The FDA approved the PD-1 inhibitor pembrolizumab as a second-line treatment for patients with recurrent or metastatic cervical cancer who expressed PD-L1 with a combined positive score of at least 1. The approval was based on results of a phase II trial in which patients treated with the drug had an objective response rate of 14.3%.

In June, the FDA approved the PD-1 inhibitor pembrolizumab (Keytruda; Merck) as a second-line treatment for patients with recurrent or metastatic cervical cancer whose tumors express PD-L1. It's the first such drug approved for a gynecologic cancer.

The FDA concurrently approved the PD-L1 IHC 22C3 pharmDx Kit (Dako) as a companion diagnostic.

Currently, patients with advanced cervical cancer receive chemotherapy, often in combination with bevacizumab (Avastin; Genentech), says Charles Drescher, MD, of Fred Hutchinson Cancer Research Center in Seattle, WA. However, few patients are cured by first-line treatment, and second-line options have been a “potpourri of dealer's choice of modestly active drugs,” he says.

“Fortunately, in the U.S., cervical cancer is not a particularly common disease, and metastatic disease is even less common,” he says, but a better second-line treatment option “is an urgent need for the population—there really are no [effective] alternatives.”

Pembrolizumab was approved based on results of the ongoing phase II KEYNOTE-158 trial, a basket trial testing its activity in 11 types of advanced solid tumors. In the cervical cancer arm, 77 of 98 patients expressed PD-L1 with a combined positive score of at least 1 (the ratio of the number of PD-L1–expressing tumor and infiltrating immune cells to the total number of tumor cells). Patients were treated with the drug after chemotherapy and had an objective response rate (ORR) of 14.3%, with 11.7% partial responses and 2.6% complete responses. Of the patients who responded, 10 of 11 responded for at least 6 months.

“It's a whole new option that we just didn' t have [before],” Drescher says, adding that because pembrolizumab is already approved for so many other indications, “its toxicity profile is well known, it's not hard to deliver, and it's available most anywhere, so I think that it' ll be very rapid clinical uptake.”

For Krishnansu Tewari, MD, of the University of California, Irvine, in Orange, who, on behalf of the NCI-sponsored Gynecologic Oncology Group, ran the trial that led to bevacizumab's approval in 2014, any option for patients at high risk for progression and death “is a good thing.”

However, he notes that he is not overly impressed with the ORR and points out that although most women with squamous cervical cancer express PD-L1, that isn' t necessarily true for patients with other histologies, such as adenocarcinoma.

“To an extent, it will change practice because we have nothing else, but we need to do better,” he says, adding that researchers are exploring other options.

For example, the AIM2CERV study is evaluating the use of maintenance axalimogene filolisbac (ADXS11-001; Advaxis), a Listeria-based immunotherapy, following first-line therapy, and Iovance Biotherapeutics is conducting a phase II trial of LN-145, an adoptive T-cell therapy with autologous tumor-infiltrating lymphocytes. Additionally, Genentech is running clinical trials on its PD-L1 inhibitor atezolizumab (Tecentriq).

Other clinical trials are investigating combination therapy for cervical cancer, including pembrolizumab plus chemotherapy and radiation, and AstraZeneca's durvalumab (Imfinzi) plus tremelimumab and radiation.

“When the Gynecologic Oncology Group did the [bevacizumab] study, no one was doing any work in the cervix cancer field, and now there's probably 10 different studies going on,” Tewari says. “Hopefully one of these new treatments will be even more effective.” –Catherine Caruso

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