Abstract P6-11-07: A Phase IV Trial of Caelyx as First Line Chemotherapy (CT) in Women 65 Years or Older with Locally Advanced or Metastatic Breast Cancer: In Search for Treatment Predictive Factors

Background: Anthracyclines belong to the most effective therapies for patients (pts) with breast cancer. Toxicity limits its use in elderly women where, beside nausea, vomiting, hair loss and the risk for infections, cardiotoxicity is of special concern. Caelyx is pegylated liposomal doxorubicin, a formulation diminishing the risk for the mentioned side effects but with a risk for skin toxicity known as Palmar-Plantar Erythrodysesthesia (PPE). As Caelyx is generally well-tolerated, we investigated its value as first-line CT in women 65 years or older. We also collected a variety of tumor and patient markers in search of predictors of outcome and toxicity. Methods: Women age ≥65 years, with inoperable locally advanced or metastatic breast cancer with performance status (PS) WHO 0-2, measurable disease according to RECIST or WHO criteria for bone metastasis or non-measurable disease, Left Ventricular Ejection Fraction (LVEF) ≥50% and normal organ function, received 40 mg/m2 Caelyx every 28 days. Pts underwent tumor evaluation including LVEF every 3 months. Primary endpoint was time to treatment failure (TTF) defined as progression of disease or unacceptable toxicity. Secondary endpoints were s afety, response rate (RR), time to progression (TTP), overall survival (OS), and analysis of treatment predictive factors in tumor tissue. Also the ABCB1 (=Multi Drug Resistance gene 1) single nucleotide polymorphism (SNP) was investigated. Results: 25 women were included in the study. Median age was 72 years (range 65-81). The median TTF was 5.5 months and the mean number of cycles received was 7.4 (range 1-21). 22 pts were followed by RECIST or a combination of RECIST and WHO. Of these one achieved a partial response (PR) and 11 stable disease (SD). The median TTP was 5.7 months and the median OS was 20.6 months. The majority of adverse events (AE9s) were mild to moderate and transient, the main toxicities being nausea 60% (grade I/II/III 24/32/4), fatigue 56% (40/12/4) and PPE 52% (24/20/8). Clinically significant changes in LVEF were noted in three pts. Severe AE9s occurred in 8 pts. And the dose was reduced due to toxicity in 4 pts. Analysis of the ABCB1 SNPs revealed that pts with homozygous mutation for SNP G2677T had significantly shorter time to treatment failure and time to progression as compared to the rest of the pts. Those with the 3435T/T genotype were more susceptible to moderate to severe PPE (5 out of 8 with SNP 3435T/T as compared to 2 out of 16 non-3435T/T pts). Conclusion: Breast cancer in elderly patients in need of CT can be challenging because of the risk of toxicity, reduced quality of life and also the lack of tumor response. To be able to select the right patient for a certain therapy would be essential. We treated 25 elderly women with advanced breast cancer with Caelyx with acceptable toxicity and efficacy. We also found that SNPs in ABCB1 correlated with both TTP and the risk of PPE, thereby indicating that the ABCB1 genotype could be a predictive factor for treatment with Caelyx in elderly women. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-07.