FDA Grants Accelerated Approval to Pembrolizumab, Chemo Combo for Locally Recurrent Unresectable or Metastatic TNBC

The FDA has granted accelerated approval to pembrolizumab (Keytruda) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test.

In addition, the agency also approved the PD-L1 IHC 22C3 pharmDx as a companion diagnostic for selecting patients with TNBC for pembrolizumab.

The FDA approval was based on data from the multicenter, double-blind, randomized, placebo-controlled KEYNOTE-355 trial (NCT02819518), which evaluated patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting.

Patients were randomized 2:1 to receive 200 mg of pembrolizumab 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. The primary end point for the study was progression-free survival (PFS) as assessed by blinded independent review according to RECIST 1.1, tested in the subgroup of patients with CPS of 10 or higher.

Median PFS was 9.7 months (95% 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 (HR, 0.65; 95% CI, 0.49-0.86; one-sided P = .0012).

Regarding safety, the most common adverse events observed in patients receiving pembrolizumab plus chemotherapy in KEYNOTE-355 (≥20% of patients) were fatigue, nausea, diarrhea, constipation, vomiting, alopecia, rash, cough, decreased appetite, and headache. Further, the most common laboratory abnormalities in patients receiving pembrolizumab plus chemotherapy (incidence ≥20%) were anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, elevated ALT and AST, hyperglycemia, hypoalbuminemia, increased alkaline phosphatase, hypocalcemia, hyponatremia, hypophosphatemia, and hypokalemia.

The FDA recommended dose of pembrolizumab 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 should be administered via intravenous infusion.

Of note, this application was granted accelerated approval based on PFS. However, continued approval for this indication may be dependent upon verification and description of clinical benefit in the confirmatory trials.

Reference:

FDA grants accelerated approval to pembrolizumab for locally recurrent unresectable or metastatic triple negative breast cancer [news release]. FDA. Published November 13, 2020. Accessed November 13, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-pembrolizumab-locally-recurrent-unresectable-or-metastatic-triple?utm_medium=email&utm_source=govdelivery