Research in Advanced Ovarian Cancer Shows Promise

By Ursula Matulonis, MD

After a long period of slow progress, new knowledge about the genetics of ovarian cancer is leading to the development and testing of new therapies.

Researchers at the Susan F. Smith Center for Women’s Cancers will soon be launching several phase 3 clinical trials testing drugs known as PARP inhibitors for patients with platinum-sensitive recurrent ovarian cancer – tumors that initially responded to platinum-based chemotherapy agents but have shown evidence of regrowth at least six months after treatment. Phase 3 trials test drugs in large numbers of patients to evaluate the drugs’ effectiveness as well as safety. PARP inhibitors work by blocking one of the pathways by which tumor cells repair their damaged DNA.

Patients with this type of ovarian cancer have participated in a trial led by Dana-Farber investigators that tests an anti-body-based therapy known as MM-121 in combination with a weekly dose of the chemotherapy  agent taxol. This study has completed enrollment and results are pending. A separate trial focuses on the drug alisertib, a kinase-blocker, with and without the drug paclitaxel; and yet another compares weekly taxol with a drug called cabozantinib, which blocks the proteins cMET and VEGFR2. This study also is open to women with platinum-resistant cancer.

In a recently completed trial, Dana-Farber investigators tested the combination of two agents, cediranib and olaparib, in patients with recurrent ovarian cancer that was initially platinum-sensitive. Cediranib is an “angiogenesis inhibitor” which may hamper cancer cells’ growth by interfering with their blood supply; olaparib prevents cancer cells from growing abnormally. Patients were randomly assigned to receive both agents or olaparib alone. Researchers hope to announce the results of the study by 2014. Dana-Farber researchers are currently enrolling patients in a phase 1 study of a combination of olaparib and an agent known as BKM120, a tandem that has shown anticancer activity in preclinical studies.

Other trials are open to patients with recurrent ovarian cancer that was initially either platinum-sensitive or platinum-resistant. In one such study, the agent vintafolide, which targets the folic acid receptor on ovarian tumor cells, is being tested in combination with standard chemotherapy, compared to the chemotherapy agent alone.

For a complete list of clinical trials for patients with advanced, recurrent ovarian cancer, visit the National Cancer Institute website.

Ursula Matulonis, MD, is the medical director of Gynecologic Oncology in the Susan F. Smith Center for Women’s Cancers at Dana-Farber.