The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2- negative (HER2-) metastatic breast cancer (MBC).

Abstract

1056 Background: Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2- MBC. When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. We hypothesized that clinicopathological baseline and prior ET factors determine chemotherapy’s efficacy. We sought to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC. Methods: We conducted a retrospective study of patients with HR+/HER2- MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999-2017. We collected baseline clinicopathological and all treatment data. The primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC. We performed univariate and multivariate analyses using the Cox proportional hazard model. Kaplan-Meier methods were used to analyze TTF. Results: In the 1,258 patients analyzed, the mean age was 55.3 years (range 21-91). Forty-five patients (3.6%) had inflammatory breast cancer (IBC). Three hundred ninety patients (31%) received previous targeted therapy: 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (paclitaxel, nab-paclitaxel, or docetaxel; 28.6%). After adjustment for all factors in a multivariate model, IBC and prior exposure to a CDK4/6 inhibitor were significantly associated with shorter TTF. Previous treatment with a CDK4/6 inhibitor had the strongest negative effect on chemotherapy TTF regardless of ET duration (adjusted hazard ratio [HR] 1.84; 95%CI 1.49-2.27; p < 0.001). Capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in (neo)adjuvant setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55-0.75; p < 0.001). Conversely, the median TTF for taxanes was shorter in patients who received prior (neo)adjuvant taxanes than in those who did not (4.5 vs 5.1 months). Conclusions: Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.