Jason Luke, MD, FACP, Director, Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center speaks about FDA Approves Merck"™s KEYTRUDA® (pembrolizumab) as Adjuvant Treatment for Adult and Pediatric (≥12 Years of Age) Patients With Stage IIB or IIC Melanoma Following Complete Resection.
The US Food and Drug Administration (FDA) has approved Merck’s anti-PD-1 medication, KEYTRUDA, for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB or IIC melanoma following full resection. The FDA also increased the indication for KEYTRUDA as an adjuvant treatment for stage III melanoma after full resection to include pediatric patients (12 years and older).
The approval in stage IIB and IIC melanoma is based on results from the first interim analysis of Phase 3 KEYNOTE-716 study, which indicated that KEYTRUDA reduced the risk of disease recurrence or death by 35% (HR=0.65 [95 percent CI, 0.46-0.92]; p=0.0132) compared to placebo. For neither group, the median RFS was not reached. After a median follow-up of 14.4 months, 11 percent of KEYTRUDA patients (n=54/487) experienced recurrence or died, compared to 17 percent (n=82/489) of placebo patients. Extrapolation of efficacy findings from adults to pediatric patients (12 years and older) with stage IIB, IIC, and III melanoma is supported by similar biology, pharmacology of therapeutic effect, and exposure-response for efficacy and safety.
Immune-mediated adverse reactions, which can be severe or fatal, can affect any organ system or tissue, and they can affect many body systems at the same time. Pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic responses, solid organ transplant rejection, and problems of allogeneic hematopoietic stem cell transplantation are all immune-mediated adverse effects that can develop during or after treatment with KEYTRUDA. The list of important immune-mediated adverse reactions may not cover all serious and deadly immune-mediated adverse events. To ensure that KEYTRUDA is used safely, it is critical to identify and address immune-mediated adverse events as soon as possible. KEYTRUDA should be withheld or permanently discontinued, and corticosteroids should be supplied if necessary, depending on the severity of the adverse response. Infusion-related responses to KEYTRUDA might be serious or life-threatening. When given to a pregnant woman, KEYTRUDA has the potential to harm the fetus due to its mechanism of action. See “Selected Important Safety Details” below for more information.
KEYNOTE-716 Study Design and Additional Data
The multicenter, randomized (1:1), double-blind, placebo-controlled Phase 3 trial KEYNOTE-716 (ClinicalTrials.gov, NCT03553836) involved 976 patients with fully resected stage IIB or IIC melanoma. Patients were given KEYTRUDA 200 mg or KEYTRUDA 2 mg/kg intravenously (up to a maximum of 200 mg) every three weeks, or placebo, until disease recurrence or intolerable toxicity. The AJCC ninth edition T Stage (>2.0-4.0 mm with ulceration vs. >4.0 mm without ulceration vs. >4.0 mm with ulceration) was used to stratify the randomization. Prior to study admission, patients must not have received any treatment for melanoma other than complete surgical excision of their melanoma. The investigator-assessed RFS was the primary efficacy outcome measure (defined as the time between the date of randomization and the date of first recurrence [local, in-transit, or regional lymph nodes or distant recurrence] or death, whichever occurred first). The definition of RFS was changed to exclude new primary melanomas. Patients were imaged every six months for the first year following randomization, every six months for the next two years, and once in year five following randomization or until recurrence, whichever happened first.
Adverse effects in patients with stage IIB or IIC melanoma were similar to those seen in the 1,011 patients with stage III melanoma who participated in KEYNOTE-054 or the 2,799 patients with melanoma or NSCLC who received KEYTRUDA as a single drug. See “Selected Important Safety Details” below for more information.