• Harold J Burstein, Constance T Cirrincione, William T Barry, Helen K Chew, Sara M Tolaney, Diana E Lake, Cynthia Ma, Kimberly L Blackwell, Eric P Winer, and Clifford A Hudis.
• 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.
• J. Clin. Oncol. 2014 Dec 10;32(35):3959-66.

PurposeCALGB 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 MethodsEligible 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.ResultsAt 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.ConclusionAdding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic.© 2014 by American Society of Clinical Oncology.

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