Phase II study of pegylated liposomal doxorubicin (PLD) and carboplatin (Cb) can be administered with trastuzumab (H) in patients with metastatic breast cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 6118
• Main Authors: Collea, RP, Kruter, FW, Cantrell, JE, George, TK, Kruger, S, Favret, AM, Lindquist, DL, Melnyk Jr, AM, Pluenneke, RE, Shao, SH, Crockett, MW, Asmar, L, O'Shaughnessy, JA
• Format: Journal Article
• Language: English
• Published: 15-01-2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-6118

Abstract #6118
Background: PLD and Cb are active in metastatic breast cancer (MBC) but no data exist regarding the antitumor activity of the combination. Both agents are synergistic with H in preclinical studies. The primary objective of this study was to determine the objective response rates (ORR) produced by PLD+Cb ± H.
 Patients and Methods: 133 patients (pts) were registered to the study; 125 pts were treated and were stratified by HER2 status; 124 pts are currently evaluable for response. Pts had measurable disease per RECIST criteria and had received no more than 1 prior chemotherapy regimen for MBC; HER2+ pts received therapy first-line therapy for metastatic and 4% received prior adjuvant H. All pts received PLD 30 mg/m2 IV followed by Cb, AUC=5 IV on Day 1 of 28-day cycles. In addition to PLD+Cb, HER2+ pts received H on Day 1 and Day 15 (8 mg/kg IV first dose; 4 mg/kg IV subsequent doses).
 Results: 79 pts and 46 pts received at least 1 dose of study drug on PLD+Cb (Arm 1) and PLD+Cb+H (Arm 2), respectively. Median age was 56 years. Estrogen receptor (ER) or progesterone receptor (PR) + pts and ER and PR- pts in Arm 1/Arm 2 were 63%/55% and 36%/45%, respectively, 49%/43%; pts were treated with prior doxorubicin in Arm 1/Arm 2 and 51%/30%. With prior taxane in Arm 1/Arm 2, of 79 pts on Arm 1 evaluable for response, 27% had an objective response compared with 53% of the 45 pts currently evaluable on Arm 2. Median overall survival was 17 months in Arm 1 and as not been reached in Arm 2. Median PFS is 5 and 10 months for Arm 1 and 2, respectively. The most common Grade 3-4 treatment-related toxicities for Arm 1/Arm 2 were: neutropenia 23%/35%, leukopenia 13%/22%, thrombocytopenia 20%/17%, fatigue 6%/13%, and anemia 11%/9%.
 Conclusion: PLD+Cb in combination have moderate activity in MBC; also, the addition of H to PLD+Cb in HER2+ pts enhanced its activity. Preliminary toxicity results suggest that PLD can be safely combined with H with minimal cardiac toxicity. Final data analyses from this fully enrolled study will be reported at SABCS 2008.
 This research was supported, in part, by a research grant from Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6118.