Study Reports Improved Survival With Lapatinib and CapeOx in Asian and Younger Patients With HER2-Positive Advanced Gastroesophageal Adenocarcinoma
In a phase III trial (TRIO-013/LOGiC) reported in the Journal of Clinical Oncology, Hecht et al found that the addition of lapatinib (Tykerb) to capecitabine-oxaliplatin (CapeOx) in patients with previously untreated HER2-amplified advanced gastroesophageal adenocarcinoma did not improve overall survival among all patients. However, lapatinib was associated with improved overall survival in Asian patients and in those aged < 60 years.
Study Details
In this double-blind trial, 545 patients from 186 sites in 22 countries were randomly assigned between June 2008 and January 2012 to receive capecitabine at 1,700 mg/m2 in two daily doses on days 1 to 14 and oxaliplatin at 130 mg/m2 on day 1 (for up to eight cycles) every 21 days plus lapatinib at 1,250 mg (n = 272) or placebo (n = 273). The primary endpoint was overall survival in patients with centrally confirmed HER2 amplification in the primary efficacy population, consisting of 487 patients randomly assigned to receive lapatinib (n = 249) or placebo (n = 238).
For the lapatinib and placebo groups in the primary efficacy population, the median age was 61 and 59 years (overall, 236 patients aged < 60 years); 76% and 74% were male; HER2 immunohistochemistry status was 0 in 5% and 6%, 1+ in 14% and 8%, 2+ in 23% and 21%, and 3+ in 57% and 65%; Eastern Cooperative Oncology Group performance status was 0 or 1 in 92% and 90%; 7% and 8% had prior neo/adjuvant treatment; the region was North America for 3% and 4%, Asia for 40% and 39%); the primary site was esophageal in 5% and 3%, gastric in 86% and 88%, and gastroesophageal junction in 9% and 8%; the extent of disease was metastatic in 95% in both; and the number of metastatic sites was two in 37% and 36% and at least three in 31% and 37%.
Overall Survival
In the primary efficacy population, median overall survival was 12.2 months (95% confidence interval [CI] = 10.6–14.2 months) in the lapatinib group vs 10.5 months (95% CI = 9.0–11.3 months) in the placebo group (hazard ratio [HR] = 0.91, P = .3492); median progression-free survival was 6.0 months (95% CI = 5.6–7.0 months) vs 5.4 months (95% CI = 4.4–5.7 months; HR = 0.82, P = .0381); and the response rate was 53% vs 39% (P = .0031).
In preplanned exploratory analyses, median overall survival among 193 Asian patients was 16.5 months (95% CI = 13.3–20.2 months) with lapatinib vs 10.9 months (95% CI = 9.0–14.9 months) with placebo (HR = 0.68, P = .0261), compared with 10.0 months (95% CI = 8.0–12.0 months) vs 9.1 months (95% CI = 8.3–10.9 months; HR = 1.04, P = .7781) among 277 patients in the “rest of the world” subgroup.
Among the 236 patients aged < 60 years, median overall survival was 12.9 months (95% CI = 11.1–16.0 months) with lapatinib vs 9.0 months (95% CI = 7.8–11.3 months) with placebo (HR = 0.69, P = .0141), compared with 11.3 months (95% CI = 8.4–13.8 months) vs 10.9 months (95% CI = 9.6–14.1 months; HR = 1.08, P = .5923) among 251 patients aged ≥ 60 years. No correlation was observed between HER2 immunohistochemistry status and survival.
Adverse Events
The most common adverse events of any grade among 270 lapatinib and 267 placebo patients in the safety population were diarrhea (58% vs 29%), nausea (49% vs 43%), and vomiting (44% vs 36%). The most common grade ≥ 3 adverse events were diarrhea (13% vs 3%), nausea (6% vs 2%), and vomiting (6% vs 4%). Serious adverse events occurred in 27% vs 19%, and adverse events led to discontinuation of treatment in 21% vs 19%. Four fatal adverse events were attributed to the study treatment in the lapatinib group, and one was attributed to the study treatment in the placebo group.
The investigators concluded: “Addition of lapatinib to CapeOx did not increase [overall survival] in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation.”
The study was supported by GlaxoSmithKline and Novartis Pharma AG.
J. Randolph Hecht, MD, of David Geffen School of Medicine at UCLA, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
