Background: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. Patients and methods: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for !5 years AE abemaciclib for 2 years. Cohort 1 enrolled patients with !4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor !5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (!20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. Results: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib þ ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) ¼ 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P ¼ 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR ¼ 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR ¼ 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. Conclusion: Abemaciclib þ ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

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Sunitinib appears to be an active agent in this malignancy based on this limited cohort, with an understandable mechanism of action similar to that described in other hypoxia-driven tumors. A single arm phase 2 trial is underway.

1024 Background: The occurrence of changes in tumor receptor profile (ER, PR and HER-2/neu) between primary and metastatic tissue has been recognised and may have significant treatment implications. Previous reports on receptor discordance rates have tended to be from sub-studies of clinical trials. We sought to evaluate the degree of ER, PR and HER-2/neu receptor discordance in patients treated at two Canadian cancer centres. Methods: Archival data was collected on patients for whom tissue from both primary and metastatic sites was available. Patients with recurrences in the breast or axilla were excluded. ER, PR and HER-2/neu status in the primary and metastasis were compared. Additional information including adjuvant therapy and time to metastasis biopsy was gathered. Results: To date, data is available on 80 patients. Hormone receptor (HR) status was available for 96% of primaries and 56% of metastases. HR status on both the primary and the metastasis was performed in 51% of cases. The discordance rate for ER was 21% (2-sided p=0.0096). 12% of patients changed from ER+ to ER- and 9% changed from ER- to ER+. The discordance rate for PR was 37% (2-sided p=0.0001), with all of these patients changing from PR+ to PR-. No significant HR discordance was found among different adjuvant hormone therapy subgroups. There was no correlation between HR discordance and time to rebiopsy. No discordance for HER-2/neu was found. Conclusions: Significant discordance for HR status was observed, 21% for ER and 37% for PR. HER-2/neu discordance was not observed. We are currently exploring the practical implications of these discordance rates on the management of advanced breast cancer patients in a prospective trial. No significant financial relationships to disclose.