Purpose: Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2+ ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC in real-world setting. Patients and Methods: In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Results: Up to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0-1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2-4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%). Conclusion:This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC.

Based on the well‐known cytotoxicity of indole compounds, we used the ‘Fisher indole synthesis’ method to introduce appropriately substituted indole rings into panaxadiol (PD), generating eighteen novel Panaxadiol indole derivatives. Six human cancer cell lines (A549, HepG‐2, HCT‐116, SGC‐7901, MDA‐MB‐231, PC‐3 cells) and one normal ovarian cell lines (IOSE144) were designed to evaluate the anti‐proliferative activity of the PD derivatives. The results showed that the majority of PD derivatives showed enhanced anti‐proliferative activity, when compared with PD, with P‐Methylindolo‐PD exhibiting the highest cytotoxicity. In A549 cells, IC50 value was 5.01±0.87 μM, which is roughly 12 times higher than the activity of PD and 5 times that of 5‐FU. Moreover, cell morphology analysis and Annexin V‐FITC/PI assays exhibited that P‐Methylindolo‐PD could induce A549 cell apoptosis (55.7 % of apoptotic cells at 20 μM). Moreover, molecular docking experiments were performed to explore the molecular mechanism underlining the binding of P‐Methylindolo‐PD to the active site of EGFR. The results support that P‐Methylindolo‐PD might be a promising lead compound for further studies.