On 13 November 2020, the US Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co.) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumours express PD-L1 (CPS \u226510) as determined by an FDA approved test.<\/p>\n
FDA also approved the PD-L1 IHC 22C3 pharmDx (Dako North America, Inc.) as a companion diagnostic for selecting patients with TNBC for pembrolizumab.<\/p>\n
Approval was based on KEYNOTE-355 (NCT02819518), a multicentre, double-blind, randomised, placebo-controlled study in patients with locally recurrent unresectable or metastatic TNBC, who had not been previously treated with chemotherapy in the metastatic setting. Patients were randomised (2:1) to receive pembrolizumab 200 mg on day 1 every 3 weeks or placebo in combination with different chemotherapy treatments (paclitaxel protein-bound, or paclitaxel, or gemcitabine plus carboplatin) via intravenous infusion.<\/p>\n
The main efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent review according to RECIST v1.1, tested in the subgroup of patients with CPS \u226510. Median PFS was 9.7 months (95% confidence interval [CI] 7.6, 11.3) in the pembrolizumab plus chemotherapy arm and 5.6 months (95% CI 5.3, 7.5) in the placebo arm (hazard ratio 0.65; 95% CI 0.49, 0.86; one-sided p-value = 0.0012).<\/p>\n
The most common adverse reactions (incidence \u226520%) in patients receiving pembrolizumab plus chemotherapy in KEYNOTE-355 were fatigue, nausea, diarrhoea, constipation, vomiting, alopecia, rash, cough, decreased appetite, headache. The most common laboratory abnormalities (incidence \u226520%) in patients receiving pembrolizumab plus chemotherapy were anaemia, leukopaenia, neutropaenia, lymphopaenia, thrombocytopenia, elevated ALT and AST, hyperglycaemia, hypoalbuminaemia, increased alkaline phosphatase, hypocalcaemia, hyponatraemia, hypophosphataemia, and hypokalaemia.<\/p>\n
The recommended pembrolizumab dose for adult patients with locally recurrent unresectable or metastatic TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months. When given with pembrolizumab, either paclitaxel protein bound 100 mg\/m2 on days 1, 8 and 15 every 28 days, or paclitaxel 90 mg\/m2 on days 1, 8 and 15 every 28 days, or gemcitabine 1000 mg\/m2 plus carboplatin AUC 2 mg\/mL\/min on Days 1 and 8 every 21 days is administered via intravenous infusion.<\/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 This application was granted accelerated approval based on PFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.<\/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