P3-14-27: Pegylated Liposomal Doxorubicin (PLD) as Primary Treatment in Estrogen Receptor (ER) and HER2 Poor Breast Cancer and Risk of Developing Cardiotoxicity or Elderly Patients (pt). Results from the Phase II CAPRICE Study.
Authors: MJ Gil, C Bellet, A Llombart, B Ojeda, L Manso, C Mesia, S Morales, H García-Martinez, N Martínez, M Melé, A Fernández-Ortega, J Baselga
Journal: Cancer Research (2011)

Abstract Background: Combinations of doxorubicin (DX) and taxanes are considered the standard treatment in high risk breast cancer, but classical DX is not commonly used in elderly pt or in those with risk of developing cardiotoxicity. PLD (Caelyx/Doxil® is associated with less cardiotoxicity. We present a multicentric phase II trial conducted by SOLTI group. A combination of PLD and cyclophosphamide (CP) followed by paclitaxel (PTX) was tested as primary chemotherapy (CT) in pts with stage II-IIIB breast cancer with poor estrogen receptor positivity (&amp;lt; 50% positive nuclei) and at least one risk factor of developing cardiotoxicity. Our aim was to demonstrate a pathologic complete response (pCR) rate similar of prior DX studies without cardiac toxicity. Method: PLD 35 mg/m2 + CP 600 mg/m2 were administered every 4 weeks (w) for 4 cycles followed by PTX 80 mg/m2 every w for 12 w. Left ventricular ejection fraction (LVEF), ECG and cardiac questionnaire were performed at baseline and 8, 16, 28, 40 w thereafter. The primary end point was pCR. Secondary endpoints included: cardiac safety, radiological response rate (RRR), breast conserving surgery (BCS) rate, toxicity and overall survival at 5 years. Results: 50 pt were included. Median age: 73 (35-84), 42 pt &amp;gt; 65 years old; 32 pt (64%) suffer from hypertension and 7 had prior cardiac disease. Histological grade III: 36 pts (72%); stage II/III: 24/26 pt respectively; only 13 pts (26%) were candidate for BCS at diagnosis. 46 pt (92%) underwent surgery: BCS 27 (58.6%) and mastectomy 19 (41.3%); 4 pt did not proceed to surgery due to serious adverse events. In an intent-to-treat analysis pCR rate in breast was 32% (95% CI 19.5−46.7%), 22% (95% CI 10.5−33.4%) in breast and nodes. Among triple negative pt (N=48) pCR was 33.3%. Two of seven T4d pt (28.7%) achieved pCR. No significant decrease in LVEF was seen: Mean baseline LVEF was 66.6% (52-86), 66.7 (51-88) after 16w, 62.2 (48-75) after 28w and 64.7 (50-74) after 40 w. Other toxicities: edema 10%, alopecia 10%, neutropenia 10%, stomatitis 8%, neurotoxicity 8%, skin reactions 6%, Hand-Food Syndrome 6%. Grade III-V toxicities were reported in 10 patients (20%): cardiovascular 3, diarrhea 2, rash 2, lung 2 and neutropenia 1. Three non-cancer deaths occurred: 1 sudden death in a 82 year's old pt one month after surgery, 1 due to hemorrhagic stroke &amp;gt; 30 days after completing CT pt with prior cerebrovascular disease, and another 84 year's old due to non-neutropenic pneumonia during CT. Conclusions: This schedule of primary chemotherapy achieves a pCR rate similar to the standard treatment and is feasible in a group of patients for whom DX was contraindicated. This strategy enables to double the BCS rate. Toxicity was acceptable in a very fragile cohort of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-27.