Pegylated liposomal doxorubicin (PLD) plus docetaxel significantly improves time to progression (TTP) compared with docetaxel (D) monotherapy in patients with advanced breast cancer (ABC) treated with adjuvant anthracycline: results from a randomized phase 3 study.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #80 Background: Earlier studies have showed that PLD (DOXIL®/CAELYX®) has comparable efficacy but is significantly less cardiotoxic than conventional doxorubicin for the treatment of ABC. We sought to determine whether women with ABC who had relapsed at least 1 year after prior adjuvant anthracycline would derive clinical benefit from the addition of PLD to D without an increase in cardiac toxicity. Methods: 751 pts were randomly assigned to receive either D 75 mg/m2 (N=373) or PLD 30 mg/m2 followed by D 60 mg/m2 (N=378) on Day 1 every 21 days. Treatment was to continue until disease progression or the occurrence of unacceptable toxicity. The primary endpoint was TTP and secondary endpoints were overall survival (OS), objective response rate (ORR), cardiac and overall safety. The analysis for TTP was planned after approximately 485 events and for final OS after 485 deaths. Results: This prespecified TTP analysis was performed after 555 TTP events. Median TTP was increased from 7.0 months for D, to 9.8 months for the PLD+D (HR=0.65; 95% CI 1.41, 2.35; P =0.000001), and the ORR was also significantly improved for the PLD+D (26% vs. 35% P =0.0085). OS was similar between the two arms at the time of this interim analysis with 374 (50%) total deaths (HR=1.06; 95% CI 0.86;1.30). Both groups received a median of 6 cycles. Grade 3/4 neutropenia was reported in 66% and 65% of pts on PLD+D arm and D arm, respectively; the incidence of pts with febrile neutropenia was 7% and 6%, respectively, and the overall incidence of pts with grade 3-4 drug-related adverse events was 74% and 66%, respectively. There was no increase in cardiac toxicity, as determined by reported cardiac adverse events or LVEF measurements in the PLD+D arm compared with the D arm. Congestive heart failure was reported in 3 (1%) pts in the PLD+D arm and 4 (1%) pts in the D arm. Grade 3/4 hand-foot syndrome (HFS) and stomatitis were reported for 24% and 11% of PLD+D pts and infrequently in the D group (1% and 1%, respectively). Discussion: Treatment with PLD+D combination results in statistically significant improvement of TTP and ORR compared with D among pts with ABC without an increased risk of cardiac toxicity. Additional follow-up is needed to determine the impact of the combination on OS. HFS and stomatitis occurred more often in pts treated with PLD+D therapy. The addition of PLD to a D-based regimen is a safe and effective option for pts with ABC previously treated with adjuvant anthracycline regimens. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 80.