Abstract P5-18-01: Pertuzumab (P) in combination with trastuzumab (T) and docetaxel (D) in elderly patients with HER2-positive metastatic breast cancer in the CLEOPATRA study
Authors: Miles D , Baselga J , Amadori D , Sunpaweravong P , Semiglazov V , Knott A , Clark E , Ross G , Swain SM 
Published: August 2014

Abstract
Background: The incidence of cancer increases with age as does the risk of treatment-related adverse events (AEs) due to underlying comorbidities. A better understanding of cancer therapy-related AEs in elderly pts may help identify the optimal therapy by balancing treatment benefit and risk. CLEOPATRA, a double-blind Phase III trial, compared placebo (Pla)+T+D with P+T+D in pts with HER2-positive 1L MBC (Baselga 2012). Here we report safety and efficacy by age group.
Methods: P/Pla: 840 mg initial dose, 420 mg q3w iv; T: 8 mg/kg initial dose, 6 mg/kg q3w iv; D: 75 mg/m2 q3w iv, escalating to 100 mg/m2 if tolerated. P/Pla+T were given until progressive disease (PD) or unacceptable toxicity. At least 6 cycles of D were recommended; &lt;6 cycles were allowed for PD or unacceptable toxicity, &gt;6 cycles were allowed at investigators' discretion. At baseline, pts were required to have ECOG PS of 0 or 1, LVEF ≥50% and no decline to &lt;50% during or following prior T therapy. The cumulative exposure to prior doxorubicin must not have exceeded 360 mg/m2 or its equivalent. The primary endpoint was independently assessed PFS; secondary endpoints included overall survival, objective response, safety.
Results: In the safety population, 678 pts (332 Pla arm, 346 P arm) were &lt;65 yrs and 126 pts (65 Pla arm, 61 P arm) were ≥65 yrs. In pts &lt;65 yrs, the median number of D cycles was 8 (1–41) in the Pla arm (median D dose intensity: 24.8 mg/m2/week) and 8 (1–35) in the P arm (24.5 mg/m2/week). The median number of D cycles was lower in pts ≥65 yrs, with 6.5 (1–26) in the Pla arm (24.8 mg/m2/week) and 6 (1–16) in the P arm (24.8 mg/m2/week). In elderly pts, the incidence of diarrhea, fatigue, and dysgeusia appeared to be higher in both arms, whereas neutropenia and febrile neutropenia were reported less frequently. Grade ≥3 diarrhea was reported in 4.8% (Pla arm) and 6.6% (P arm) of pts &lt;65 yrs and in 6.2% (Pla arm) and 14.8% (P arm) of pts ≥65 yrs. In a univariate Cox regression analysis, age had no statistically significant association with the development of asymptomatic or symptomatic left ventricular systolic dysfunction (LVSD); however, due to the low number of LVSD events overall this analysis has limited sensitivity to detect differences in time to event by age group. An exploratory post hoc analysis of independently assessed PFS in the ITT population showed a median PFS of 12.5 months in the Pla arm and 17.2 months in the P arm (HR = 0.65, 95% CI 0.53–0.80) in pts &lt;65 yrs. In pts ≥65 yrs, the median PFS was 10.4 months in the Pla arm and 21.6 months in the P arm (HR = 0.52, 95% CI 0.31–0.86).

Conclusions: Overall, the AE profile reported in CLEOPATRA suggests that, in pts with good performance status, the use of P should not be limited by age. Therapy with P+T+D resulted in improved efficacy in pts aged &lt; and ≥65 yrs.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-01.