Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041)

Eur J Cancer. 2023 May:184:1-9. doi: 10.1016/j.ejca.2023.01.001. Epub 2023 Jan 9.

Abstract

Background: Pembrolizumab is approved for the neoadjuvant/adjuvant treatment of early triple-negative breast cancer (TNBC) patients in combination with chemotherapy. The Keynote-522 trial used platinum chemotherapy. As neoadjuvant nab-paclitaxel (nP) is also highly effective in triple-negative breast cancer patients, this study investigates the response to nP-containing neoadjuvant chemotherapy in combination with pembrolizumab.

Patients and methods: NeoImmunoboost (AGO-B-041/NCT03289819) is a multicenter, prospective single-arm phase II trial. Patients were treated with 12 weekly cycles of nP followed by four three-weekly cycles of epirubicin/cyclophosphamide. Pembrolizumab was given three-weekly in combination with these chemotherapies. The study was planned for 50 patients. After 25 patients, the study was amended to include a pre-chemotherapy single application of pembrolizumab. The primary aim was pathological complete response (pCR), and the secondary aims were safety and quality of life.

Results: Of 50 included patients, 33 (66.0%; 95%confidence interval: 51.2%-78.8%) had a (ypT0/is ypN0) pCR. The pCR rate in the per-protocol population (n = 39) was 71.8% (95%confidence interval: 55.1%-85.0%). The most common adverse events of any grade were fatigue (58.5%), peripheral sensory neuropathy (54.7%) and neutropenia (52.8%). The pCR rate in the cohort of 27 patients with a pre-chemotherapy pembrolizumab dose was 59.3%, and 73.9% in the 23 patients without pre-chemotherapy dose.

Conclusions: pCR rates after NACT with nP and anthracycline combined with pembrolizumab are encouraging. With acceptable side-effect profiles, this treatment might be a reasonable alternative to platinum-containing chemotherapy in cases of contraindications. However, without data from randomised trials and long-term follow up, platinum/anthracycline/taxane-based chemotherapy remains the standard combination chemotherapy for pembrolizumab.

Keywords: Neoadjuvant chemotherapy; PD-L1; Pembrolizumab; Triple-negative.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracyclines
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / drug therapy
  • Cyclophosphamide
  • Epirubicin
  • Female
  • Humans
  • Neoadjuvant Therapy / methods
  • Paclitaxel
  • Platinum / therapeutic use
  • Prospective Studies
  • Quality of Life
  • Treatment Outcome
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • 130-nm albumin-bound paclitaxel
  • pembrolizumab
  • Platinum
  • Cyclophosphamide
  • Paclitaxel
  • Anthracyclines
  • Epirubicin