therapy lines (cohort 4, n=29).

Most patients were diagnosed at stage III/IV (89.9 percent), with the median time from diagnosis being longer in cohorts 1 and 3 (1,554 and 1,803 days, respectively) than in cohorts 2 and 4 (526 and 446 days, respectively). All patients were administered 105-mg/m² intravenous infusion of prexasertib every 2 weeks (days 1 and 15) in a 4-week cycle, until radiographic disease progression, unacceptable toxicity, or patient/physician request to discontinue.

Doses administered were based on the patients’ body surface area at the beginning of each cycle. Dose reductions to 80 (first dose reduction) or 60 mg/m² (second dose reduction) were required for Grade 3/4 nonhematologic AEs and febrile neutropenia occurring with prophylactic GCSF.

The primary endpoint of objective response rates were 12.1 percent among platinum-resistant patients (cohorts 1-3) and 6.9 percent among platinum-refractory patients (cohort 4).

Disease control rates were 37.1 percent among platinum-resistant patients, being consistent across cohorts, and 31.0 percent among platinum refractory patients.

The safety profile of prexasertib was consistent with the drug’s mechanism of action. The most common treatment-related adverse events of all grades included thrombocytopenia, neutropenia, fatigue, nausea, and anaemia.