James Tate Thigpen, MD
Although ovarian cancer remains a formidable challenge in the United States, therapeutic advances achieved during the past several years have provided specialists in gynecologic malignancies with more options than ever for treating patients.
These options were explored by a panel of experts in a recent OncLive
Peer Exchange discussion entitled “Emerging Concepts in Advanced Ovarian, Fallopian, Peritoneal, and Cervical Cancers.” The discussion was moderated by James Tate Thigpen, MD, a leader in the field whose work has helped define the most effective uses of chemotherapy for patients.
“I think this is a great time for us in the GYN oncology sphere for the development of new drugs and integration of these drugs into practice,” said panelist Robert L. Coleman, MD. “I’m very excited. The precision medicine field is just exploding. We’re excited to see it develop.”
Angeles Alvarez Secord, MD, noted that the FDA drug approvals for patients with ovarian cancer in 2014—the PARP inhibitor olaparib (Lynparza) and the antiangiogenic antibody bevacizumab (Avastin)—marked the first new agents in the malignancy since 2006.
“We’ll see how these agents can improve care for our patients clinically,” she said. “Biomarkers are going to help us identify patients who are most likely to benefit from these agents and improve survival, and that’s really what this is all about.”
BRCA and Other Biomarkers
The category of ovarian cancer encompasses malignancies of the fallopian tubes, peritoneum, and ovaries, and is comprised of five histologic subtypes, explained Bradley J. Monk, MD. These subtypes consist of clear cell, endometriod, mucinous (rare subtypes unresponsive to chemotherapy), and low- and high grade serous (the most common subtype).
Robert L. Coleman, MD
These histologies are further classified as type I or II based on whether or not they display high-grade characteristics in either clinicopathologic or molecular features. Low-grade serous tumors in the fallopian tubes, peritoneal, and ovaries have molecular perturbations in the mitogen-activated protein (MAP) kinase pathway, while high-grade tumors are characterized by TP53
mutations, said Monk. In addition, there are multiple subtypes within each subtype.
Thus, ovarian cancer represents a very heterogeneous disease with “a lot of genomic chaos” in these tumors, noted Coleman. One consequence of the existence of these subtypes, he explained, is that while the current indication for olaparib specifies patients with more than three lines of prior therapy who are germline positive for BRCA mutations, study findings potentially open up the PARP class of agents to other populations.
High-grade tumors can be bifurcated based on the BRCA
gene alterations or genes related to BRCA
, said Monk. The National Comprehensive Cancer Network recommends that women with ovarian cancers, regardless of family history, age of onset, and histologic subtype, should be tested for BRCA
mutations. Newer data show that women with non-serous cancers also express a high prevalence of BRCA1
mutations and other homologous recombination defects, noted Alvarez Secord.
Bradley J. Monk, MD
At present, testing for everything other than BRCA
mutations may yield information that is not immediately clinically useful, Thigpen pointed out. Even within the realm of BRCA mutations, however, there are complexities.