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)
Mené sur 50 patientes atteintes d'un cancer du sein triple négatif de stade précoce, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité d'un traitement néoadjuvant combinant chimiothérapie et pembrolizumab
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 TNBC 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 pCR, and the secondary aims were safety and quality of life. Results : Of 50 included patients 33 (66.0%; 95%CI: 51.2%–78.8%) had a (ypT0/is ypN0) pCR. The pCR rate in the per-protocol population (n=39) was 71.8% (95%CI: 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 randomized trials and long term follow up, platinum/anthracycline/taxane based chemotherapy remains the standard combination chemotherapy for pembrolizumab.