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ESMO 2019: ATR Inhibitor Plus Gemcitabine in High-Grade Serous Ovarian Cancer

By: Lauren Harrison, MS
Posted: Monday, October 21, 2019

A combination of gemcitabine plus the selective ATR inhibitor M6620 appears to be superior to gemcitabine alone—and without an increase in toxicity—in patients with high-grade serous ovarian carcinoma. However, more research is needed to fully evaluate this drug combination. This study was presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona by Panagiotis A. Konstantinopoulos, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues (Abstract LBA60).

This phase II multicenter, open-label trial enrolled 70 patients. All patients had platinum-resistant high-grade serous ovarian carcinoma and were randomly assigned to receive either gemcitabine or gemcitabine plus M6620 in a 21-day cycle. Gemcitabine was administered intravenously (IV) in 1,000-mg/m2 doses on days 1 and 8 in both groups, followed by 210 mg/m2 IV of M6620 on days 2 and 9 in the combination group. Treatment was continued until disease progression or intolerable toxicity. Patients who received gemcitabine alone were allowed to switch to gemcitabine plus M6620 upon disease progression.

In total, 36 patients received gemcitabine and 34 were treated with the combination protocol. The progression-free survival was estimated to be 14.7 weeks with gemcitabine and 22.9 weeks with gemcitabine/M6620 (hazard ratio = 0.57). Patients who seemed to benefit the most from the addition of M6620 were those who were stratified into the platinum-free interval of up to 3 months (hazard ratio = 0.31). There was no significant difference seen between the two groups for patients with a platinum-free interval longer than 3 months. It is important to note that there was no increase in the treatment-related side effects in the group receiving gemcitabine plus M6620.

Disclosure: For full disclosures of the study authors, visit esmo.org.



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