A phase II clinical trial provides the first evidence of a relatively high response rate in patients with low-grade serous ovarian cancer receiving the drug selumetinib. In the first targeted therapy clinical trial for low-grade serous ovarian cancer, 8 of 52 patients (15%) had a complete or objective partial response (tumor shrinkage) and 34 (65%) had no disease progression during the 2-year course of the study.

“These are remarkably encouraging results for what can ultimately be a devastating disease,” said David Gershenson, MD, professor in The University of Texas M.D. Anderson Cancer Center, Department of Gynecological Oncology and Reproductive Medicine.

Response rates for treatment for low-grade serous ovarian cancer are measured in single digits. This disease makes up 10% of ovarian cancer cases, and the cancer recurs or persists in 80% to 85% of these patients. These patients have a median overall survival of 80 months, about twice as long as those with high-grade disease, who are typically in their 60s at diagnosis and comprise 90% of patients with ovarian cancer. The average age of women with low-grade cancer falls in the early 40s; however, finding the disease in women in their 20s, 30s, and 40s and the occasional teenager is not uncommon.

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All 52 patients in this study had received at least one previous therapy, with 30 having had three or more. The clinical trial results with selumetinib included a median progression-free survival of 11 months. The disease did not worsen for at least 6 months for 34 patients (65%). The 2-year overall survival was 55%, while the median overall survival had not been reached, as more than half (61%) of the patients remained alive at the time of data cutoff for the study. No treatment-related deaths occurred. The study results were published in The Lancet Oncology (2012;14[2]:134-140).

The side effects ranged from cardiac and gastrointestinal toxicity to pain, fatigue, anemia, and dermatologic effects. Of the 52 patients, 22 had their doses reduced and 13 ultimately left the study due to side effects.

Researchers obtained tumor samples sufficient for DNA analysis from 34 patients. While 14 patients had KRAS mutations and two had BRAF mutations, there was no connection between having those mutations and whether the patients responded to selumetinib.

Gershenson said researchers will further explore the question of matching drug to mutation during a larger phase II/III clinical trial that he will lead with investigators from the NCI Gynecological Oncology Group and the United Kingdom. The study will enroll 250 patients and is likely to begin later this summer.

Phase II trials generally do not include a control or comparison group, but the team noted treatment results for 58 women not in the trial who were treated at M.D. Anderson with current options. Between them, these patients received 108 different chemotherapy regimens, which produced one complete and three partial responses for an overall response rate of 3.7%.