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Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy?

ABSTRACT: Based on the findings of modern molecular biology, breast cancer is nowadays considered to be a heterogeneous disease. This leads to the objective of an individualised, more patient-oriented therapy. A series of target molecules for this purpose has already been identified. The principle of targeted oncological therapy was realised decades ago with the introduction of endocrine therapy for patients with hormone receptor-positive tumours. The modern therapy for HER2-positive tumours is a further example for the translation of targeted therapy into clinical routine. For patients with HER2-negative metastatic breast cancer, to date two targeted drugs, bevacizumab and everolimus, are available for routine clinical use. Many other substances are still undergoing clinical development. However, validated predictive markers to aid in therapeutic decision-making and therapy control are still lacking. Chemotherapy constitutes an effective palliative therapy with proven efficacy for the patients. In this process strategies have also been realised for a targeted therapy against tumour cells with the help of chemotherapeutic agents such as, for example, the intracellular activation of the prodrug capecitabine or the active albumin-mediated transport of nab-paclitaxel which leads to higher peri- and intratumoural enrichments. The continuing unchanged relevance of chemotherapy is often underestimated in the current discussions and will be comprehensively evaluated in this review.

SUBMITTER: Schneeweiss A

PROVIDER: S-EPMC4490921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2- breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i.MethodsRetrospective analysis of electronic health record-derived data for HR+ HER2- metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis.ResultsSix hundred twenty-two patients received EE first-line (n?=?104, 16.7%), second-line (n?=?273, 43.9%) or third-line (n?=?245, 39.4%). Median TTNT was 8.3?months, 5.5?months, and 4.8?months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2?months (95% CI 5.2, 7.3) vs 4.3?months (95% CI 3.2, 5.7) respectively, p?=?0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6?months (95% CI 4.4, 6.9) vs 4.1?months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p?=?0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7?months vs. 32.7?months (p?=?0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2?months vs. 40.8?months (p?<?0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy.ConclusionThis study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.

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Chemotherapy for Metastatic Breast Cancer - An Anachronism in the Era of Personalised and Targeted Oncological Therapy?

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