Endocrine therapy with or without inhibition of epidermal growth factor receptor
and human epidermal growth factor receptor 2: a randomized, double-blind,
placebo-controlled phase III trial of fulvestrant with or without lapatinib for
postmenopausal women with hormone receptor-positive advanced breast cancer-CALGB
40302 (Alliance).
Author(s): Burstein HJ(1), Cirrincione CT(2), Barry WT(2), Chew HK(2), Tolaney SM(2), Lake
DE(2), Ma C(2), Blackwell KL(2), Winer EP(2), Hudis CA(2).
Affiliation(s): Author information:
(1)Harold J. Burstein, William T. Barry, Sara M. Tolaney, and Eric P. Winer,
Dana-Farber Cancer Institute, Boston, MA; Constance T. Cirrincione, Duke
University Alliance Statistics and Data Center; Kimberly L. Blackwell, Duke
University Medical Center, Durham, NC; Helen K. Chew, University of California,
Davis, Davis, CA; Diana E. Lake and Clifford A. Hudis, Memorial Sloan Kettering
Cancer Center, New York, NY; and Cynthia Ma, Washington University School of
Medicine, St Louis, MO. hburstein@partners.org. (2)Harold J. Burstein, William T.
Barry, Sara M. Tolaney, and Eric P. Winer, Dana-Farber Cancer Institute, Boston,
MA; Constance T. Cirrincione, Duke University Alliance Statistics and Data
Center; Kimberly L. Blackwell, Duke University Medical Center, Durham, NC; Helen
K. Chew, University of California, Davis, Davis, CA; Diana E. Lake and Clifford
A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; and Cynthia Ma,
Washington University School of Medicine, St Louis, MO.
Publication date & source: 2014, J Clin Oncol. , 32(35):3959-66
PURPOSE: CALGB 40302 sought to determine whether lapatinib would improve
progression-free survival (PFS) among women with hormone receptor-positive
metastatic breast cancer treated with fulvestrant.
PATIENTS AND METHODS: Eligible women had estrogen receptor-positive and/or
progesterone receptor-positive tumors, regardless of human epidermal growth
factor receptor 2 (HER2) status, and prior aromatase inhibitor treatment.
Patients received fulvestrant 500 mg intramuscularly on day 1, followed by 250 mg
on days 15 and 28 and every 4 weeks thereafter, and either lapatinib 1,500 mg or
placebo daily. The study planned to accrue 324 patients and was powered for a 50%
improvement in PFS with lapatinib from 5 to 7.5 months.
RESULTS: At the third planned interim analysis, the futility boundary was
crossed, and the data and safety monitoring board recommend study closure, having
accrued 295 patients. At the final analysis, there was no difference in PFS
(hazard ratio [HR] of placebo to lapatinib, 1.04; 95% CI, 0.82 to 1.33; P = .37);
median PFS was 4.7 months for fulvestrant plus lapatinib versus 3.8 months for
fulvestrant plus placebo. There was no difference in overall survival (OS) (HR,
0.91; 95% CI, 0.68 to 1.21; P = .25). For HER2-normal tumors, median PFS did not
differ by treatment arm (4.1 v 3.8 months). For HER2-positive tumors, lapatinib
was associated with longer median PFS (5.9 v 3.3 months), but the differential
treatment effect by HER2 status was not significant (P = .53). The most frequent
toxicities were diarrhea, fatigue, and rash associated with lapatinib.
CONCLUSION: Adding lapatinib to fulvestrant does not improve PFS or OS in
advanced ER-positive breast cancer and is more toxic.
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