Adverse events with pertuzumab and trastuzumab: Evolution during treatment with and without docetaxel in CLEOPATRA.

Breast Cancer - HER2/ER
Session Type and Session Title: 
General Poster Session, Breast Cancer - HER2/ER
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 597^)
José Baselga, Javier Cortes, Seock-Ah Im, Xavier B. Pivot, Emma Clark, Adam Knott, Graham Ross, Sandra M. Swain; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Department of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain; Division of Hematology/Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; CHU Jean Minjoz, Besançon, France; Roche Products Limited, Welwyn Garden City, United Kingdom; Washington Cancer Institute, MedStar Washington Hospital Center, Washington, WA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: In CLEOPATRA, the HER2-dimerization inhibitor pertuzumab (P) was combined with trastuzumab (T) and docetaxel (D) in HER2-positive 1st-line MBC. P+T+D significantly improved efficacy compared with placebo (Pla)+T+D while having little effect on safety. Pts were recommended to receive ≥6 cycles of D but could discontinue D prior to Cycle 6 due to poor tolerability or progressive disease (PD) or continue D beyond Cycle 6 at investigators’ discretion. Once D was discontinued, pts received Pla+T or P+T until PD. To understand the full safety profile of the regimen, adverse events (AEs) occurring before and after D discontinuation were analyzed. Methods: Treatment was given q3w (Pla/P: 840 mg loading, then 420 mg; T: 8 mg/kg loading, then 6 mg/kg; D: 75 mg/m2, escalating to 100 mg/m2 if tolerated; de-escalation by 25% allowed). AEs were graded according to NCI-CTCAE v3.0, monitored continuously during the treatment period, and their relationship to study drugs was assessed by investigators. Results: From 808 pts enrolled, 804 were analyzed in the safety population (pts who received ≥1 dose of study treatment). AEs that led to discontinuation of all study treatment were experienced by 5.3% (Pla+T+D) and 6.1% (P+T+D) of pts, whereas discontinuation of D alone due to AEs occurred in 23.2% (Pla+T+D) and 23.6% (P+T+D) of pts. Conclusions: Treatment in both arms was well tolerated. After discontinuation of D, there was a clear reduction in grade ≥3 AEs; however, the incidence of grade ≥3 diarrhea remained slightly elevated with P+T+D. The AE profile of P+T is consistent with that seen in previous Phase II studies (Gianni Lancet Oncol 2012; Baselga JCO 2010). These data suggest that the combination of P+T may also be well tolerated in other breast cancer settings, such as in adjuvant therapy, which is currently under phase III study (APHINITY; NCT01358877).
Grade ≥3 AEs, incidence >5%.
AE, n (%) Incidence during
all study treatment
Incidence after
D discontinuation
Pla+T+D (n=397) P+T+D (n=407) Pla+T (n=255) P+T (n=298)
Neutropenia 182 (45.8) 199 (48.9) 4 (1.6) 0 (0.0)
Febrile neutropenia 30 (7.6) 56 (13.8) 0 (0.0) 0 (0.0)
Leukopenia 58 (14.6) 50 (12.3) 1 (0.4) 0 (0.0)
Diarrhea 20 (5.0) 32 (7.9) 0 (0.0) 3 (1.0)