Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.
BACKGROUND
This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.


METHODS
A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale).


RESULTS
In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm.


CONCLUSIONS
Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life.
Medical Office Hematology, Aschaffenburg, Germany.
Manfred
M
Welslau
Veronique
V
Diéras
Joo-Hyuk
JH
Sohn
Sara A
SA
Hurvitz
Deepa
D
Lalla
Liang
L
Fang
Betsy
B
Althaus
Ellie
E
Guardino
David
D
Miles
D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006304:Health Status; D006801:Humans; D000077341:Lapatinib; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008875:Middle Aged; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D057566:Self Report; D011795:Surveys and Questionnaires; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D016903:Drug Monitoring
D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
HER2-positive; T-DM1; ado-trastuzumab emtansine; antibody-drug conjugate; breast cancer; quality of life