Efficacy and safety of first-line (1L) pertuzumab (P), trastuzumab (T), and docetaxel (D) in HER2-positive MBC (CLEOPATRA) in patients previously exposed to trastuzumab

• Published in: Journal of clinical oncology Vol. 31; no. 15_suppl; p. 600
• Main Authors: Ciruelos Gil, Eva Maria, Brufsky, Adam, Im, Young-Hyuck, Kim, Sung-Bae, Clark, Emma, Knott, Adam, Ross, Graham, Miles, David
• Format: Journal Article
• Language: English
• Published: 20-05-2013
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2013.31.15_suppl.600

Abstract only 600 Background: CLEOPATRA is a global phase III trial of P + T + D vs placebo + T + D in HER2-positive 1L MBC. Results showed a significant improvement in PFS (Baselga NEJM 2012) and OS (Swain SABCS 2012) favoring P + T + D. CLEOPATRA started recruitment in 2008 soon after the approval of T in the adjuvant setting in 2006 and mandated a disease-free interval (DFI) of ≥12 mos from the end of adjuvant therapy to MBC diagnosis. Due to this, a low proportion of pts with prior T exposure was included. Here we present the efficacy and safety of 1L P + T + D in the subset of pts in CLEOPATRA with prior T exposure. Methods: Pts received P + T + D or placebo + T + D, had a DFI ≥12 mos, baseline left ventricular ejection fraction (LVEF) ≥50% and no LVEF decline to <50% during/after prior T therapy. Exploratory analyses of PFS and OS in pts with (neo)adjuvant therapy with or without T were conducted. Results: Of the study population, 47% had received (neo)adjuvant therapy and 11% had received (neo)adjuvant T; 82% of the prior T group came from Europe or North America. A univariate Cox regression analysis did not identify prior T therapy as a statistically significant risk factor for developing left ventricular systolic dysfunction (LVSD). However, due to the low number of LVSD events overall, this analysis has limited sensitivity. Conclusions: Data from CLEOPATRA show that pts with HER2-positive 1L MBC who have received prior T (DFI ≥12 mos) derive the same magnitude of benefit from the combination of P + T + D when compared with the whole study population or those who are T-naïve. This is in agreement with prior evidence of the activity of P + T in pts pretreated with T (Baselga JCO 2010). Efficacy and safety of P-T-based therapy is being explored in the PERUSE and PHEREXA trials, in a pt population with wider exposure to prior T and a shorter DFI, which may better represent current clinical practice. Clinical trial information: NCT00567190. [Table: see text]