Neoadjuvant pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide for HER2-positive locally advanced breast cancer: a retrospective case-series study

Abstract

Background: The anti-tumor activity of pyrotinib has been confirmed in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study investigated the effect of pyrotinib plus nabpaclitaxel, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with HER2-positive locally advanced breast cancer.Methods: In this single-center retrospective study, female patients with HER2-positive locally advanced breast cancer received pyrotinib 320 mg orally once a day and the TAC regimen (nab-paclitaxel 260 mg/m 2 , liposomal doxorubicin 20 mg/m 2 , and cyclophosphamide 600 mg/m 2 ) on day 1 of each 21-day cycle. Surgery was performed after 4-6 cycles of neoadjuvant therapy. The outcomes included total pathological complete response (tpCR, ypT0/Tis ypN0) rate, objective response rate (ORR) after neoadjuvant therapy, progressionfree survival, overall survival, and the incidence of adverse events (AEs).Results: Between March 2019 and January 2020, a total of 22 patients were included. The median age was 48 years (range, 32-60). The ORR was 100% after the completion of neoadjuvant therapy. Ten (45.5%) patients achieved tpCR, including four of ten (40.0%) patients with positive hormone receptor, and six of 12 (50.0%) patients with negative hormone receptor. As at December 2020, no disease recurrence, progression, or death occurred. All patients suffered AEs after neoadjuvant therapy, most of which were grade 1-2. Grade ≥3 AEs included diarrhea [4 (18.2%)], rash [2 (9.1%)], and hand-foot syndrome [1 (4.5%)]. Conclusions: Neoadjuvant pyrotinib combined with the TAC regimen showed promising clinical benefit in patients with HER2-positive locally advanced breast cancer, with an acceptable safety profile.

Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: A systematic review and meta‑analysis

“…Consequently, up to 96% of patients with diarrhea treated with second-generation TKIs are assumed to have direct mucosal atrophy and injury caused by the inhibition of ErbB signaling within the intestinal epithelia (32,33). The results from the analysis of the present study revealed that gastrointestinal reactions, as well as myelosuppression, are the most common adverse events of any Grade and also Grade ≥3, which was consistent with other retrospective studies (34)(35)(36)(37). It is worth noting that nearly half of the participants in the present analysis experienced Grade 3 diarrhea, with a significantly higher incidence compared with capecitabine combination therapy in advanced or metastatic breast cancer.…”

“…Overall, 207 out of 395 patients who received pyrotinib-containing neoadjuvant therapy achieved pCR (defined as the proportion of patients who achieved a complete response or partial response), and the objective response rate was close to 100% across all five studies. Real-world studies have confirmed the activity of pyrotinib in the neoadjuvant setting (34)(35)(36)(37). Owing to discrepancies in inclusion criteria, drug dosage and duration of therapy, optimal dosing of pyrotinib in combination with chemotherapy remains unknown and must be further explored in future research.…”

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial

“…As expected, pyrotinib-related diarrhea was the most frequent AE, whereas the overall safety profile in the present study was acceptable. The incidence of grade ≥3 diarrhea in this study was much lower than that of previously reported pyrotinib-containing neoadjuvant therapy (6.5% vs. 18.2–64.5%) ( 13 - 15 , 29 ). The use of a single HER2-targeted agent and a single chemo-drug in the neoadjuvant setting might have contributed to the low incidence of severe diarrhea.…”

“…Recently, various combinations of pyrotinib plus chemotherapy for HER2 + BC in the neoadjuvant setting have been increasingly explored. Several phase II trials showed that dual-target therapy with trastuzumab and pyrotinib plus neoadjuvant chemotherapy (NAC) exhibited pCR rates between 51.6% and 73.7% ( 13 , 15 , 29 , 30 ). A real-world analysis found that the tpCR rate of pyrotinib-containing neoadjuvant therapy was 48.5%, respectively ( 28 ).…”

Establishment and verification of a nomogram to predict tumor-specific mortality risk in triple-negative breast cancer: a competing risk model based on the SEER cohort study

“…Studies have presented that receiving radiotherapy and chemotherapy after surgery has significant clinical value in improving the prognosis of patients ( 26 , 44 ). Recently, neo-adjuvant chemotherapy has gradually become the first choice of systemic therapy for TNBC, especially for those who have locally advanced tumors ( 45 , 46 ). Neoadjuvant chemotherapy remarkably has been shown to improve the prognosis of the patients who received neo-adjuvant chemotherapy before surgery and achieved pathologic complete response during surgery ( 47 ).…”