High-grade serous ovarian carcinoma is the most malignant form of ovarian cancer, with a high recurrence rate and a low survival rate. While patients are commonly treated with induction chemotherapy consisting of paclitaxel plus carboplatin, there is a need to develop additional first- and second-line therapies to increase survival in patients with this disease.
In their study now published in The New England Journal of Medicine, Robert L. Coleman, MD, a Professor in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center, and colleagues found that the addition of veliparib—a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor—to paclitaxel/carboplatin as first line-chemotherapy and as maintenance therapy significantly improved progression-free survival compared with paclitaxel and carboplatin alone. In this interview with i3 Health, Dr. Coleman discusses the benefits of veliparib and other ongoing developments in the treatment of patients with high-grade serous ovarian carcinoma.
What are some of the most challenging aspects of treating patients with stage III or IV high-grade serous ovarian carcinoma?
Robert L. Coleman, MD: One challenge is that these patients are frequently in need of a response to treatment for symptomatic relief. Ultimately, however, the biggest frustration is that while we are generally successful in achieving an initial response to chemotherapy treatment, we cannot effectively prevent recurrence to a reliable or sustainable degree.
How does paclitaxel/carboplatin/veliparib induction therapy followed by veliparib maintenance therapy compare with current treatments for previously untreated stage III or IV high-grade serous ovarian carcinoma?
Dr. Coleman: There are few other direct comparisons to this strategy. The three options available for concomitant treatment following primary cytoreduction surgery are paclitaxel/carboplatin, paclitaxel/carboplatin/bevacizumab, and now—if veliparib is approved—paclitaxel/carboplatin/veliparib. For patients and physicians considering neoadjuvant treatment, the options would be paclitaxel/carboplatin or paclitaxel/carboplatin/veliparib.
In both situations, the additions of bevacizumab or veliparib have improved outcomes in all investigated patient cohorts over paclitaxel/carboplatin alone. The degree of benefit for veliparib is highest in patients with a germline or somatic BRCA gene mutation (g/s BRCA), and the benefit is nearly as good in all patients with homologous-recombination deficiency (HRD). Similar effects in patients with these biomarkers are not predicted for bevacizumab.
When a choice for paclitaxel/carboplatin or paclitaxel/carboplatin/bevacizumab has been made, another option for newly diagnosed women is primary maintenance. Niraparib is an option if it is approved in this situation and the patient has not received bevacizumab during chemotherapy. If the patient has a BRCA mutation and has not been started on veliparib, then olaparib is approved and useful. If the patient has been started on concomitant bevacizumab, adding olaparib is also an option. In each of these cases, the relevant decision tools are the knowledge of a biomarker—g/s BRCA or possibly HRD if it is approved as a complementary diagnostic—and knowing when the decision is to be made.
How do you see the treatment of high-grade serous ovarian carcinoma evolving?
Dr. Coleman: With more biomarker development, cohorts of women will have specific options based on these variables. The number of women receiving PARP inhibitors in the primary setting is expected to increase in the coming years; multiple trials that are currently accruing patients are adding angiogenesis, immune checkpoint inhibitors, and PARP inhibitors in the primary and maintenance settings. Our challenge will be to determine the best sequence of exposure and to determine if re-exposure can still provide a benefit to these patients in preventing recurrence.
Do you have any words of advice for community oncologists and other physicians treating patients with high-grade serous ovarian carcinoma?
Dr. Coleman: Education, education, education. The world just got more complicated with the current crop of new trials. Understanding how biomarkers will impact decision making and how to interpret the value of these new strategies in subgroups of patients will require a lot of attention to details that were not previously needed in order to determine the optimal approach for women with newly diagnosed advanced ovarian carcinoma.
About Dr. Coleman
Robert L. Coleman, MD, is a Professor in the Department of Gynecologic Oncology and Reproductive Medicine and the Ann Rife Cox Chair in Gynecology at the University of Texas MD Anderson Cancer Center in Houston. As the principal investigator for MD Anderson's Gynecologic Oncology Group, he has led numerous clinical trials and authored or coauthored over 400 scientific publications, including peer-reviewed articles, book chapters, and textbooks. Dr. Coleman's research focuses on the development of novel therapies for ovarian, uterine, and cervical cancer.
For More Information
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.