344P - Pharmacokinetics (PK) of pertuzumab (P) with trastuzumab (T) and docetaxel (D) in HER2-positive first-line metastatic breast cancer (mBC): results f...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Breast Cancer
Biological therapy
Presenter Javier Cortes Castan
Authors J. Cortes Castan1, S. Swain2, I. Kudaba3, M. Hauschild4, T. Patel5, E. Grincuka6, N. Masuda7, V. McNally8, J. Visich9, J. Baselga10
  • 1Oncologia, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 2Washinton Cancer Institute, 20010 - Washington/US
  • 3Oncology Center, Riga East University Hospital, Riga/LV
  • 4Spital Rheinfelden & Laufenburg, Gesundheitszentrum Fricktal, Rheinfelden/CH
  • 5The Mark H. Zangmeister Center, Mid Ohio Oncology/Hematology, Inc., Columbus/US
  • 6Department Of Oncology, Daugavpils Regional Hospital, Daugavpils/LV
  • 7Surgery And Breast Oncology, NHO Osaka National Hospital, Osaka/JP
  • 8Products Limited, Roche, Welwyn/UK
  • 9Genentech, Genentech, South San Francisco/US
  • 10Hematology/oncology, MGH Cancer Center, Massachusetts General Hospital, MA 02114 - Boston/US



P is a humanized mAb that inhibits heterodimerization of HER2. P and T bind distinct HER2 epitopes, and due to their complementary mechanisms of action they provide a more comprehensive blockade of HER2 signaling. Based on preclinical efficacy models, a steady-state trough P concentration (Ctrough) of 20 ug/ml was selected as target in pts. CLEOPATRA is a Phase III study comparing P + T + D vs placebo (Pla) + T + D in HER2-positive 1L MBC (Baselga NEJM 2012). The objectives of the substudy reported here are to characterize the P PK in the presence of T and D, and to explore potential drug − drug interactions.


P/Pla (840 mg loading, 420 mg maintenance) was administered on Day 1 of each cycle; T (8 mg/kg loading, 6 mg/kg maintenance) was administered on Day 2 of Cycle 1 and on Day 1 of each cycle onward following P; D (75 mg/m2, escalation to 100 mg/m2 if tolerated) was administered on Day 2 of Cycle 1 following T and on Day 1 of each cycle onward following T. All drugs were given q3w iv. Blood samples for P were collected before and after infusion at Cycles 1, 3, 6, 9, 12, 15, 18, and at treatment discontinuation. Samples for T were collected before and after infusion at Cycles 1 and 3. Samples for D were collected at Cycle 1 at 8 serial time points during and following the infusion over a 24 h period to allow calculation of Cmax, CL, Vss, t1/2, AUC0–t, and AUC0-inf.


37 pts (17 Pla arm, 20 P arm) were available for PK evaluation. Serum P Ctrough exceeded the target of 20 ug/ml in >90% of pts and there was no impact of T and D on P PK, compared with historical data. Mean serum T Cmax and Cmin at Cycles 1 and 3 were similar in both arms. Ratios of geometric LS means of P + T + D/Pla + T + D x100 for serum T were: Cycle 1 Cmax 90.3; Cycle 3 Cmin 95.9; Cycle 3 Cmax 81.0. D PK parameters were similar in both arms. Ratios of geometric LS means of P + T + D/Pla + T + D x100 for plasma D were: AUC0–t 104.9, AUC0-inf 101.4, Cmax 92.5.


P PK parameters were consistent with previous studies, and co-administration of T and D appears not to influence P PK in HER2-positive MBC. There was no evidence of drug − drug interactions between P and T, or between P and D, which have different clearance pathways.


J. Cortes: I am an advisory board member for Roche, Celgene and Novartis. I have received research funding from Roche, Celgene, Cephalon and Ferrer.

S. Swain: Advisory Board for Genentech/Roche for EMILIA study and Avastin - uncompensated. Research funding: Genentech/Roche.

T. Patel: I have an advisory board membership for Genentech/Roche to disclose and are a speaker for Genentech/Roche. I have received research funding from Genentech/Roche.

N. Masuda: I have honoraria to disclose received from Chugai Pharmaceutical Co., Ltd.

V. McNally: I am a Roche employee and hold Roche shares.

J. Visich: I am an employee of Genentech.

J. Baselga: Dr Baselga reports the following relationships with relation to the topic of this abstract: Roche, Sanofi Aventis, Consulting/Scientific Advisory Board. Roche, Sanofi Aventis, Honoraria for speaking engagements.

All other authors have declared no conflicts of interest.