Ceralasertib Olaparib Combo Elicits Promising Activity In Parp Resistant Ovarian Cancer

July 15, 2021 2:43 pm

The following article is provided by The Clearity Foundation to support women with ovarian cancer and their families. Learn more about The Clearity Foundation and the services we provide directly to women as they make treatment decisions and navigate emotional impacts of their diagnosis.

platinum-sensitive

The combination of ceralasertib and olaparib induced clinical activity and was well tolerated in patients with homologous recombination deficient, recurrent platinum-sensitive, PARP inhibitor–resistant ovarian cancer.

The combination of ceralasertib and olaparib (Lynparza) induced clinical activity and was well tolerated in patients with homologous recombination deficient (HRD), recurrent platinum-sensitive, PARP inhibitor–resistant ovarian cancer, according to findings from the phase 2 CAPRI trial (NCT03462342) that were presented during the 2021 ASCO Annual Meeting.1

In the trial, patients received 300 mg of oral olaparib twice daily on days 1 through 28 plus 160 mg of oral ceralasertib daily on days 1 through 7. Among 13 evaluable patients, the objective response rate (ORR) was 46% (n = 6), and the progression-free survival was 7.5 months (95% CI, 4.7–not reached).

Stephanie Lorene Wethington, MD, MSc
Stephanie Lorene Wethington, MD, MSc

Among patients with germline BRCA mutations, somatic BRCA mutations, and HRD positivity, the ORRs were 69% (n = 9), 23% (n = 3), and 8% (n = 1), respectively.

Patients who had received a prior PARP inhibitor in the frontline maintenance, second-line maintenance, and treatment settings had ORRs of 8% (n = 1), 38% (n = 5), and 54% (n = 7), respectively.

Grade 3 or 4 adverse effects included anemia (7.7%; n = 1), thrombocytopenia (23.1%; n = 3), leukopenia (7.7%; n = 1), and neutropenia (7.7%; n = 1). Investigators reported 2 treatment interruptions because of thrombocytopenia and COVID-19 infection, and 4 dose reductions because of olaparib (n = 3) and ceralasertib (n = 1).

“In the recurrent setting, we really want to be sure that we are providing our patients with regimens that are well tolerated. In this small series, we saw excellent tolerance and a very intriguing response rate. This by no means is a definitive series, but [this] well-tolerated regimen with a favorable response rate is worthy of further investigation,” said lead study author, Stephanie Lorene Wethington, MD, MSc.

In an interview with OncLive, Wethington, director of The Susan L. Burgert MD Gynecologic Oncology Survivorship Program and an assistant professor of Gynecology and Obstetrics at Johns Hopkins Medicine, discussed the results of the study and importance of studying combination treatments in patients with PARP-resistant ovarian cancer.

This article was published by OncLive.

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