The FDA has approved Merck’s Keytruda, the company’s anti-PD-1 therapy, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
This indication is approved under the FDA’s accelerated approval regulations based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
“Keytruda is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This approval also marks the first indication for Keytruda in a gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women.”
Immune-mediated adverse reactions occurred with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, and solid organ transplant rejection. Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate.
“Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer,” said Dr. 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. “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.”
“This approval is welcome news for patients, who now have another option in their fight against this serious disease,” said Tamika Felder, founder and chief visionary officer, Cervivor.
Data Supporting the Approval
The efficacy of Keytruda was investigated in 98 patients with recurrent or metastatic cervical cancer enrolled in a single cohort (Cohort E) in study KEYNOTE-158, a multi-center, non-randomized, open-label, multi-cohort trial. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression. Patients were treated with Keytruda intravenously at a dose of 200 mg every three weeks until unacceptable toxicity or documented disease progression.
Patients with initial radiographic disease progression could receive additional doses of treatment during confirmation of progression unless disease progression was symptomatic, was rapidly progressive, required urgent intervention, or occurred with a decline in performance status. Patients without disease progression could be treated for up to 24 months.
Assessment of tumor status was performed every nine weeks for the first 12 months, and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by blinded independent central review, and duration of response (DOR).
Among the 98 patients in Cohort E, 77 (79 percent) had tumors that expressed PD-L1 with a CPS ≥1 and received at least one line of chemotherapy in the metastatic setting. PD-L1 status was determined using the PD-L1 IHC 22C3 pharmDx Kit. The baseline characteristics of these 77 patients were: median age was 45 years (range, 27 to 75 years); 81 percent were White, 14 percent Asian, and three percent Black; ECOG PS was 0 (32 percent) or 1 (68 percent); 92 percent had squamous cell carcinoma, six percent adenocarcinoma, and one percent adenosquamous histology; 95 percent had M1 disease and five percent had recurrent disease; 35 percent had one and 65 percent had two or more prior lines of therapy in the recurrent or metastatic setting.
For the 77 patients whose tumors expressed PD-L1 with a CPS ≥1, the ORR was 14.3 percent (95 percent CI, 7.4-24.1), with a complete response rate of 2.6 percent and partial response rate of 11.7 percent. Among the 11 responding patients, median DOR was not yet reached (range, 4.1 to 18.6+ months) and 91 percent experienced a duration of response of six months or longer. The median follow-up time was 11.7 months (range, 0.6 to 22.7 months). No responses were observed in patients whose tumors did not have PD-L1 expression (CPS<1).
Keytruda was discontinued due to adverse reactions in eight percent of 98 patients (in Cohort E) enrolled with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39 percent of patients receiving KEYTRUDA. The most frequent serious adverse reactions reported included anemia (7 percent), fistula, hemorrhage, and infections [except urinary tract infections] (4.1 percent each). The most common adverse reactions (occurring in ≥20 percent of patients) were fatigue (43 percent), musculoskeletal pain (27 percent), diarrhea (23 percent), pain, abdominal pain (22 percent each), and decreased appetite (21 percent).
(Source: Merck)
Filed Under: Drug Discovery
