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Avastin and olaparib may get a second chance in ovarian cancers

BY ELIZABETH WHITTINGTON
PUBLISHED SUNDAY, JUNE 3, 2012
Two interesting trials in ovarian cancer were presented yesterday with impressive results and a surprising prediction about their futures.

Avastin (bevacizumab) and olaparib, a PARP inhibitor, were topics of interest at the ovarian cancer oral abstract session on Saturday. While Avastin has seen positive results in previous ovarian cancer studies, this new study tackles a subset of hard-to-treat ovarian cancer. Olaparib has had somewhat of a roller coaster ride in the past years it was seen as a promising treatment for triple-negative breast cancer until a large trial showed it had little benefit in the BRCA-mutation positive population. The company that makes olaparib then switched gears to focus its efforts on testing the drug in ovarian cancer.

AURELIA

Although most cases of ovarian cancer respond to Taxol (paclitaxel) or another platinum-based chemotherapy, about 20 percent of cancers continue to progress with initial treatment while other cases later become resistant or relapse. To tackle these platinum-resistant cancers, a French research group examined adding Avastin (bevacizumab), which aims to cut off the blood supply to growing tumors, to standard chemotherapy.

Avastin has shown benefit in two other previous large trials, but zeroing in on those that don't respond to platinum chemotherapy is a new step. In the AURELIA trial, women whose cancers progressed within six months of their final dose of platinum therapy were randomized to receive chemotherapy with or without Avastin.

Women in the trial were given either Taxol, Doxil (liposomal pegylated doxorubicin) or topotecan, depending on the physician's choice of treatment, while about half also received Avastin. After about a year follow-up, researchers found that fewer women in the Avastin group had a recurrence (75 percent versus 91 percent in the chemotherapy-only group). The addition of Avastin also delayed disease progression by about half. Median progression-free survival was 6.7 month with Avastin compared with 3.4 months. Whether adding Avastin extends survival, however, is not yet known.

Although Avastin appears to work against ovarian cancer, it also increased side effects, including high blood pressure, proteinuria and rare cases of perforations in the intestines.

Olaparib

In the olaparib study, women with advanced platinum-sensitive ovarian cancers were randomized to receive Taxol and carboplatin with or without olaparib. Those in the PARP inhibitor arm were also given maintenance olaparib. Of the 156 patients who received treatment in the study, those in the olaparib arm had longer progression-free survival (12.2 months versus 9.6 months), but as in the AURELIA study, overall survival data has not yet been reached. Common side effects included nausea and vomiting.

Surprisingly, after the researchers presented their data, Michael Seiden, MD, PhD, of Fox Chase Cancer Center, provided the discussion in which he predicted both trials would ultimately turn out to be negative. This wouldn't be the first time where we've seen impressive preliminary data, or one where the progression-free survival benefit was there, but overall survival didn't pan out. But ultimately, the Avastin data appears to promising, and I wouldn't be surprised to see it finally make its way to ovarian cancer patients outside of clinical trials.

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