CDK4/6 inhibitors vs. weekly paclitaxel for ER+/HER2- advanced breast cancer with impending or established visceral crisis
In this paper, we report the results of our retrospective study from a large tertiary UK cancer centre of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) compared to weekly paclitaxel for treatment of estrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC) with visceral crisis (VC) or impending VC (IVC).
The ESO-ESMO international ABC guidelines [1] recommend ‘rapidly efficacious’ treatment for ER+/HER2- ABC with IVC/VC. Chemotherapy is frequently used instead of CDK4/6i based on the assumption it may be more rapidly efficacious. Prior to this paper, there had been little published evidence to confirm which treatment produces superior outcomes in IVC/VC. Recently presented results from the phase II randomised RIGHT Choice trial [2] have reported improved progression-free survival in pre/perimenopausal patients with ‘aggressive’ ER+/HER2− ABC receiving ribociclib + ET compared to combination chemotherapy. 52% of patients were reported to have VC, although their criteria for identifying VC has not yet been published.
In our study, over 1000 patients who had received treatment with a CDK4/6i or weekly paclitaxel between March 2017 and June 2021 at The Christie NHS Foundation Trust, UK were retrospectively identified from hospital electronic records. Records were manually screened to identify patients with ER+/HER2- ABC who had received first line treatment. Objective criteria for identifying patients with IVC/VC of the liver, lungs/mediastinum, gastrointestinal tract and/or bone marrow were defined based on the descriptive definitions of VC and IVC in the ESO-ESMO ABC guidelines. Patients were excluded if they had received previous CDK4/6i or any other systemic therapy for ABC, but previous single-agent ET for ABC was allowed in the paclitaxel cohort. On completion of screening, 27 patients in the CDK4/6i cohort and 32 patients in the paclitaxel cohort met criteria for inclusion.
All outcome measures including median time to treatment failure, progression-free survival and overall survival were significantly better in patients treated with CDK4/6i compared to paclitaxel. The median time to first improvement in IVC/VC was not significantly different in the CDK4/6i and paclitaxel cohorts.
The main limitations of this study are related to its retrospective nature. Although the cohorts were well balanced for most demographic and disease parameters, the paclitaxel cohort had more patients with ET-resistance, recurrent disease, VC and worse performance status. However, in multivariate analysis which included these characteristics as covariables, treatment with CDK4/6i was independently predictive of a longer progression-free survival.
Overall, this study showed that patients with ER+/HER2- ABC and IVC/VC treated with a CDK4/6i + ET had significantly better outcomes and a similar time to improvement in IVC/VC compared to patients treated with weekly paclitaxel. This is in agreement with the presented results from the RIGHT Choice trial. Therefore, CDK4/6i + ET should be considered as the preferred first line treatment option for patients with IVC/VC, rather than chemotherapy.
References:
- Cardoso, F.; Paluch-Shimon, S.; Senkus, E.; Curigliano, G.; Aapro, M.S.; André, F.; Barrios, C.H.; Bergh, J.; Bhattacharyya, G.S.; Biganzoli, L.; et al. 5th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 5). Annals of Oncology 2020, 31, 1623–1649, doi:10.1016/j.annonc.2020.09.010.
- Lu, Y.-S.; Mahidin, E.I.B.M.; Azim, H.; Eralp, Y.; Yap, Y.-S.; Im, S.-A.; Rihani, J.; Bowles, J.; Alfaro, T.D.; Wu, J.; et al. Abstract GS1-10: Primary Results from the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients with Aggressive HR+/HER2− Advanced Breast Cancer Treated with Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy. Cancer Research 2023, 83, GS1-10, doi:10.1158/1538-7445.SABCS22-GS1-10.
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