Pyrotinib in the first-line treatment of HER2-positive advanced breast cancer: Results from the PRETTY study.

e13016Background: Pyrotinib is an irreversible tyrosine kinase inhibitor that inhibits EGFR, HER2, and HER4. Multiple studies have demonstrated the efficacy and safety of pyrotinib in HER2-positive advanced breast cancer. The phase 3 PHILA study demonstrated that pyrotinib combined with trastuzumab and chemotherapy achieved promising efficacy in the first-line treatment of HER2-positive advanced breast cancer. Here we supplemented real-world evidence on first-line use of pyrotinib. Methods: The PRETTY study was a nationwide, prospective observational study conducted at 61 sites in China from August 2019 to November 2021, enrolling 1129 patients with HER2-positive advanced breast cancer treated with pyrotinib-based regimens. The primary outcome was real-world progression-free survival (rwPFS). This analysis focused on the effectiveness data of patients in the first-line group. Results: A total of 437 patients receiving first-line pyrotinib treatment were included, of whom 81 (18.5%) received pyrotinib-trastuzumab-based therapy and 356 (81.5%) received pyrotinib-based therapy without trastuzumab. Among them, 304 patients (69.6%) had previously been treated with trastuzumab, and 55 (12.6%) had received both trastuzumab and pertuzumab. In univariable analysis, patients with de novo disease (p < 0.001), visceral metastases (p < 0.001), brain metastases (p = 0.004), or a treatment-free interval from previous adjuvant therapy (TFI) ≥24 months (p = 0.003) were more likely to receive pyrotinib-trastuzumab based therapy. Multivariable logistic regression showed that patients with a TFI ≥24 months were more likely to receive pyrotinib-trastuzumab based therapy (odds ratio: 0.32, 95% CI, 0.13-0.77, p = 0.01), while trastuzumab-treated patients were more likely to receive pyrotinib-based therapy (odds ratio: 2.62, 95% CI, 1.28-5.37, p = 0.008). By the data cutoff date on May 29, 2022, the median follow-up duration was 11.8 (IQR, 7.2-16.9) months, the median rwPFS for the overall first-line population was 17.8 months (95% CI, 15.2-24.9). The rwPFS was not reached (NR) (95% CI, NR-NR) with pyrotinib-trastuzumab based therapy and 17.8 months (95% CI, 14.5-21.2) with pyrotinib-based therapy. In trastuzumab-treated patients, the median rwPFS was 19.9 months (95% CI, 17.1-22.7), and in trastuzumab-pertuzumab-treated patients, the median rwPFS was 24.9 months (95% CI, NR-NR). Conclusions: In real world, patients who received first-line pyrotinib-trastuzumab-based regimens achieved favorable effectiveness. With the continuous development of anti-HER2 therapy in the early stage, further exploration of pyrotinib-based regimens in the first-line treatment of HER2-positive advanced breast cancer is warranted. Clinical trial information: NCT04158505.