Lapatinib in combination with paclitaxel conferred no overall survival benefit over paclitaxel alone for patients with advanced HER2-positive gastric cancer.
However, the combined treatment did show some benefit for those whose cancers were highly expressed, Dr. Taroh Satoh and his colleagues wrote online May 27 in the Journal of Clinical Oncology (J. Clin. Oncol. 2014 May 27 [doi: 10.1200/JCO.2013.53.6136]).
The Asian study also found that Chinese patients responded better to the combination treatment than did Japanese patients, said Dr. Satoh of Osaka University, Japan, and his coauthors.
The year-long TyTAN (Tykerb with Taxol in Asian HER2-Positive Gastric Cancer) study randomized 261 patients (mean age, 60 years) to two treatment arms: oral lapatinib (Tykerb) 1,500 mg once per day plus paclitaxel (Taxol) 80 mg/m2 infusions on days 1, 8, and 15 of a 4-week cycle; or paclitaxel 80 mg/m2 alone.
The study included patients from Japan, mainland China, South Korea, and Taiwan. All cancers were HER2-positive by fluorescence in situ hybridization.
There was no difference in median overall survival between the combination and monotherapy groups (11 vs. 9 months, respectively; P = .104). The median progression-free survival time and time to progression were similar in the combination and monotherapy groups (5.5 vs. 4.4 months, respectively).
Response duration was numerically longer with the combination treatment (7.4 vs. 5 months), but that difference was not statistically significant. However, significantly more patients taking the combination did respond to treatment (27% vs. 9%; odds ratio, 3.85).
Subgroup analyses revealed some significant differences in treatment effect. Patients who had not undergone a gastrectomy did better when they took the combination therapy, with an overall 37% decrease in the risk of disease progression or death compared with paclitaxel alone. Patients with highly expressed HER2 cancers did better on the combination as well, with a 41% reduced risk of death, a longer period of progression-free survival (5.6 vs. 4.2 months), and a 46% reduction in the risk or death. Patients with poorly or moderately expressed HER2 didn’t experience any significantly improved benefits with the combination over paclitaxel alone.
The subgroup analysis also found that Chinese patients responded better to the combination treatment than to monotherapy, with significantly better overall survival (9.7 vs. 7.6 months) and progression-free survival (7.2 vs. 4.7 months). Japanese patients did not experience significant benefits in either of these outcomes.
The most common adverse events were diarrhea, alopecia, and neutropenia. Combination therapy was associated with more adverse events leading to discontinuation than paclitaxel alone (16% vs. 9%). The most frequent of these were diarrhea (3 patients) and decreased appetite (3) in the combination group, and peripheral sensory neuropathy (3) in the monotherapy group.
There was a high incidence of neutropenia (65% in the combination group; 50% in the monotherapy group), with nine patients in the combination group and two in the monotherapy group developing febrile neutropenia.
There were more nonfatal serious adverse events in the lapatinib plus paclitaxel group than in the paclitaxel-alone group (26% vs. 15%). These included febrile neutropenia, reduced appetite, neutropenia, pneumonia, abdominal pain, nausea, device-related infection, diarrhea, and vomiting. Diarrhea, alopecia, neutropenia, and leucopenia were more common in Japanese than Chinese patients.
Nine patients experienced a total of 10 fatal adverse events. Six of these were in the combination group, with four considered to be treatment related (diarrhea, acute myocardial infarction, acute left ventricular failure, and cardiac arrest).
Three patients in the monotherapy group experienced a total of four fatal adverse events (subileus, gastrointestinal perforation, and gastrointestinal hemorrhage), but they were not considered treatment related. Three of the fatal events were cardiac and considered to be paclitaxel related. All occurred in Chinese patients.
The study was sponsored by GlaxoSmithKline. Dr. Satoh has received honoraria from GlaxoSmithKline and Bristol-Myers Squibb. Many of the coauthors also disclosed relationships with GlaxoSmithKline and other companies.