Median follow-up was 12.9 months (range, 0-34 months) in the T-DM1 arm and 12.4 months (range, 0-35 months) in the capecitabine plus lapatinib arm.
Results showed that by independent review, PFS was significantly longer in T-DM1 patients, a median of 9.6 vs 6.4 months for those in the capecitabine plus lapatinib arm (HR=0.650 [95% CI: 0.55–0.77]; P<0.0001, Dr. Blackwell said; by investigator review, HR=0.658 (95% CI: 0.56–0.77); P<0.0001.
Subgroup analysis for PFS by prespecified stratification factors showed all groups did better in the T-DM1 arm—including world region, and number of prior chemotherapy regimens—except those with absence of visceral disease; median PFS was 10.2 months in the capecitabine plus lapatinib arm vs 8.5 months in the T-DM1 arm (HR=0.96 [95% CI: 0.71–1.30]. By baseline characteristic, ER and PR status, line of therapy, and age <65 years favored T-DM1 (median PFS was 6.0 months for capecitabine plus lapatinib vs 9.8 months for T-DM1). However, for patients ≥65 years of age, median PFS was 8.1 months with capecitabine plus lapatinib vs 7.0 months for T-DM1 (HR=1.06 [95% CI: 0.68–1.66]).
Interim analysis of OS favored T-DM1; median OS was 23.3 months for capecitabine plus lapatinib vs not reached for T-DM1; stratified HR=0.621 (95% CI 0.48–0.81); P=0.0005 but did not cross the efficacy stopping boundary (P=0.0003 or HR=0.617). One-year OS was 84.7% in the T-DM1 arm vs 77% in the capecitabine plus lapatinib arm; 2-year OS was 65.4% and 47.5%, respectively.
In patients with measureable disease, ORR was 43.6% in the T-DM1 arm and 30.8% in the capecitabine plus lapatinib arm, a difference of 12.7% (95% CI: 6.0–19.4); P=0.0002. Median duration of response was 6.5 months (95% CI: 5.5–7.2) in the capecitabine plus lapatinib arm vs 12.6 months (95% CI: 8.4–20.8) in the T-DM1 arm.
The Functional Assessment of Cancer Therapy (FACT)-Breast Trial Outcome index7 was used to evaluate physical well-being, functional well-being, and breast cancer-specific symptoms among trial participants, Dr. Blackwell reported. Symptom progression was defined as ≥5-point decrease from baseline. In the capecitabine plus lapatinib arm, patient-reported median time to symptom progression was 4.6 months vs 7.1 months in the T-DM1 arm (HR=0.80 [95% CI: 0.67–0.95]; P=0.0121).
T-DM1 was well tolerated with no unexpected safety signals. A total of 57% patients in the capecitabine plus lapatinib arm had grade 3/4 AEs vs 40.8% in T-DM1. The most common grade ≥3 hematologic adverse events (AEs) that occurred more frequently in the T-DM1 arm were thrombocytopenia (12.8% vs 0.2%) and anemia (2.7% vs 1.6%; no grade 4 in either arm). Grade ≥3 hematologic AEs occurring more frequently in the capecitabine plus lapatinib arm were neutropenia (4.3% vs 2.0%) and febrile neutropenia (1.0% vs 0%).
Nonhematologic events occurring more frequently in the T-DM1 arm were increased AST (4.3% vs 0.8%) and ALT (2.9% vs 1.4%); in the capecitabine plus lapatinib arm these were diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0), vomiting (4.5% vs 0.8%), hypokalemia (4.1% vs 2.2%), fatigue (3.5% vs 2.4%), nausea (2.5% vs 0.8%), and mucosal inflammation (2.3% vs 0.2%). Dose reductions occurred in 16.3% of patients receiving T-DM1, 53.4% for capecitabine and 27.3% for lapatinib.