Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk


The cover for issue 30 of Oncotarget features Figure 3, "Waterfall plot (A) and duration on the study (B)," by Lampert, et al."

To investigate maximum tolerated dose, activity and predictive biomarkers of olaparib with carboplatin in BRCA wild-type high grade serous ovarian carcinoma patients a 3+3 dose escalation study examined olaparib capsules with carboplatin every 21 days for 8 cycles, followed by olaparib 400 mg BID maintenance.

MTD was olaparib 400 mg BID + carboplatin AUC4.

Dr. Jung-Min Lee from the Women's Malignancies Branch, Center for Cancer Research, at the National Cancer Institute, in Bethesda, MD, USA said "High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in the United States (U.S.), with an overall 5-year survival rate under 40%"

Figure 1: Study Schema

In preclinical studies, PARP inhibitors showed enhanced cytotoxicity in both HGSOC with BRCA mutations and HRR-deficient HGSOC with wild-type BRCA, suggesting a broad applicability of PARPi in clinic.

Olaparib is the first approved PARPi for use as monotherapy in gBRCAm patients with recurrent HGSOC who had >3 prior treatment regimens.

It is also FDA-approved as a maintenance therapy in platinum-sensitive recurrent HGSOC patients regardless of their BRCA status, as well as for frontline maintenance in BRCAm patients.

Like olaparib and rucaparib, niraparib is approved as a maintenance therapy in platinum-sensitive recurrent HGSOC patients who achieved response following chemotherapy.

The Lee Research team concluded, "There are now a number of PARPi combination studies in phase I to III clinical trials in ovarian cancer, though primarily focusing on the platinum-sensitive and BRCAm population."

Full text - https://doi.org/10.18632/oncotarget.26869

Correspondence to - Jung-Min Lee- [email protected]

Keywords - high-grade serous ovarian cancer, BRCA wild type, olaparib, carboplatin

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