title: 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).
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Adding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic.
authors.affiliation: 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.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.affiliation: 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.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.affiliation: 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.
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.affiliation: 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.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Chew
authors.affiliation: 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.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tolaney
authors.affiliation: 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.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Lake
authors.affiliation: 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.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Blackwell
authors.affiliation: 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.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: 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.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D000077267:Fulvestrant; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D000077267:Fulvestrant; D006728:Hormones; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human