The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

For women with trastuzumab-pretreated metastatic breast cancer, median progression-free survival (PFS) was prolonged by a factor of 2.7 with the addition of pyrotinib, an oral panHER tyrosine kinase inhibitor, to capecitabine compared with placebo plus capecitabine, according to results of the phase 3 PHENIX trial ( Identifier: NCT02973737), which were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Previous results from early-phase trials have shown pyrotinib — an orally administered, irreversible tyrosine kinase inhibitor that targets both HER1 (ie, EGFR) and HER2 — to be well tolerated, with promising antitumor activity in patients with HER2-positive metastatic breast cancer.2

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In this placebo-controlled, double-blind, multicenter, randomized phase 3 trial, Chinese patients with HER2-positive metastatic breast cancer were randomly assigned in a 2:1 ratio to receive either pyrotinib (400 mg) or placebo in combination with capecitabine. All enrolled patients had previously been treated with an anthracycline, a taxane, and trastuzumab in either the adjuvant or metastatic settings and were not eligible to receive lapatinib or additional trastuzumab. Patients who were previously treated with lapatinib, neratinib, pyrotinib or any other HER2-targeted tyrosine kinase inhibitor, or capecitabine, were excluded from the study.

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The primary study end point of PFS was assessed in all patients receiving at least 1 dose of study medication. Patients with disease progression on placebo plus capecitabine could receive treatment with pyrotinib monotherapy. Objective response rate (ORR) was a secondary study end point.

Of the 279 patients randomly assigned to a treatment arm, 185 and 94 received pyrotinib plus capecitabine and placebo plus capecitabine, respectively. Median PFS for patients treated with pyrotinb plus capecitabine was 11.1 months compared with 4.1 months for those receiving placebo plus capecitabine (hazard ratio [HR], 0.18; 95% CI, 0.13-0.26; P <.001). The ORRs for patients treated with pyrotinib plus capecitabine and placebo plus capecitabine were 68.6% and 16.0%, respectively, with a median PFS of 5.5 months and an ORR of 38.0% for patients from the placebo arm subsequently treated with pyrotinib.

Higher adverse event rates were observed for patients receiving the pyrotinib-containing regimen, with diarrhea (30.8% vs 12.8% [placebo plus capecitabine]) and hand-foot syndrome (15.7% vs 5.3%), as the most common grade 3 or higher adverse events.

In summarizing the results of this study, presenter Zefei Jiang, MD, of the Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China, stated that “pyrotinib plus capecitabine significantly improved median PFS versus placebo plus capecitabine in women with HER2-positive metastatic breast cancer after treatment with trastuzumab and taxanes.”

In reviewing the design and results of this study, the discussant, Carlos Barrios, MD, director, Instituto do Câncer, Hospital Mãe de Deus, Porto Alegre, Brazil, noted that “the comparator is not a standard second-line regimen [in this patient population].”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.


  1. Jiang Z, Yan M, Hu X, et al. Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: A randomized phase III study. Presented at: 2019 American Association of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 1001.
  2. Ma FLi QChen S, et al. Phase I study and biomarker analysis of pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2017;35(27):3105-3112.