JCO Early Release, published online ahead of print Feb 1 2010
Journal of Clinical Oncology, 10.1200/JCO.2008.21.4437
Received December 8, 2008
Accepted August 21, 2009
Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer
Kimberly L. Blackwell,* Harold J. Burstein, Anna Maria Storniolo, Hope Rugo, George Sledge, Maria Koehler, Catherine Ellis, Michelle Casey, Svetislava Vukelja, Joachim Bischoff, Jose Baselga, and Joyce O'Shaughnessy
From the Duke University Medical Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Medicine Development Center Oncology, GlaxoSmithKline, Collegeville, PA; Texas Oncology, PA, US Oncology, Tyler; Baylor Sammons Cancer Center, Texas Oncology, PA, US Oncology, Dallas, TX; Otto von Guericke Univeristäte, Madgeburg, Germany; and Vall d'Hebron University Hospital, Barcelona, Spain.
* To whom correspondence should be addressed. E-mail: black034{at}mc.duke.edu
Purpose: Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC).
Patients and Methods: Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab. The primary end point was progression-free survival (PFS). Secondary efficacy end points included overall response rate (ORR), clinical benefit rate (CBR; complete response, partial response, and stable disease for  24 weeks), and overall survival (OS).
Results: In the intent-to-treat population (N = 296) who received a median of three prior trastuzumab-containing regimens, the combination of lapatinib with trastuzumab was superior to lapatinib alone for PFS (hazard ratio [HR] = 0.73; 95% CI, 0.57 to 0.93; P = .008) and CBR (24.7% in the combination arm v 12.4% in the monotherapy arm; P = .01). A trend for improved OS in the combination arm was observed (HR = 0.75; 95% CI, 0.53 to 1.07; P = .106). There was no difference in ORR (10.3% in the combination arm v 6.9% in the monotherapy arm; P = .46). The most frequent adverse events were diarrhea, rash, nausea, and fatigue; diarrhea was higher in the combination arm (P = .03). The incidence of symptomatic and asymptomatic cardiac events was low (combination therapy = 2% and 3.4%; monotherapy = 0.7% and 1.4%, respectively).
Conclusion: Despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
Related Articles
- Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Sharmila Makhija, Lukas C. Amler, Dana Glenn, Frederick R. Ueland, Michael A. Gold, Don S. Dizon, Virginia Paton, Chin-Yu Lin, Thomas Januario, Kimmie Ng, Andreas Strauss, Stephen Kelsey, Mark X. Sliwkowski, and Ursula Matulonis
JCO 2010 28: 1215-1223
[Abstract]
[Full Text]
- Open-Label, Phase II, Multicenter, Randomized Study of the Efficacy and Safety of Two Dose Levels of Pertuzumab, a Human Epidermal Growth Factor Receptor 2 Dimerization Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer
Luca Gianni, Anna Lladó, Giulia Bianchi, Javier Cortes, Pirkko-Liisa Kellokumpu-Lehtinen, David A. Cameron, David Miles, Stefania Salvagni, Andrew Wardley, Jean-Charles Goeminne, Veronica Hersberger, and José Baselga
JCO 2010 28: 1131-1137
[Abstract]
[Full Text]
- Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy
José Baselga, Karen A. Gelmon, Shailendra Verma, Andrew Wardley, PierFranco Conte, David Miles, Giulia Bianchi, Javier Cortes, Virginia A. McNally, Graham A. Ross, Pierre Fumoleau, and Luca Gianni
JCO 2010 28: 1138-1144
[Abstract]
[Full Text]
- Optimizing the Delivery of Targeted Research: An Opportunity for Comparative Effectiveness Research
Kathleen I. Pritchard
JCO 2010 28: 1089-1091
[Full Text]
- Whither HER2-Related Therapeutics?
Pradip De and Brian Leyland-Jones
JCO 2010 28: 1091-1096
[Full Text]
This article has been cited by other articles:
|
|
|
|
 
N. L. Spector and K. L. Blackwell
Reply to F. Bellati et al
J. Clin. Oncol.,
July 20, 2010;
28(21):
e371 - e371.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dang, N. Lin, B. Moy, S. Come, S. Sugarman, P. Morris, A. Abbruzzi, C. Chen, R. Steingart, S. Patil, et al.
Dose-Dense Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/neu-Overexpressed/Amplified Breast Cancer Is Not Feasible Because of Excessive Diarrhea
J. Clin. Oncol.,
June 20, 2010;
28(18):
2982 - 2988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vogel, A. Chan, B. Gril, S.-B. Kim, J. Kurebayashi, L. Liu, Y.-S. Lu, and H. Moon
Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib
Jpn. J. Clin. Oncol.,
June 11, 2010;
(2010)
hyq084v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. O'Brien, B. C. Browne, L. Chow, Y. Wang, C. Ginther, J. Arboleda, M. J. Duffy, J. Crown, N. O'Donovan, and D. J. Slamon
Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib
Mol. Cancer Ther.,
June 1, 2010;
9(6):
1489 - 1502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. I. Pritchard
Optimizing the Delivery of Targeted Research: An Opportunity for Comparative Effectiveness Research
J. Clin. Oncol.,
March 1, 2010;
28(7):
1089 - 1091.
[Full Text]
[PDF]
|
|
|
|
