Abstract P4-12-10: Safety of pertuzumab (P) with trastuzumab (T) and docetaxel (D) in patients (pts) from Asia with HER2-positive metastatic breast cancer (MBC): Results from the phase III trial CLEOPATRA
Authors: Swain SM , Im Y-H , Im S-A , Miles D , Knott A , Clark E , Ross G , Baselga J 
Published: August 2014

Abstract
Background: CLEOPATRA is a phase III study of placebo (Pla)+T+D and P+T+D in HER2-positive first-line MBC. The combination of both HER2-targeted antibodies, P+T, with D resulted in significantly improved progression-free survival (PFS) and overall survival (OS). The incidence of febrile neutropenia (FN) was higher with P+T+D versus Pla+T+D. We present analyses of adverse events (AEs) and treatment patterns for pts from Asia.
Methods: Pts were from Asia, Europe, North and South America. Study drugs were given intravenously, q3w: P/Pla, 840 mg initial dose, then 420 mg; T, 8 mg/kg initial dose, then 6 mg/kg; D, 75 mg/m2 with escalation to 100 mg/m2 if tolerated. Treatment was given until disease progression or unacceptable toxicity; 6 cycles of D were recommended, &gt;6 cycles were at investigator's discretion. Dose modifications of P or T were not permitted. Two D dose reductions by 25% to 75 mg/m2 and 55 mg/m2 were allowed in order to manage toxicities; re-escalation was not permitted.
Results: The safety population comprised 253 pts from Asia (Pla+T+D: 128; P+T+D: 125) and 551 pts from other regions (Pla+T+D: 269; P+T+D: 282). The incidences of neutropenia, FN, diarrhea, mucosal inflammation, grade ≥3 AEs overall, and serious AEs were higher with P+T+D versus Pla+T+D. In the P arm, the largest increase in AEs in pts from Asia versus other regions was observed for FN and mucosal inflammation. D dose was more frequently reduced in pts from Asia; however, the incidence of AEs leading to discontinuation of all study treatment was balanced between pts from Asia and other regions. PFS and OS were improved with P+T+D in pts from all regions. In the whole study population, the hazard ratios (HR) for PFS and OS were 0.63 (95% CI 0.52-0.76) and 0.66 (0.52-0.84), respectively. In pts from Asia, the HR was 0.68 (0.48-0.95) for PFS and 0.64 (0.41-1.00) for OS. These efficacy analyses were unstratified.
Pts with event, n (%)Other regionsAsia Pla+T+DP+T+DPla+T+DP+T+D n = 269n = 282n = 128n = 125Neutropenia123 (46)141 (50)74 (58)74 (59)FN15 (6)24 (9)15 (12)32 (26)Diarrhea118 (44)179 (63)66 (52)93 (74)Mucosal inflammation56 (21)67 (24)23 (18)46 (37)Grade ≥3 AEs194 (72)199 (71)95 (74)103 (82)Serious AEs69 (26)82 (29)35 (27)58 (46)AEs leading to discontinuation of all study treatment15 (6)21 (7)6 (5)4 (3)D dose escalation to 100 mg/m256 (21)47 (17)5 (4)1 (1)D dose reduction to &lt;75 mg/m232 (12)42 (15)57 (45)62 (50)Use of granulocyte colony-stimulating factor (G-CSF) to treat FN8 (3)11 (4)12 (9)30 (24)Subsequent G-CSF prophylaxis in pts with FN6 (2)3 (1)1 (1)11 (9)Study treatment cycles, median15181520D cycles, median8799
Conclusions: AEs did not result in reduction of the median number of cycles administered in pts from Asia compared with other regions. However, given that 47% of pts from Asia had D dose reductions &lt;75 mg/m2 with comparable survival benefits to pts from other regions, a reduction in the D starting dose should be considered in these pts. Based on the efficacy and safety profile of P+T+D, this regimen is the preferred treatment option for pts with HER2-positive first-line MBC from all geographic regions.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-10.