Abstract P4-14-27: Effect of docetaxel duration on clinical outcomes: Results from the phase III trial CLEOPATRA
Authors: Miles D , Fung A , Yoo B , Knott A , Heeson S , Portera C , Swain S 
Published: May 2016

Abstract
Introduction:
In the CLEOPATRA study, pertuzumab (P) plus trastuzumab (T) and docetaxel (D) significantly improved median progression-free survival (PFS) and overall survival (OS) compared with placebo (Pla) plus T and D in pts with HER2-positive metastatic breast cancer. Study treatment was given every 3 weeks until disease progression (PD) or unacceptable toxicity. D starting dose was 75 mg/m2 and could be escalated or reduced per protocol. A minimum of 6 cycles of D was recommended. If D was discontinued, patients could continue P+T or Pla+T. To evaluate the potential association between D duration and clinical outcomes, we conducted post hoc exploratory analyses of the CLEOPATRA study.
Methods:
As of 11 Feb 2014 data cutoff, the safety population analyzed included 804 pts (396 Pla+T+D; 408 P+T+D) who received at least one dose of any study medication. Exposure and clinical outcomes of study treatment groups are presented by dichotomized subgroup of pts who received &lt;6 cycles of D and those who received more than 6 cycles. Median PFS and OS were estimated using Kaplan-Meier methods. Cox regression analyses were used to estimate hazard ratios (HRs).
Results:
The median number of D cycles received was 8 for both arms. Forty-one % of pts received &lt;6 (14% &lt;6; 27% exactly 6) and 59% received &gt;6 cycles.
Docetaxel Duration and Clinical Outcomes D &lt;6 cycles (n=329, 41%)D &gt;6 cycles (n=475, 59%) Pla+T+D (n=159)aP+T+D (n=170)aPla+T+D (n=237)P+T+D (n=238)Treatment Exposure#D Cycle, median (range)6 (1,6)6 (1,6)10 (7,42)10 (7,52)# Study Treatment Cycle, median (range)7 (1,78)14 (1,90)19 (7,92)28 (7,96)Duration of Study Treatment in month, median (range)6 (1,54)10 (1,63)14 (5,67)19 (5,68)Clinical OutcomesPFS in month, median (range)8.2 (6.2,9.0)12.5 (10.5,20.7)14.5 (12.6,17.2)22.8 (17.7,N/A)95% CIHR=0.59 (0.44,0.79)HR=0.65 (0.50,0.84)OS in month, median (range)29.8 (22.2,39.2)48.9 (36.8,N/A)46.7 (39.4,53.0)N/A (56.4,N/A)95% CIHR=0.67 (0.45,0.90)HR=0.62 (0.47,0.81)N/A=not available aTwo pts in each group had missing D cycle
Treatment Discontinuation Summary D &lt;6 cyclesD &gt;6 cycles Pla+T+D (n=159)P+T+D (n=170)Pla+T+D (n=237)P+T+D (n=238)D discontinuation before stopping anti-HER2 agents (n,%)90 (57)118 (69)180 (76)196 (82)Reason (n,%) AE/intercurrent illness34 (38)27 (23)60 (33)72 (37)Patient reasonb3 (3)5 (4)5 (3)8 (4)Standard practice36 (40)59 (50)65 (36)41 (21)Adequate therapy12 (13)22 (19)36 (20)59 (30)Other1 (1)1 (1)9 (5)11 (6)Missing4 (4)4 (3)5 (3)5 (3)Discontinuation of all study treatment (T+D+Pla or P), n159170237238Reason (n,%) AE/intercurrent illness15 (9)22 (13)25 (11)32 (13)Death10 (6)5 (3)4 (2)2 (1)Disease progression111 (70)110 (65)182 (77)154 (65)Patient reasonb17 (11)16 (9)12 (5)14 (6)Other6 (4)16 (9)12 (5)35 (15)Missing0 (0)1 (1)2 (1)1 (1)bIncluded failure to return, refused treatment, withdrawal, protocol violation
Conclusions:
Consistent with the overall study results, addition of P to T+D showed significant improvement in clinical outcomes regardless of whether &lt;6 or &gt;6 cycles of D were received. In the poster, three subgroup (&lt;6, 6 and &gt;6 D cycles) analyses and time-dependent Cox regression analysis to capture the dynamic variations in D exposure will be presented.
Citation Format: Miles D, Fung A, Yoo B, Knott A, Heeson S, Portera C, Swain S. Effect of docetaxel duration on clinical outcomes: Results from the phase III trial CLEOPATRA. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-27.