Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study

Miguel Gil‐Gil; Meritxell Bellet; Milana Bergamino; Serafín Morales; Agustí Barnadas; Luís Manso; Cristina Saura; Adela Fernández-Ortega; Elena García-Martínez; Noelia Martínez-Jáñez; Mireia Melé; Patricia Villagrasa; P. Céliz; Xavier Pérez Martín; Eva Ciruelos; Sònia Pernas

doi:10.3389/fonc.2021.645026

July 9, 2021Frontiers in OncologyOpen Access

Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study

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Why the study?

The study evaluated neoadjuvant pegylated liposomal doxorubicin in elderly patients or those with cardiovascular risk factors in whom conventional doxorubicin was contraindicated.

Does neoadjuvant pegylated liposomal doxorubicin maintain cardiac safety and provide effective survival outcomes in elderly or cardiotoxicity-prone patients with breast cancer?

Structured PICO

Does neoadjuvant pegylated liposomal doxorubicin maintain cardiac safety and provide effective survival outcomes in elderly or cardiotoxicity-prone patients with breast cancer?

P

Population

n=50 breast cancer patients (88% triple negative) who are elderly or have cardiovascular risk factors making conventional doxorubicin contraindicated. Median age 73.

I

Intervention

Pegylated liposomal doxorubicin every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy

O

Outcome

Pathological complete response (pCR), 5-year cardiac safety (LVEF monitoring), disease-free survival (DFS), breast cancer specific survival (BCSS), and overall survival (OS)safety

Neoadjuvant pegylated liposomal doxorubicin is a cardiac-safe alternative for elderly or high-cardiovascular-risk patients with breast cancer, showing no significant long-term LVEF decline.

Implication

May support PLD in high cardiac-risk patients; leaves open phase 3 confirmation of long-term outcomes.

Abstract

BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). METHODS: ) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed. RESULTS: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%). CONCLUSION: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov reference NCT00563953.