Combinations May Be the Future of Immunotherapy in Ovarian Cancer

To date, trials testing the use of immunotherapy in the treatment of ovarian cancer yielded disappointing results. However, researchers are not giving up. Instead, they’re investigating to see if immunotherapy drugs — such as PD1 and PDL-1 inhibitors – can be combined with other agents to benefit patients.

“Ovarian cancer is a highly unmet medical need. Most cases are diagnosed in advanced stages, and most cases recur,” Bradley J. Monk, M.D., professor and director of the Division of Gynecologic Oncology at Creighton University at St. Joseph’s Hospital and Medical Center in Phoenix, told OncLive, a sister publication of CURE. “We need agents such as immuno-oncology agents to help patients live better and longer.”

Aside from microsatellite instability-high (MSI-H) or mismatch-repair deficient endometrial cancers, there are currently no FDA-approved immunotherapy agents in this space. Previous studies have evaluated a variety of monotherapies for this patient population — including Opdivo (nivolumab), Keytruda (pembrolizumab), Bavencio (avelumab), Imfinzi (durvalumab) and Tecentriq (atezolizumab) – however, they induced insignificant clinical outcomes.

“I am sorry to say that the single-agent activity of these PD-1/PD-L1 molecules is only between 10 to 15 percent,” Monk said. “Therefore, we are now studying combinations. The idea is to enhance the activity of these checkpoint inhibitors.”

There are five phase 3 clinical trials that are testing combination regimens that include at least one checkpoint blockade drug. Of the five trials, two are investigating combination regimens that include Bavencio and three are looking into Tecentriq.

“The idea is to enhance the activity of these checkpoint inhibitors — converting what we call cold tumors to hot tumors, and there are two strategies,” said Monk. “The first is to add immunogenic chemotherapy and an anthracycline, such as pegylated liposomal doxorubicin, or carboplatin/paclitaxel. The other strategy is adding a PARP inhibitor.”

The JAVELIN Ovarian 200 trial, which has enrolled 550 patients with platinum-resistant, recurrent ovarian cancer, will be the first randomized trial to have its results reported. This study is investigating outcomes in patients treated with Bavencio alone compared with Bavencio plus Pegylated Liposomal Doxorubicin and with Pegylated Liposomal Doxorubicin alone.

In the JAVELIN Ovarian 100 trial, 950 patients with untreated, epithelial ovarian cancer are expected to enroll. Patients will be randomized to receive either Bavencio plus carboplatin and paclitaxel or chemotherapy alone in the frontline setting.

The other three trials will be looking into triplet combinations using chemotherapy, Avastin (bevacizumab) — an anti-VEGF therapy – and Tecentriq.

“It’s a very exciting time, and very ambitious,” Monk said.

For now, there are no safety contradictions that researchers are concerned about, though investigation is still in the early stages. More research is needed not only to figure out the potential safety and side effect profile, but also the best ways, in general, to use immunotherapy agents in ovarian cancer treatment.

“It is exciting, but it will only be personally satisfying if we can bring these medicines to patients and prove that they are both efficacious and safe,” Monk said.