ASCO 2010 Ovarian Advances

Dr. Susan Ellard, FRCPC, BC Cancer Agency, Southern Interior

There were 58 women enrolled overall. Of the 25 women in the FTZ alone arm, results showed about three quarters had a decrease or stabilization in their CA125 marker for 3-6 months or longer. Of 44 women treated with chemo plus FTZ, 39 had Ca125 return to normal and 9 of those had a longer remission with FTZ+ chemo than they had obtained with first-line chemotherapy, which is unusual, as the length of remission tends to decrease over time in almost all patients who have relapsed. 3 of those 9 women have continued on to take FTZ by itself after the combination with remissions now lasting more than 3 years in some cases. These results though very notable, were seen in a select small group of women only thus a larger study is underway to assess the impact of FTZ with chemotherapy in first relapse.

PARP Inhibitor

Finally, another new class of drug, called a PARP inhibitor, was presented in a study by BC Cancer Agency's own Dr. Karen Gelmon. A number of PARP inhibitors are under study, and are of particular interest in women with inherited BRCA 1 or 2 mutations, which are known to cause a very high risk for breast and/or ovarian cancer. Researchers have anticipated the type of mutation present in the DNA of women with inherited mutations would make their tumors more vulnerable to a PARP inhibitor. The DNA changes in these women's cancers would likely make it harder for their cancer cells to repair damage caused by PARP inhibitors, or by PARP inhibitors in combination with chemotherapy.

This study tested an oral PARP inhibitor, olaparib, by itself, in women with breast or ovary cancer, which was either affecting women with identified inherited BRCA mutations, or women not yet assessed for the presence of an inherited mutation. There were 10 women with known mutations, and 54 with unknown status, in the ovary cancer group. In the small group with known BRCA mutation, 40% responded to olaparib and in the unknown group, 26% did. When BRCA testing was done on the unknown group, 7 of 54 were found to have inherited mutations. When women were then re-grouped according to having or not having a BRCA mutation, after testing, there was about a 41% response rate in the BRCA mutation group, and still about a 24% response rate, in the group without an inherited mutation. 14 women still remain on treatment on the study, continuing to do well on olaparib. These findings may indicate DNA changes in serous ovarian tumors are similar to those some women inherit, in high-risk families. This is being studied very closely.

Disappointingly, women with breast cancer who were either in association with a BRCA mutation, or were triple negative (a type of breast cancer more often seen in women with BRCA mutations) showed no significant benefits with olaparib in this study. 25 women with breast cancer were studied. The reasons for this lack of effect in breast cancer are not currently well understood.