Abstract P6-15-06: SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety
Authors: Gil-Gil M , Bellet M , Morales S , Barnadas A , Manso L , Morilla Ruiz I , Azaro A , Ciruelos Gil E , Garcia Martínez E , Marínez N , Melé M , Soler T , Villagrasa P , Pernas S 
Published: February 2018

Abstract
Background:
Anthracycline and taxane-based chemotherapy is the standard treatment for high-risk breast cancer. However, conventional anthracyclines are not commonly used in elderly patients or those patients prone to cardiotoxicity and there is a potential risk leaving them undertreated. Pegylated liposomal doxorubicin (PLD) has comparable efficacy, but significantly less cardiotoxicity than conventional anthracyclines. We conducted a phase II trial to assess the efficacy and safety of a neoadjuvant chemotherapy (NC) based on PLD and paclitaxel (PTX) in this group of patients. The pathological complete response, breast conservative surgery (BCS) and safety data at a 35-month follow-up were published (Gil-Gil et al. Breast Cancer Res Treat 2015). Here we present the final analysis of 5-year overall survival (OS) and 5-year disease-free survival (DFS) and cardiac safety after 60 months of follow-up.
Methods:
Fifty patients with stage II (48%) and III (52%) breast cancer (seven cases were T4d) and with at least one risk factor for developing cardiotoxicity were included. NC schedule: PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 every 4 weeks for four cycles, followed by 80 mg/m2 weekly PTX for 12. Median age was 73 years old (84% were older than 65 years). Forty-eight (96%) of tumors were triple negative (TN). Secondary objectives included 5-year DFS, 5year OS and cardiac safety measured by a decrease in left ventricular ejection fraction (LVEF), electrocardiogram (ECG) anda cardiac questionnaire performed every 3 months during the first year, every 6 months year 2-3 and every 12 months year 4-5 of follow-up.
Results: Forty-eight patients (96%) completed the 4 cycles of PLD plus CPM, while only 26 patients (52%) could complete the 12 weeks of PTX. Forty-six patients (92%) underwent surgery. After surgery: 27 patients received radiotherapy, 2 letrozole and 1 trastuzumab. The 5-year OS was 56% (95% CI 41.2-68.4) and the 5-year DFS was 54.4% [95% CI: 38.3-67.9].No significant decrease in LVEF was seen (mean baseline LVEF was 66.6 (52-86) and mean LVEF after 60 months was 66 (54.5-73). Four patients (8%) developed cardiotoxicity (in 2 cases G3). There were 5 non-cancer deaths (10%): 3 during treatment (all in patients &gt; 80 years: a sudden death one month after surgery, a haemorrhagic stroke 30 days after completing chemotherapy and a non-neutropenic pneumonia); and 2 during follow-up (1 Amyotrophic Lateral Sclerosis and 1 intestinal ischemia).
Conclusions:
PLD followed by PTX as NC was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. The 5 year DFS and 5 year OS in elderly patients with bulky TN tumors were similar tothe reported in the literature. This regimen could be an option for the neoadjuvant treatment of cardiotoxicity-prone patients or elderly patients who present high-risk breast cancer.
Citation Format: Gil-Gil M, Bellet M, Morales S, Barnadas A, Manso L, Morilla Ruiz I, Azaro A, Ciruelos Gil E, Garcia Martínez E, Marínez N, Melé M, Soler T, Villagrasa P, Pernas S. SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-06.