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Amid PARP Advances, Chemo Remains Critical in Ovarian Cancer

Gina Columbus @ginacolumbusonc
Published: Tuesday, Apr 11, 2017

Heather Dalton, MD

Heather Dalton, MD

In the frontline setting, chemotherapy regimens are still the go-to option for patients with ovarian cancer—and likely will be for years to come, explains Heather Dalton, MD.

While PARP inhibitors, such as rucaparib (Rubraca) and niraparib (Zejula), have demonstrated impressive results in later lines of therapy, a carboplatin/paclitaxel regimen is still holding the reigns as a first-line treatment.

Dalton adds that researchers continue to wait for long-term survival data from the Gynecologic Oncology Group (GOG)-252 trial, in which preliminary findings did not demonstrate that intraperitoneal (IP) chemotherapy was superior to an intravenous (IV) regimen.

In an interview during the 2017 OncLive® State of the Science Summit on Ovarian Cancer, Dalton spoke about the first-line treatment options currently available for patients, pivotal data that have solidified standard approaches, and why chemotherapy will likely always remain critical in the ovarian cancer sphere.

OncLive: What are the options for patients in the first-line setting with ovarian cancer?

Dalton: Unfortunately, most of our patients with ovarian cancer are advanced when they are diagnosed, so we are always left with a conundrum on how to treat them. There has been a lot of research done about the best way to treat these patients. We have moved a long way from initially doing cytotoxic doxorubicin, to around 2003 where carboplatin and paclitaxel became the backbone for our ovarian cancer treatment. Since then, we’ve been looking at different ways to give it and ways to improve progression-free survival (PFS).

Unfortunately, some of those trials have had more success than others. The trial that led to our new standard of therapy was GOG-172, which looked at IV carboplatin and paclitaxel versus IP therapy. The IV method results in significant PFS and (overall survival) OS. That became our new standard of care and we were very excited about.

Subsequently, we have tried to combine that with different types of chemotherapy and different ways to give it. One of those was first actually done in Japan; they looked at giving standard IV chemotherapy compared with what we called dose-dense therapy—which is giving weekly paclitaxel in combination with carboplatin on day 1. We saw a significant improvement with PFS and OS in that study, so we were all very excited about that because the OS difference was even more so than we initially saw in GOG-172.

That was a little bit limited because it was a Japanese study, so how much does that directly apply to our populations here? That population has more clear cell histology, while Americans have more serous histology. Those are some constant criticisms of the study.

Therefore, we repeated that study here in the form of GOG-262, but we added bevacizumab (Avastin). Unfortunately, the bevacizumab seems to have muddied the waters. Most patients got bevacizumab; however, those patients did not experience that big of a difference in OS that we were hoping for. In the subgroup that didn’t actually receive bevacizumab, that improvement in OS was still significant. Basically, we concluded that bevacizumab doesn’t really help in this setting. 

Now, we have 2 kinds of conflicting studies—dose-dense and IP—that have never been compared. That was the trial that we were all looking forward to so much, which was GOG-252, that compared standard chemotherapy versus IP chemotherapy plus the dose-dense therapy. We thought this would answer all of our questions that we had and, because bevacizumab saw good results in some trials, we added bevacizumab to the mix. Unfortunately, while the data is not mature, there doesn’t look to be any improvement in PFS in those groups. 

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