medwireNews: Combining pyrotinib instead of lapatinib with capecitabine is associated with significantly improved progression-free survival (PFS) in patients who have received prior treatment for HER2-positive metastatic breast cancer, show phase 3 trial data.
These findings, presented at the virtual 2020 ASCO Annual Meeting, confirm those from the randomized phase 2 study in the same patient population, said Binghe Xu (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing).
He added that the combination of the pan-ErbB tyrosine kinase inhibitor and capecitabine has been approved for the second-line treatment of HER2-postive metastatic breast cancer patients in China.
The PHOEBE trial enrolled patients who had already received treatment with trastuzumab and taxanes, with or without anthracyclines, and up to two lines of chemotherapy for metastatic disease (median, 1). Participants were randomly assigned to receive pyrotinib 400 mg/day (n=134) or lapatinib 1250 mg/day (n=132), both given alongside capecitabine 1000 mg/m2 twice a day on days 1–14 of every 21-day cycle.
At a median follow-up of 9.9 months, the primary endpoint of PFS by independent review was significantly improved with pyrotinib versus lapatinib, at a median of 12.5 and 6.8 months, respectively, giving a hazard ratio of 0.39 in favor of pyrotinib.
Pyrotinib was favored across all subgroups, although the PFS benefit did not reach statistical significance for some subgroups, such as patients with trastuzumab resistance (defined as relapse within 6 months of adjuvant use and/or within 3 months in the metastatic setting) and those with non-visceral metastases.
The objective response rate was higher in the pyrotinib than lapatinib treatment arm, at 67.2% versus 51.5% (complete responses in 5.2 vs 0.8%), as was the clinical benefit rate, at 73.1% versus 59.1%. The median durations of response were 11.1 and 7.0 months, respectively, and a corresponding 70.0% and 48.5% of responses were ongoing at data cutoff.
Overall survival (OS) data had not reached maturity, “but we observed a clear trend in OS benefit with pyrotinib combined treatment,” said Xu reporting 1-year OS rates of 91.3% and 77.4% among pyrotinib- and lapatinib-treated participants, respectively.
Treatment-related adverse events (TRAEs) of at least grade 3 occurred in 57.5% of patients who received pyrotinib and 34.1% of those given lapatinib. Diarrhea was the most common TRAE of this grade in the pyrotinib arm, observed at a rate of 30.6% compared with 8.3% in the lapatinib arm, but it seldom led to treatment discontinuation, highlighted Xu.
A total of 47.0% of patients in the pyrotinib group required dose modification due to AEs, 61.9% needed a treatment interruption, and 3.0% discontinued one or both drugs. The corresponding rates in the lapatinib group were 33.3%, 48.5%, and 2.3%.
No deaths were attributed to TRAEs in the pyrotinib study arm, but there was one such death in the lapatinib arm.
Discussant Aleix Prat, from Hospital Clínic de Barcelona in Spain, commented that “pyrotinib is a new pan-HER inhibitor with clinical value” shown across two phase 3 clinical trials.
But he added that “its value in the setting of pertuzumab, T-DM1, tucatinib, DS-8201 and neratinib is less clear,” and “the toxicity profile needs attention.”
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