Pyrotinib or Lapatinib Combined With Capecitabine in HER2–Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study

Abstract

PURPOSE Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P < .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.

Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis

“…Pyrotinib and neratinib are both irreversible ErbB receptor TKIs, which are different in nature from lapatinib, a reversible HER1 and HER2 receptor TKI. Both pyrotinib and neratinib were found to have superior efficacy than lapatinib [5,6]. The median PFS of 11.1 months in PHENIX study achieved by pyrotinib plus capecitabine is comparable to that of 8.8 months achieved by neratinib plus capetabine as third or later line therapy in NALA trial and that of 12.9 months achieved by neratinib plus paclitaxel as first-line treatment in the NEfERT-T trial [6,7], suggesting the potentially comparable efficacy of pyrotinib to neratinib.…”

“…Recently pyrotinib, a novel oral pan-ErbB receptor tyrosine kinase inhibitor (TKI), has shown very promising results in metastatic HER2-positive BC [2][3][4][5]. In a phase II study, pyrotinib plus capecitabine had significantly higher objective response rate (ORR) (78.5% vs. 57.1%, p=0.01) and longer progression-free survival (PFS; 18.1 months vs. 7.0 months, p < 0.001) compared to lapatinib plus capecitabine [5].…”

“…Recently pyrotinib, a novel oral pan-ErbB receptor tyrosine kinase inhibitor (TKI), has shown very promising results in metastatic HER2-positive BC [2][3][4][5]. In a phase II study, pyrotinib plus capecitabine had significantly higher objective response rate (ORR) (78.5% vs. 57.1%, p=0.01) and longer progression-free survival (PFS; 18.1 months vs. 7.0 months, p < 0.001) compared to lapatinib plus capecitabine [5]. Recently, PHENIX study, a double-blinded, multicenter, randomized phase III study, showed that pyrotinib plus capecitabine significantly prolonged PFS (11.1 months vs. 4.1 months, p < 0.001) and increased ORR (68.6% vs. 16.0%, p < 0.001) than capetabine monotherapy [2].…”

Pyrotinib sensitizes 5‑fluorouracil‑resistant HER2-positive breast cancer cells to 5‑fluorouracil

“…Developing combination treatment of targeted therapies with cytotoxic agents is critical strategy for HER2 + breast cancer. Some studies showed that combination pyrotinib with capecitabine significantly improved PFS and ORR in patients with HER2 + metastatic breast cancer [11,12]. These results revealed the synergistic anticancer activities of pyrotinib plus capecitabine against HER2 + breast cancers.…”

Risk and prognostic factors of breast cancer with liver metastases

“…The gene that encodes HER2 is ampli ed and overexpressed in 15-20% of newly diagnosed breast cancer and results in a worse survival [38,39]. Nevertheless, diverse HER2-directed drugs have signi cantly improved survival in breast cancer patients with HER2-positive subtype [40][41][42][43][44][45]. Even for HER2 positive metastatic breast cancer, anti HER2 therapy also results in considerable and long-lasting improvement in quality of life and overall survival [46].…”