The FDA recently approved pembrolizumab (Keytruda®, Merck & Co) with chemotherapy for patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) for those whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test.
In addition, the FDA approved the companion diagnostic, PD-L1 IHC 22C3 pharmDx (Dako North America, Inc.), to select patients with TNBC for pembrolizumab.
Efficacy was shown in KEYNOTE-355 (NCT02819518), a multicenter, double-blind, randomized, placebo-controlled trial which enrolled patients with locally recurrent unresectable or metastatic TNBC. To be eligible for the study, participants had to have not been previously treated with chemotherapy in the metastatic setting. In a 2:1 ratio, patients were randomized to receive either 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.
Median progression-free survival was higher in the pembrolizumab arm compared with the placebo arm (9.7 months vs 5.6 months). Treatment-related adverse events with an incidence of greater than 20% in patients who received pembrolizumab included fatigue, nausea, diarrhea, constipation, vomiting, alopecia, rash, cough, decreased appetite, and headache. Common laboratory abnormalities included anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, elevated ALT and AST, hyperglycemia, hypoalbuminemia, increased alkaline phosphatase, hypocalcemia, hyponatremia, hypophosphatemia, and hypokalemia.
The 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 before chemotherapy until disease progression, unacceptable toxicity, or up to 24 months. The recommended chemotherapy dose to be administered with pembrolizumab includes 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 1,000 mg/m2 plus carboplatin AUC 2 mg/mL/min on days 1 and 8 every 21 days.
For More Information
Clinicaltrials.gov (2020). Study of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (MK-3475-355/KEYNOTE-335). NLM Identifier: NCT02819518.
Cortes J, Guo Z, Karantza V, et al (2018). KEYNOTE-355: randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (PBO) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC). J Clin Oncol, 36(suppl_5). DOI:10.1200/JCO.2018.36.5_suppl.TPS18