Pegylated liposomal doxorubicin for PIK3CA “wild”, HR⁺, HER^2-, chemoresistant advanced breast cancer

Abstract

Author(s): Movchan Oleksii Volodimirovich*, Smolanka Ivan Ivanovich, Lyashenko Andriy Oleksandrovich, Loboda Anton Dmitrovich, Dosenko Irina Viktorivna and Ivankova Oksana Mykolaivna

Introduction: In 2023, nearly 19 million individuals were newly diagnosed with cancer, with breast cancer accounting for 12.7% of all cases. Many efforts were made to reduce the negative effects of doxorubicin while increasing its efficacy. Pegylated Liposomal Doxorubicin (PLD) is a medicine that claims to fulfill these two objectives due of its distinct pharmacokinetic characteristics. Differential activity in patients with PIK3CA-altered vs. PIK3CA-wild-type, estrogen receptor-positive metastatic breast cancer that has progressed during or after antiestrogen treatments. By conducting a comparison analysis with typical anthracycline regimens, this study, using data from earlier studies, tries to understand the possible benefits of PLD.

Purpose: To evaluate the efficacy and safety of Pegylated Liposomal Doxorubicin (PLD) in patients with PIK3CA-wild, HR+, HER-, Chemo resistant Advanced Breast Cancer (CABC), treated with anthracycline and taxanes.

Material and methods: First group (wild PIK3CA) – 30 patients were treated with pegylated liposomal doxorubicin 50 mg/m2 diluted in 5% dextrose 250 ml intravenous infusion for 1 hour on day every 28 days – four cycles; second group (mutant PIK3CA) – 30 patients were treated with pegylated liposomal doxorubicin 50 mg/m2 diluted in 5% dextrose 250 ml intravenous infusion for 1 hour on day every 28 days – four cycles.

Results: The PIK3CA-mutant arm had a median OS of 32.54 months (HR=0.76; 95% CI, 0.68-0.86; one-sided P=0.08) compared to 31.34 months in PIK3CAwild arm (HR=0.78; 95% CI, 0.62-0.98; one-sided P=0.06).

Conclusions: By evaluating all patients treated with single-agent PLD at our Research Institute, we demonstrated that the outcomes of PLD in patients with CABC HR+HER2-PIK3CAwild did not match previously published data from prospective observational studies. The observed results in PIK3CA-wild were not significantly inferior to the total population. PLD remains a viable therapy option in these more sensitive patient populations. PLD-based neoadjuvant chemotherapy may give considerable benefits in terms of OS for CABC patients. The findings highlight the possibility of this treatment regimen as a more effective and probably less toxic alternative to traditional chemotherapy, with long-term advantages that might change existing treatment procedures.

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