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. 2023 Nov;202(1):83-95.
doi: 10.1007/s10549-023-07035-6. Epub 2023 Aug 16.

CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2- advanced breast cancer with impending or established visceral crisis

Roya Behrouzi  1 , Anne C Armstrong  2 , Sacha J Howell  2   3
Affiliations

CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2- advanced breast cancer with impending or established visceral crisis

Roya Behrouzi et al. Breast Cancer Res Treat. 2023 Nov.

Abstract

Purpose: ER+/HER2- advanced breast cancer (ABC) with visceral crisis (VC) or impending VC (IVC) is commonly treated with chemotherapy instead of CDK4/6 inhibitors (CDK4/6i). However, there is little evidence to confirm which treatment is superior. This study compared outcomes of patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i or weekly paclitaxel.

Methods: Patients with ER+/HER2- ABC receiving first line treatment at a large tertiary UK cancer centre from 1-Mar-2017 to 30-Jun-2021 were retrospectively identified. Hospital records were screened for IVC/VC affecting the liver, lungs/mediastinum, gastrointestinal tract and/or bone marrow. Baseline demographics, clinical data and survival outcomes were recorded up to 30-Jul-2022.

Results: 27/396 (6.8%) patients with ABC who received CDK4/6i and 32/86 (37.2%) who received paclitaxel had IVC/VC. Median time to treatment failure (TTF), progression-free survival (PFS) and overall survival (OS) were significantly longer in the CDK4/6i compared to paclitaxel cohort: TTF 17.3 vs. 3.5 months (HR 0.33, 95%CI 0.17-0.61, p = 0.0002), PFS 17.8 vs. 4.5 months (HR 0.38, 95%CI 0.21-0.67, p = 0.002), OS 24.6 vs. 6.7 months (HR 0.37, 95%CI 0.20-0.68, p = 0.002). The median time to first improvement in IVC/VC was similar in patients receiving CDK4/6i compared to paclitaxel (3.9 vs. 3.6 weeks, p = 0.773). Disease control at 4 months was not significantly different in the CDK4/6i and paclitaxel cohorts (77.8% vs. 59.4%, p = 0.168). In multivariate analysis, treatment with CDK4/6i was independently associated with a longer PFS compared to paclitaxel (HR 0.31, 95%CI 0.12-0.78, p = 0.015).

Conclusion: In this retrospective study, patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i had a significantly better survival compared to those treated with weekly paclitaxel. Further prospective studies that minimise possible selection bias are recommended.

Keywords: Advanced breast cancer; CDK4/6 inhibitor; Chemotherapy; ER positive; Paclitaxel; Visceral crisis.

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Conflict of interest statement

RB: No competing interests to declare. ACA: Spousal shares in Astra Zeneca; Honoraria for advisory boards for MSD, Gilead and Astra Zeneca; Conference fees and travel expenses from Novartis; Research funding from Astra Zeneca paid to institution. SJH: Honoraria for speaking engagements for Pfizer, Novartis and Lilly; Honoraria for advisory boards for Lilly; Joint working agreement with Lilly and Novartis.

Figures

Fig. 1
Fig. 1
CONSORT diagram for retrospective selection of study patients
Fig. 2
Fig. 2
Progression-free survival (PFS) and overall survival (OS) in subgroups of patients with ER+/HER2- advanced breast cancer (ABC) and visceral crisis (VC) or impending VC (IVC) receiving first line treatment with CDK4/6i or weekly paclitaxel a CDK4/6i cohort: PFS in endocrine therapy (ET)-sensitive/naive vs. ET-resistant ABC; b CDK4/6i cohort: OS in ET-sensitive/naive vs. ET-resistant ABC; c CDK4/6i cohort: OS in patients with disease control vs. progression at 4 months after start of treatment d Paclitaxel cohort: PFS in ET-sensitive/naive vs. ET-resistant ABC; e Paclitaxel cohort: OS in ET-sensitive/naive vs. ET-resistant ABC; f Paclitaxel cohort: OS in patients with disease control vs. progression at 4 months after start of treatment
Fig. 3
Fig. 3
Outcomes of patients receiving CDK4/6i compared to weekly paclitaxel for ER+/HER2- advanced breast cancer with visceral crisis (VC) or impending VC. a Time to treatment failure (TTF); b Progression-free survival (PFS); c Overall survival (OS)
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