23P CDK4/6 inhibition and endocrine therapy (ET) in the HER2-enriched subtype (HER2-E) in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (ABC): A retrospective analysis of real-world data

e13035 Background: CDK 4/6 inhibitors plus hormone therapy(HT) has been approved by FDA and EMA for the treatment of hormone receptor positive HER2 negative advanced breast cancer (HR+/HER2-BC) with improvement in PFS consistently demonstrated in several clinical trials. Benefit in OS has also been demonstrated in Monaleesa3 and Monarch2 clinical trials. To date we don`t have real-world data and no single biomarker has been validated to identify subgroups that would benefit most from this new drugs. Methods: This is a multicenter, real life, observational study. From January 2015 to December 2019 we recruited 98 patients with immunohistochemical(IHC) HR+/HER2-BC treated with CDK4-6 inhibitor plus HT. All patients were classified into intrinsic molecular subtypes based on PAM50 signature done centrally in diagnostic/metastatic biopsies. Results: The clinical and treatment characteristic are in table. In IHC studies all population were classified as luminalA (40%) and LuminalB (60%) but we found HER2 enriched patients (6%) defined by PAM50. The median PFS for all population was 14 months and median PFS for Luminal A subtype was 12 months and 15 months for Luminal B with no statistically significant differences between them. Conclusions: Based on the results obtained, the intrinsic molecular subtype defined by PAM50 does not appear to be associated with differences in PFS in our study group. However, a study with a larger number of patients would be necessary. Inhibitors of CDK4/6, have established a central role in the management of HR+/HER2-BC. There is a clear benefit in PFS and OS but we still don’t know which patients will benefit from this therapy and who will not while the side effects such chronic neutropenia, QTC prolongation and diarrhea could have a negative impact on their quality of life. Its mandatory to explore a good biomarker to direct therapy. [Table: see text]

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Optimal duration of prior endocrine therapy predicts the efficacy of Fulvestrant in a real‐world study for patients with hormone receptor‐positive and HER2‐negative advanced breast cancer

Cancer Medicine ◽

10.1002/cam4.3491 ◽

2020 ◽

Vol 9 (23) ◽

pp. 8821-8831

Author(s):

Yannan Zhao ◽

Yi Li ◽

Chengcheng Gong ◽

Yizhao Xie ◽

Jian Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Real World ◽

Hormone Receptor ◽

Advanced Breast ◽

Hormone Receptor Positive ◽

Optimal Duration

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Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: A Nation-Wide Multicenter Epidemiological Study in China

Frontiers in Oncology ◽

10.3389/fonc.2020.599604 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yun Wu ◽

Yiqun Han ◽

Pei Yu ◽

Quchang Ouyang ◽

Min Yan ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Practice ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Real World ◽

Hormone Receptor ◽

Treatment Patterns ◽

Advanced Breast ◽

First Line ◽

Hormone Receptor Positive

BackgroundClinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.MethodsUsing data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.ResultsA total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.ConclusionsLess than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.

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Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13017 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13017-e13017

Author(s):

Inês Moreira ◽

Marta Ferreira ◽

Ana Afonso ◽

Ana Ferreira ◽

Ana Rodrigues ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Overall Response Rate ◽

Response Rate ◽

Advanced Breast ◽

Overall Response ◽

Hormone Receptor Positive

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

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