not just for mice--getting ready for prime time!!
 

remember the article I posted on herceptin-pertuzumab-iressa combination "curing" mice of her2+ breast cancer

This is the result of a trial of just herceptin and pertuzumab in metastatic her2+ bc patients who have already progressed on herceptin

Note the hypomagnesemia--a described complication of antibodies blocking egfr (her1)--I had not seen it described in those blocking her2, but perhaps it is because pertuzumab, unlike herceptin, is able to block her1/2 dimerization:

HER2 Dimerization Inhibitor Pertuzumab in Combination With Trastuzumab Demonstrated Efficacy in Metastatic Breast Cancer Following Trastuzumab Progression



Multicenter phase II study

Combination of pertuzumab and trastuzumab demonstrated promising clinical benefit in patients with HER2-positive metastatic breast cancer who have progressed on trastuzumab
39% clinical benefit rate in 33 evaluable patients
Accrual ongoing
Planned recruitment: 58 patients
Combination well tolerated
Adverse events predominantly grade 1 or 2
1 occurrence (2%) of modest decline in left ventricular ejection fraction (LVEF)
Planned biomarker studies ongoing

Pertuzumab
HER2 dimerization inhibitor
Monoclonal antibody
Binds to different HER2 epitope than trastuzumab
First in a new class of HER2-targeted therapies
Potent inhibitor of HER-induced signaling
Preclinical models support complementary mechanisms of action for pertuzumab and trastuzumab
Potential for increased efficacy with combination

Current phase II study evaluated efficacy and tolerability of pertuzumab and trastuzumab in women with metastatic breast cancer who have progressed on trastuzumab

Summary of Study Design
Eligibility
HER2-positive metastatic breast cancer
Centrally confirmed by immunohistochemistry 3+ staining or by fluorescence in situ hybridization amplication
Measurable disease by Response Evaluation Criteria in Solid Tumors
? 3 previous breast cancer therapies (adjuvant and metastatic) and/or previous trastuzumab therapy
Disease progression on trastuzumab as most recent metastatic therapy
Baseline LVEF ? 55%
No decline in LVEF to < 50% during previous trastuzumab therapy
Treatment
Trastuzumab
4-mg/kg loading dose followed by 2 mg/kg once weekly or
8-mg/kg loading dose followed by 6 mg/kg every 3 weeks
Pertuzumab
840-mg loading dose followed by 420 mg every 3 weeks
Treatment initiated within 9 weeks of last dose of previous trastuzumab therapy
Outcome analysis
Primary endpoints
Efficacy
Complete response (CR) and partial response (PR) rates
Stable disease (SD)
Clinical benefit (overall response rate + SD)
Safety
Monitored by internal data and safety monitoring board
Secondary endpoints
Biomarker analysis
Baseline Characteristics
Characteristic

Pertuzumab + Trastuzumab
(n = 42)

Median age, yrs (range)

54 (34-85)

ECOG PS, %



0
74

1
19

ER positive, %

45

Involved metastatic sites, %



Visceral
79

Lung
43

Liver
50

Bone
33

Lymph nodes
43

Soft tissue
29

ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor.

Main Findings
As of April 2007
42 evaluable for safety
33 evaluable for efficacy
Response to therapy
Outcome, %

Pertuzumab + Trastuzumab
(n = 33)

CR

3.0

PR

15.2

Overall response rate

18.2

SD for 6 mos

21.2

Overall clinical benefit

39.4

SD < 6 mos

30.3

Disease progression

30.3

Other Outcomes
Adverse events
Grade 3 diarrhea in 1 patient
All other adverse events grade 1 or 2
Toxicity (All Grades), %

Pertuzumab + Trastuzumab
(n = 42 )

Diarrhea

57

Skin (nonrash)

35

Mucositis

33

Pain

33

Nausea and vomiting

33

Rash

28

Fatigue

31

Single occurrence (2% incidence)
Deep vein thrombosis
Decreased LVEF
14% decrease by local assessment, 9% decrease by central assessment
Patient asymptomatic
Hypersensitivity
Hypertension
Hypomagnesemia


Reference
Baselga J, Cameron D, Miles D, et al. Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T. Program and abstracts of the 43rd American Society of Clinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Illinois. Abstract 1004.

thanks again