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Combining pyrotinib with capecitabine reduced the risk of disease progression or death by 64% compared with lapatinib (Tykerb) plus capecitabine in Chinese patients with relapsed or metastatic HER2-positive breast cancer.
Combining the irreversible pan-ErbB inhibitor pyrotinib with capecitabine reduced the risk of disease progression or death by 64% compared with lapatinib (Tykerb) plus capecitabine in Chinese patients with relapsed or metastatic HER2-positive breast cancer who previously received taxanes, anthracyclines, and/or trastuzumab (Herceptin), according to data from a phase II study published in the Journal of Clinical Oncology.
The median progression-free survival (PFS) was 18.1 months (95% CI, 13.9 to not reached) in the pyrotinib arm compared with 7.0 months (95% CI, 5.6-9.8) in the lapatinib arm (adjusted HR, 0.36; 95% CI, 0.23 to 0.58; P <.001). The overall response rates (ORRs) were 78.5% (95% CI, 68.5%-88.5%) versus 57.1% (95% CI, 44.9%-69.4%), respectively (P = .01).
“The outcomes of this study are consistent with those in a single-center, open-label phase I study of pyrotinib in patients with HER2-positive metastatic breast cancer. On the strength of the findings of this phase II trial, a phase III trial (NCT03080805) is being conducted to evaluate the efficacy and safety of pyrotinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive breast cancer who have previously been treated with trastuzumab and taxanes,” wrote first author Fei Ma, MD, and coinvestigators.
The phase II study (NCT02422199) included 128 patients accrued between May 29, 2015, and March 15, 2016, at 11 hospitals in China. Patients characteristics were well balanced between the study arms. Overall, the median age was 48 years (range, 25-70), and all patients had an ECOG performance status of 0 or 1. The majority (62.5%) of patients had hormone receptor—positive disease and 76.6% had visceral disease.
Patients in the pyrotinib arm had received a median of 20 (range, 2-30) prior treatment cycles compared with 10 (range, 2-28) in the lapatinib cohort. Across both arms, 53.9% had prior trastuzumab; however, no patients had been treated with pertuzumab (Perjeta) or ado-trastuzumab emtansine (Kadcyla).
Patients were randomized in a 1:1 ratio to receive capecitabine at 1000 mg/m2 orally twice per day on days 1 to 14 of 21-days cycles combined with either oral pyrotinib (400 mg daily for 21 days; n = 65) or oral lapatinib (1250 mg daily for 21 days; n = 63). Patients were treated until disease progression, unacceptable toxicity, withdrawal of consent, or withdrawal by the investigator. The primary endpoint was ORR (RECIST, version 1.1) per investigator assessment.
The 78.5% (n = 51) ORR in the pyrotinib arm comprised 3 complete responses (CRs) and 48 partial responses (PRs). Fourteen patients had stable disease and no patients had progressive disease. The median time to progression was 19.5 months and the median duration of response was 16.7 months (95% CI, 12.5 to not reached).
Among patients receiving lapatinib, the 57.1% ORR (n = 36) included 1 CR and 35 PRs. Twenty-two patients had stable disease and 5 patients had progressive disease. The median time to progression was 7.0 months and the median duration of response was 8.4 months (range, 4.7-13.8).
Regarding toxicity, the most common grade 3/4 adverse events with pyrotinib versus lapatinib, respectively, were hand-foot syndrome (24.6% vs 20.6%), diarrhea (15.4% vs 4.8%), and decreased neutrophil count (9.2% vs 3.2%).
Noting the limitations of the study and next steps, Ma et al wrote, “A study limitation was that centralized review of HER2 status was not undertaken. All the participants were Chinese; additional studies in other races will be required to confirm pyrotinib efficacy in these populations.”
Ma F, Ouyang Q, Li W, et al. Pyrotinib or lapatinib combined with capecitabine in HER2-positive metastatic breast cancer with prior taxanes, anthracyclines, and/or trastuzumab: a randomized, phase II study (published online August 20, 2019). J Clin Oncol. doi: 10.1200/JCO.19.00108.