On 21 March 2022, the US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck), as a single agent, for patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.<\/p>\n
The FDA also approved the VENTANA MMR RxDx Panel (Ventana Medical Systems \/ Roche Tissue Diagnostics) as a companion diagnostic device to select patients with dMMR in solid tumours that are eligible for treatment with pembrolizumab. The FDA previously approved the FoundationOne CDx (F1CDx, Foundation Medicine, Inc.) as a companion diagnostic device to select patients with MSI-H in solid tumours that are eligible for treatment with pembrolizumab.<\/p>\n
Efficacy was evaluated in KEYNOTE-158 (NCT02628067), a multicentre, non-randomised, open-label, multi-cohort study in 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma in Cohorts D and K. MSI or MMR tumour status was determined using polymerase chain reaction or immunohistochemistry, respectively. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression. Patients treated with pembrolizumab without disease progression could be treated for up to 24 months.<\/p>\n
The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR was 46% (95% confidence interval 35, 56). Median DoR was not reached (2.9, 55.7+), with 68% having response durations \u226512 months and 44% having response durations \u226524 months.<\/p>\n
The most common adverse reactions (\u226520%) occurring in patients were fatigue, musculoskeletal pain, rash, diarrhoea, pyrexia, cough, decreased appetite, pruritis, dyspnoea, constipation, pain, abdominal pain, nausea, and hypothyroidism. Immune-mediated side effects are also associated with pembrolizumab; these include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.<\/p>\n
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.<\/p>\n
Full prescribing information for Keytruda is available here<\/a>.<\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n