The effect of CDK4/6 inhibitors on the overall survival in patients with advanced HR+/HER2- BC in the entire population and in special clinical subgroups of unfavorable prognosis: A review

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Abstract

An increase in the median progression-free survival when using cyclin-dependent kinase 4/6 inhibitors in combination with aromatase inhibitors led to high expectations from the analysis of the overall survival of patients with HR+/HER2- metastatic breast cancer. Of the three drugs in the group, the final data were obtained in the MONALEESA-2 and PALOMA-2 studies, while a statistically significant difference in median overall survival was achieved only with the use of ribociclib. The review discusses possible factors that could affect the final results of the presented studies. The effect of ribociclib on the value of OS in clinically unfavorable prognostic subgroups (for example, patients with visceral metastases) and on progression-free survival depending on the expression of molecular genetic factors that worsen patient survival (such as Rb, p16, Ki-67, CDKN2A, CCND1, ESR1) was analyzed.The combination of ribociclib and aromatase inhibitors has proven to be an advantage in the treatment of patients with HR+/HER2- metastatic breast cancer in terms of increasing both progression-free survival and overall survival. Efficacy has been proven in subgroups with clinical and molecular adverse prognostic factors.

About the authors

Katerina S. Grechukhina

Loginov Moscow Clinical Scientific Center

Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477

Cand. Sci. (Med.), Loginov Moscow Clinical Scientific Center

Russian Federation, Moscow

Maxim V. Kalugin

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-8281-5646

Department Head, Loginov Moscow Clinical Scientific Center

Russian Federation, Moscow

Andrey A. Prosvirnov

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-9600-3841

Oncologist, Loginov Moscow Clinical Scientific Center

Russian Federation, Moscow

Margarita V. Sukhova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0009-0004-7119-0160

Oncologist, Loginov Moscow Clinical Scientific Center

Russian Federation, Moscow

Liudmila G. Zhukova

Loginov Moscow Clinical Scientific Center

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-4848-6938

D. Sci. (Med.), Corr. Memb. RAS, Loginov Moscow Clinical Scientific Center

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
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2. Fig. 1. Overall survival (OS) of patients in the intention-to-treat group in the ML-2 study [13].

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3. Fig. 2. OS of patients in ML cycle studies, according to the pooled analysis, in subgroups with clinically unfavorable prognostic factors: a – with visceral metastases; b – with liver metastases; c – with 3 and more metastatic lesions [25].

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4. Fig. 3. OS of patients receiving the first line therapy in ML cycle studies, according to the pooled analysis in subgroups with clinically unfavorable prognostic factors: a – with visceral metastases; b – with liver metastases; c – with 3 and more metastatic lesions [25].

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5. Fig. 4. The efficacy of ribociclib in median PFS in patients with different molecular genetic characteristics in the ML-2 study [33].

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