FDA grants pembrolizumab accelerated approval for advanced TNBC

  • US Food and Drug Administration

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • Pembrolizumab received accelerated approval by the FDA for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC).
  • Tumors must express the protein PD-L1 using an FDA-approved test.
  • Approval was based on the KEYNOTE-355 trial showing that the pembrolizumab+chemo group lived an additional 4.1 months.

Why this matters

  • TNBC has the highest mortality among breast cancer subtypes.
  • Pembrolizumab is 1 of the first immunotherapies approved for any breast cancer subtype.

Key points

  • Tumors expressing PD-L1 must have a combined positive score ≥10.
  • Pembrolizumab must be given in combination with chemotherapy.
    • Pembrolizumab's recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks before chemotherapy until disease progression or unacceptable toxicity or up to 24 months.
    • Chemotherapy must be 1 of 3 regimens: paclitaxel protein-bound, paclitaxel, or gemcitabine by intravenous infusion.
  • Highlights of KEYNOTE-355:
    • Multicenter, double-blind, randomized, placebo-controlled trial in locally recurrent unresectable or metastatic TNBC not already treated with chemotherapy.
    • Primary outcome:
      • PFS was 9.7 months in the pembrolizumab+chemo group vs 5.6 months in the placebo+chemo group. 
      • HR, 0.65 (one-sided P=.0012).
    • Most common adverse events (incidence ≥20%) with pembrolizumab+chemo group were fatigue, nausea, diarrhea, constipation, vomiting, alopecia, among others.
    • Most common laboratory abnormalities were anemia, leukopenia, neutropenia, among others.