The FDA has granted pembrolizumab (Keytruda) an accelerated approval for the treatment of patients with advanced, PD-L1–positive cervical cancer with disease progression on or after chemotherapy.
The approval defines PD-L1 positivity as a combined positive score (CPS) of ≥1 as measured by an FDA-approved test.
The FDA based its decision on data from 98 patients with recurrent or metastatic cervical cancer enrolled in a single cohort in the phase II KEYNOTE-158 trial. The global, open-label, nonrandomized, multicohort, multicenter study evaluated pembrolizumab in patients with multiple types of advanced solid tumors who progressed on standard of care therapy.
At a median follow-up of 11.7 months (range, 0.6-22.7), the overall response rate (ORR) was 14.3% (95% CI, 7.4-24.1) in 77 PD-L1–positive patients (CPS ≥1) previously treated with ≥1 line of chemotherapy in the metastatic setting. The ORR comprised a complete response rate of 2.6% and a partial response rate of 11.7%. The median duration of response was not reached (range, 4.1-18.6+), and 91% of responders had a response duration of 6 months or longer.
There were no responses reported for patients with PD-L1 expression of CPS <1.
"Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer,” Bradley Monk, oncologist with Arizona Oncology, medical director of US Oncology Research Gynecology Program and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine, said in a statement.
“The approval of Keytruda in this indication is important news—and as an oncologist, it is exciting to see a much needed option made available to these patients,” added Monk.
Among the 77 PD-L1–positive patients, the median age was 45 years (range 27-75), 32% had an ECOG performance status (PS) of 0, and 68% had an ECOG PS of 1. Eighty-one percent of patients were white, 14% were Asian, and 3% were black. Thirty-five percent of patients had 1 prior line of treatment for recurrent or metastatic disease, and 65% had ≥2 prior lines.
Regarding histology, 92% had squamous cell carcinoma, 6% had adenocarcinoma, and 1% had adenosquamous carcinoma. Ninety-five percent of patients had M1 disease and 5% had recurrent disease. PD-L1 status was determined using the PD-L1 IHC 22C3 pharmDx Kit.
Patients received 200 mg of pembrolizumab every 3 weeks for 24 months or until withdrawal of consent, confirmed radiographic progression, unacceptable toxicity, or investigator decision. Clinically stable patients with radiologic progression could remain on treatment until progression was confirmed by subsequent imaging. Tumors were assessed every 9 weeks for the first year and then every 12 weeks thereafter.
The median exposure to pembrolizumab among all 98 patients was 2.9 months (range, 1 day to 22.1 months).
The most frequently (≥10% of patients) reported all-grade adverse events (AEs) included fatigue (43%), pain (22%), pyrexia (19%), peripheral edema (15%), musculoskeletal pain (27%), diarrhea/colitis (23%), abdominal pain (22%), nausea (19%), vomiting (19%), constipation (14%), decreased appetite (21%), hemorrhage (19%), UTI (18%), infections (16%), rash (17%), hypothyroidism (11%), headache (11%), and dyspnea (10%).
The most common grade 3/4 AEs included UTI (6%), hemorrhage (5%), musculoskeletal pain (5%), fatigue (5%), infections (4.1%), abdominal pain (3.1%), pain (2%), peripheral edema (2%), rash (2%), headache (2%), diarrhea/colitis (2%), vomiting (1%), dyspnea (1%), and pyrexia (1%).
AE-related discontinuations occurred in 8% of patients. Thirty-nine percent of patients experienced serious AEs, with the most frequent being anemia (7%), fistula (4.1%), hemorrhage (4.1%), and infections (except UTIs; 4.1%).
The accelerated approval for pembrolizumab in this setting is contingent on the results of a confirmatory trial.
Pembrolizumab has additional approved indications in melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, urothelial carcinoma, gastric cancer, and microsatellite instability–high solid tumors.
Agilent Technologies also announced in a press release today that the FDA has approved its Dako PD-L1 IHC 22C3 pharmDx assay as a companion diagnostic to identify patients with cervical cancer who are eligible for pembrolizumab based on their PD-L1 expression level. The assay had previously been approved for use in the non–small cell lung cancer and gastric or gastroesophageal junction adenocarcinoma settings.
Keytruda Prescribing Information. https://bit.ly/2HJOeUl. Accessed June 12, 2018.