Among women with HER2+ metastatic breast cancer, treatment with pyrotinib plus capecitabine (Xeloda; Genentech) resulted in significantly better progression-free survival than did lapatinib (Tykerb; Novartis) plus capecitabine following treatment with trastuzumab (Herceptin; Genentech) and chemotherapy, new research has found.
Combination therapy with the irreversible pan-ErbB inhibitor pyrotinib and capecitabine also yielded manageable toxicity, the researchers added, which they said verified earlier findings with the agents.
Reporting in an abstract published online as part of the 2020 virtual meeting of the American Society of Clinical Oncology (abstract 1003), the team of Chinese investigators at the helm of the trial (NCT03080805) explained that previous phase I and II studies of pyrotinib plus capecitabine demonstrated clinically meaningful benefits and acceptable tolerability among patients with HER2+ metastatic breast cancer. The current investigation -- an open-label, multi-center, randomized phase-III study -- followed up on this previous work.
As part of the current trial -- headed by Binghe Xu, MD, PhD, Professor of Medical Oncology at Peking Union Medical College in Beijing, China -- 267 HER2+ metastatic breast cancer patients were enrolled following treatment with trastuzumab and taxanes, and/or anthracyclines. As many as two prior lines of chemotherapy for metastatic disease were allowed.
During the July 2017-October 2018 study period, the patients were randomly assigned to receive either once daily 400 mg pyrotinib (n=134) or 1250 mg lapatinib (n=133) continuously, plus twice-daily 1000 mg/m2 capecitabine on days 1-14 of the 21-day treatment cycles. The study’s primary endpoint was progression-free survival, as determined by blinded independent central review.
One patient (in the lapatinib arm) did not receive study treatment and was excluded from the final analysis. With respect to prior treatment, 42.5% of patients in the pyrotinib arm had no prior chemotherapy for metastatic disease, compared with 34.8% of their counterparts in the lapatinib arm. Similarly, 41.8% and 49.2%, respectively, had one prior chemotherapy line, while 15.7% and 15.9%, respectively, had two prior lines of chemotherapy.
At the planned interim analysis, it was found that the median progression-free survival was 12.5 months (95% confidence interval: 9.7 months-not reached) among patients who received pyrotinib plus capecitabine, compared with 6.8 months (95% CI: 5.4-8.1 months) for those who received lapatinib plus capecitabine (hazard ratio 0.39; p<0.0001). This, the researchers added, met the criterion for statistical significance, which was defined a priori as ≤0.0066.
Among trastuzumab-resistant patients, the researchers also observed prolonged progression-free survival with pyrotinib plus capecitabine (12.5 months; 95% CI: 6.9 months-not reached), compared with 6.9 months among women who received lapatinib plus capecitabine (95% CI: 5.4 months-not reached; HR 0.60).
As Table 1 indicates, patients treated with pyrotinib and capecitabine also demonstrated benefits with respect to objective response rate, clinical benefit rate, and duration of response.
Pyrotinib (n=134) | Lapatinib (n=133) | |
Objective response rate (%; 95% CI) | 67.2 (58.5-75.0) | 51.5 (42.7-60.3) |
Clinical benefit rate (%; 95% CI) | 73.1 (64.8-80.4) | 59.1 (50.2-67.6) |
Duration of response (median months; 95% CI) | 11.1 (9.7-not reached) | 7.0 (5.6-9.8) |
Ongoing response, n (%) | 63 (70.0) | 33 (48.5) |
The researchers noted a number of adverse events in the trial. Of these, the most common (at least grade 3) were diarrhea (30.6% pyrotinib; 8.3% lapatinib) and hand-foot syndrome (16.4% vs 15.2%).
These findings, the researchers concluded, confirm phase-II results, and demonstrate that pyrotinib plus capecitabine may be a viable treatment option for patients with HER2+ metastatic breast cancer after trastuzumab and chemotherapy.
The study was funded by Jiangsu Hengrui Medicine.
