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). (May 2023)

• Record Type: Journal Article
• Authors: Fasching, Peter A.; Hein, Alexander; Kolberg, Hans-Christian; Häberle, Lothar; Uhrig, Sabrina; Rübner, Matthias; Belleville, Erik; Hack, Carolin C.; Fehm, Tanja N.; Janni, Wolfang; Hartmann, Arndt; Erber, Ramona; Theuser, Anna-Katharin; Brucker, Sara Y.; Hartkopf, Andreas D.; Untch, Michael
• Is Part Of: European journal of cancer. Volume 184(2023)
• Page Start: 1
• Page End: 9
• Publication Date: 2023-05
• Subjects: Neoadjuvant chemotherapy -- Pembrolizumab -- Triple-negative -- PD-L1; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2023.01.001
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: Neoadjuvant nab-paclitaxel(nP)/anthracycline + pembrolizumab shows a pathological complete response rate of 66%. A pre-chemotherapy pembrolizumab (pembro) dose did not indicate different pathological complete response rates. If platinum is contraindicated nab-paclitaxel could be an alternative to combine with pembro.