August 2021: Pembrolizumab (Keytruda, Merck) was approved by the FDA for high-risk, early-stage triple-negative breast cancer (TNBC) as a neoadjuvant treatment in combination with chemotherapy, and later as a single agent as adjuvant treatment following surgery.
Pembrolizumab in conjunction with chemotherapy was also given regular approval by the FDA for patients with locally recurrent unresectable or metastatic TNBC whose tumours express PD-L1 (Combined Positive Score [CPS] 10) as assessed by an FDA-approved test. In November 2020, the FDA gave pembrolizumab expedited approval for this indication.
The neoadjuvant and adjuvant approvals, as well as the confirmatory trial for the accelerated approval, were based on the following trial.
In KEYNOTE-522 (NCT03036488), a randomised, multicenter, double-blind, placebo-controlled trial involving 1174 patients with newly diagnosed previously untreated high-risk early-stage TNBC (tumour size >1 cm but 2 cm) and continued adjuvant treatment with pembrolizumab as a single agent, the efficacy of pembrolizumab in combination with neoadjuvant chemotherapy followed by surgery and continued Patients were included regardless of PD-L1 expression in their tumours.
Pembrolizumab in conjunction with chemotherapy or placebo in combination with chemotherapy were given to patients in a 2:1 ratio. The chemotherapy protocol is detailed in the drug label, which is linked below.
The pathological complete response (pCR) rate and event-free survival were the primary efficacy outcome metrics (EFS). Patients who received pembrolizumab in conjunction with chemotherapy had a pCR rate of 63 percent (95 percent CI: 59.5, 66.4), compared to 56 percent (95 percent CI: 50.6, 60.6) for patients who got chemotherapy alone. The proportion of patients who had an EFS episode was 123 (16%) and 93 (24%), respectively (HR 0.63; 95 percent CI: 0.48, 0.82; p=0.00031).
Fatigue/asthenia, nausea, constipation, diarrhoea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia were the most common adverse reactions reported in approximately 20% of patients in trials of pembrolizumab in combination with chemotherapy.
Pembrolizumab is given as an intravenous infusion over 30 minutes at a dose of 200 mg every three weeks or 400 mg every six weeks for TNBC. For neoadjuvant treatment, pembrolizumab is given in combination with chemotherapy for 24 weeks, and then as a single agent for adjuvant treatment for up to 27 weeks.
