On 26 July 2021, the US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck) for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.<\/p>\n
FDA also granted regular approval to pembrolizumab in combination with chemotherapy for patients with locally recurrent unresectable or metastatic TNBC whose tumours express PD-L1 (Combined Positive Score [CPS] \u226510) as determined by an FDA approved test. FDA granted accelerated approval to pembrolizumab for this indication in November 2020.<\/p>\n
The following study was the basis of the neoadjuvant and adjuvant approval, as well as the confirmatory trial for the accelerated approval.<\/p>\n
The efficacy of pembrolizumab in combination with neoadjuvant chemotherapy followed by surgery and continued adjuvant treatment with pembrolizumab as a single agent was investigated in KEYNOTE-522 (NCT03036488), a randomised, multicentre, double-blind, placebo-controlled study conducted in 1174 patients with newly diagnosed previously untreated high-risk early-stage TNBC (tumour size >1 cm but \u22642 cm in diameter with nodal involvement or tumour size >2 cm in diameter regardless of nodal involvement). Patients were enrolled regardless of tumour PD-L1 expression.<\/p>\n
Patients were randomised (2:1) to pembrolizumab in combination with chemotherapy or placebo in combination with chemotherapy. Details of the chemotherapy regimen are in the drug label linked below.<\/p>\n
The main efficacy outcome measures were pathological complete response (pCR) rate and event free survival (EFS). The pCR rate was 63% (95% confidence interval [CI] 59.5, 66.4) for patients who received pembrolizumab in combination with chemotherapy compared with 56% (95% CI 50.6, 60.6) for patients who received chemotherapy alone. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively (hazard ratio 0.63; 95% CI 0.48, 0.82; p = 0.00031).<\/p>\n
The most common adverse reactions reported in \u2265 20% of patients in studies of pembrolizumab in combination with chemotherapy were fatigue\/asthenia, nausea, constipation, diarrhoea, decreased appetite, rash, vomiting, cough, dyspnoea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.<\/p>\n
The recommended dosage of pembrolizumab for TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks as an intravenous infusion over 30 minutes. Pembrolizumab is administered in combination with chemotherapy for neoadjuvant treatment for 24 weeks, and then as a single agent for adjuvant treatment for up to 27 weeks.<\/p>\n
Full prescribing information for Keytruda is available here<\/a>.<\/p>\n This review used the Real-Time Oncology Review pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment. The FDA approved this application approximately 5 months ahead of the FDA goal date.<\/p>\n This application was granted priority review. Pembrolizumab received breakthrough therapy designation for this indication.<\/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