Survival Benefit With GI-Based Adjuvant Chemotherapy Regimen in Mucinous Ovarian Cancer

Katherine C. Kurnit, MD

Data from a retrospective study suggests an adjuvant gastrointestinal (GI)-based chemotherapy regimen is more beneficial than one that is gynecologic-based in patients with mucinous ovarian cancer, said Katherine C. Kurnit, MD.¹

“Right now, mucinous ovarian cancer is treated a lot like other epithelial ovarian cancers,” said Kurnit, lead author and a fellow in gynecologic oncology at The University of Texas MD Anderson Cancer Center. “A lot of our data are from other mostly high-grade serious ovarian cancer patients, and so, we usually use routine gynecologic-based regimens, which is carboplatin and paclitaxel, most recently.”

However, because outcomes for patients with mucinous ovarian cancer are poor, researchers have been working on exploring other approaches to better treat this subtype of patients. For example, the GOG 241 study looked at the use of carboplatin/paclitaxel with or without bevacizumab (Avastin) or oxaliplatin/capecitabine with or without bevacizumab in chemotherapy-naïve patients with mucinous ovarian cancer, including those with recurrent stage I disease. Unfortunately, the trial was stopped early in 2013 due to poor accrual—50 patients were enrolled—and thus, researchers were unable to make any conclusions.²

Keeping this in mind, Kurnit and her team at The University of Texas MD Anderson Cancer Center collaborated with researchers of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine and conducted a retrospective cohort study to determine whether the use of a GI-based regimen would be associated with a difference in survival compared with use of a gynecologic-based regimen in patients with mucinous ovarian cancer who received postoperative adjuvant chemotherapy.

Results suggested an improvement in progression-free survival (PFS) in patients who received a GI-based treatment (not reached) compared with that of a gynecologic type (26 months;P= .04). Overall survival (OS) was also improved with a GI regimen, with which the median OS was not reached versus 67 months with a gynecologic-based treatment (P= .02). However, the role of bevacizumab in these regimens remains unclear, Kurnit explained.

In an interview withTargeted Oncologyduring the 2019 SGO Annual Winter Meeting, Kurnit discussed the clinical implications of these findings and where research should go in the future.

TARGETED ONCOLOGY: Could you discuss the GOG 241 trial and the challenges that were faced?

Kurnit:Because patients [with mucinous ovarian cancer] may not respond as well to many of the routine regimens as patients with high-grade serious ovarian cancer, the Gynecologic Oncology Group (GOG) put together a trial that specifically [focused on] patients with mucinous ovarian cancer, and looked at whether a GI-type regimen might [lead to] better survival outcomes for these patients.

They were looking at survival outcomes, comparing a gynecologic-type regimen with and without bevacizumab and a GI-type regimen with and without bevacizumab, and they had 4 different arms that they were investigating.

They opened, and unfortunately, didn’t accrue very well, so they ended up having to close early. When they looked back at the patients who were enrolled, they found that a lot of them did not actually have primary ovarian cancer, and many of them were metastatic from mostly GI sites. Therefore, the study itself was limited by difficulties accruing, but also in the patients with unintended nonovarian cancer who were enrolled.\

TARGETED ONCOLOGY:What was the rationale behind your study?

Kurnit:For our study, we wanted to further investigate this question and see if we had enough patients that we could see, from a retrospective cohort study design, whether there would be a difference between these 2 regimens.

There, we at The University of Texas MD Anderson Cancer Center collaborated with the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine and reviewed our patients with mucinous ovarian cancer from the past several decades. We just looked back to see which regimens they received, [noting if] they received bevacizumab, and compared outcomes for those who had received a gynecologic-type regimen versus a GI-type regimen. Other groups have probably looked at their data, but this is probably the largest group trying to evaluate this specific question since that GOG trial completed.

TARGETED ONCOLOGY:What were your methods?

Kurnit:Our goal was to compare GI-type regimens—those including capecitabine, 5-fluorouracil, oxaliplatin, or some sort of combination—with the gynecologic-based regimens, which is a carboplatin- or cisplatin-based regimen, usually with a taxane. Then, they were allowed to have bevacizumab or not.

Because this is retrospective, we didn’t have any control over what regimens they received but we did have the information about what each patient received in terms of their chemotherapy. Our outcomes were to look at progression-free survival (PFS) and overall survival (OS) and compare between those 2 major subsets of chemotherapy types. The question about bevacizumab is a difficult one, and that was one that the GOG trial was trying to evaluate as well. Our numbers were not big enough that we could actually answer that question, but it’s notable that the vast majority of patients who had received a gynecologic regimen did not receive bevacizumab, and that may be a product of the years that these patients were being treated.

[In those who received] the GI-type regimens, about half of them did receive bevacizumab. Although our study is probably too small to compare, we think even in those patients who did not receive bevacizumab, the GI-based regimens seemed to offer some improvement in survival.

When we looked at PFS and OS, comparing those who received a gynecologic-based regimen with a GI-based regimen, the GI regimen patients did seem to do significantly better both in terms of PFS and OS. These were unexpected findings in that we didn’t think that the difference would be quite that significant, but we think this is really promising.

We all wondered and hypothesized that GI-type regimens potentially might lead to better outcomes, but because our GYN patients are historically receiving these more platinum-based regimens—specifically carboplatin, cisplatin, taxane-based regimens—we don’t have as much experience using these GI-type regimens. If this is something that we are going to consider doing in the future, it’s going to change how we approach these patients and what considerations we have for chemotherapy in the adjuvant setting.

TARGETED ONCOLOGY:What is the take-home message from this research? What are the next steps?

Kurnit:These data suggest that there may be a benefit to using a GI-type regimen—one including oxaliplatin, capecitabine, and potentially 5-FU—and that the role of bevacizumab is unclear at this point. Ideally, we would have those prospective studies, but the GOG 241 trial showed us that it’s going to be difficult to accrue and complete those studies without a lot of changes and funding.

Other potential options to explore would be trying to do these large multicenter collaborations, potentially even registry studies, where we’re looking at patients prospectively enrolled, evaluating the regimens they’re receiving, and how their outcomes are to get a large number of patients and get at some of these subgroups.

At The University of Texas MD Anderson Cancer Center, we are starting to collect our own data prospectively continuing to look at the patients who come in with mucinous ovarian cancer and other rare subtypes, and I’m sure other groups around the country are doing that as well. However, in terms of any specific next steps, I’m not sure that anything has been formally implemented yet.

References:

1. Kurnit KC, Sinno A, Fellman BM, et al. Gastrointestinal adjuvant chemotherapy regimens improve survival outcomes in women with mucinous ovarian cancer. In: Proceedings from the 2019 SGO Annual Winter Meeting; January 17-19, 2019; Lake Tahoe, CA.
2. Gore ME, Hackshaw A, Brady WE, et al. Multicentre trial of carboplatin/paclitaxel versus oxaliplatin/capecitabine, each with/without bevacizumab, as first line chemotherapy for patients with mucinous epithelial ovarian cancer (mEOC).J Clin Oncol. 2015;33(15):5528-5528.