TNBC: novel targeted therapy does well in genetically sensitive patients

  • Bardia A & al.
  • J Clin Oncol
  • 20 Sep 2018

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

  • LCL161 is a targeted experimental therapy that induces tumor necrosis factor (TNF)-mediated apoptosis in models of triple-negative breast cancer (TNBC).
  • In this phase 2 trial, LCL161 enhanced the efficacy of paclitaxel in patients with TNBC with a TNF-based gene expression signature (GS), but not in patients without the signature.

Why this matters

  • Findings are promising enough to warrant progression to a phase 3 trial.

Study design

  • Randomized controlled phase 2 trial of 209 patients with localized TNBC (T2/N0-2/M0).
  • Patients were divided into GS-positive and GS-negative groups; each group was randomly assigned to oral LCL161 (1800 mg/week) and intravenous paclitaxel (80 mg/m2 once weekly; combination group) or paclitaxel alone (control group) for 12 weeks, followed by surgery.
  • Primary outcome: >7.5% increase in pathologic complete response (pCR) over control group.
  • Funding: Novartis.

Key results

  • GS-positive group: pCR rate was greater in the combination than the control group (38.2% vs 17.2%), with 88.8% posterior probability of >7.5% increase in pCR.
  • GS-negative group: pCR rate was lower in the combination group (5.6% vs 16.4%), with 0% posterior probability of >7.5% increase in pCR.
  • The combination group had higher rates of grades 3/4 neutropenia (24.5% vs 3.9%) and diarrhea (5.7% vs 1.0%).

Limitations

  • Blinding not specified.
  • No survival outcomes studied.

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