Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in the CLEOPATRA study

• Published in: Journal of clinical oncology Vol. 30; no. 15_suppl; p. 533
• Main Authors: Ewer, Michael, Baselga, José, Clark, Emma, Benyunes, Mark, Ross, Graham, Swain, Sandra M.
• Format: Journal Article
• Language: English
• Published: 20-05-2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.15_suppl.533

Abstract only 533^
Background: Addition of trastuzumab (T) to chemotherapy has transformed outcomes in pts with HER2-positive breast cancer. In pts who had received anthracyclines (A), T has been associated with cardiac dysfunction. Monitoring cardiac tolerability of anticancer drugs is important, including that of a new regimen combining T with a second anti-HER2 antibody that inhibits HER2 dimerization, pertuzumab (P). In CLEOPATRA, efficacy and safety of P+T+docetaxel (D) were studied in HER2-positive 1
st
-line MBC (Baselga 2012). Methods: CLEOPATRA, a randomized, double-blind, placebo-controlled, ph III trial, enrolled 808 pts; 804 were included in the safety population. A baseline (BL) LVEF ≥50%, no history of congestive heart failure, and no LVEF decline to <50% during/after prior T were required. Treatment was administered q3w until disease progression or unmanageable toxicity (P/placebo [Pla]: 840 mg, followed by 420 mg; T: 8 mg/kg, followed by 6 mg/kg; D [≥6 cycles recommended]: 75 mg/m
2
, escalating to 100 mg/m
2
if tolerated). LVEF was assessed by ECHO or MUGA at BL, every 9 wks during treatment, at discontinuation, and up to 3 yrs thereafter. Adverse events (AE) were monitored continuously and graded according to NCI-CTCAE v3.0. Results: The incidence of any cardiac disorder (grade ≥1) as assessed by the investigators was similar with Pla+T+D (16.4%) and P+T+D (14.5%). LVSD (grade ≥1) was the most frequent cardiac AE and more common with Pla+T+D. At the time of data cutoff for this analysis, 8/11 symptomatic LVSD events had resolved; none fatal. All pts who developed symptomatic LVSD had ≥1 potential cardiac risk factor (prior A, prior T, radiation, smoking, diabetes, hypertension, other). Compared to the overall pt population, only prior A and radiation were higher in pts who developed symptomatic LVSD. Conclusions: CLEOPATRA provides evidence that P+T+D does not increase overall cardiac disorders, specifically symptomatic LVSD, compared to Pla+T+D. [Table: see text]