Second-Line Lapatinib ‘Insufficient’ in HER2-Amplified Metastatic Gastro-Oesophageal Cancer

Phase II trial of lapatinib versus lapatinib plus capecitabine in advanced gastro-oesophageal cancer suspended early owing to futility

medwireNews: Lapatinib , either alone or in combination with capecitabine , fails to show sufficient activity in pretreated patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic gastro-oesophageal adenocarcinoma, report German researchers.

The phase II trial was terminated prematurely, not as a result of either the prespecified interim analysis or an accrual of serious adverse episodes or death, say Florian Lordick, from University Medicine Leipzig, and co-authors, but because of a high likelihood of the study endpoints not being reached.

“In view of the currently available evidence from several studies, including ours, one must conclude that [lapatinib] is probably not an effective agent for treating [gastro-oesophageal cancer]”, the team writes in the European Journal of Cancer.

In this multicentre trial, individuals with metastatic gastro-oesophageal adenocarcinoma harbouring HER2 amplification were randomly assigned to receive either lapatinib 1500 mg per day for a 21-day treatment cycle or lapatinib 1250 mg daily plus capecitabine on days 1 to 14 of the cycle. All participants had previously progressed with at least one platinum-based first-line therapeutic regimen.

A partial or complete response was noted in none of the 19 patients given lapatinib alone and in two of the 18 treated with lapatinib plus capecitabine, giving an objective response rate of 0% and 11%, respectively.

Median time to progression was 42 days in the lapatinib monotherapy group and 83 days in the lapatinib plus capecitabine group, while median overall survival was 142 days and not reached, respectively.

“The responses observed in our study can potentially be attributed to [capecitabine] treatment alone”, say the researchers.

Although the incidence of grade 3 or higher adverse events was comparable between the treatment arms (10 in each), Florian Lordick et al note that patients in the combination arm experienced “more toxicity”.

“The excess in adverse events in the combination therapy group appeared specific to the toxicity profile of capecitabine, with patients more likely to suffer from mild diarrhoea, stomatitis and hand-foot syndrome.”

Three patients in the monotherapy and six in the dual therapy group discontinued treatment as a result of disease progression, which the team says is testament not only to the “very poor” prognosis of this disease, but also to an “ineffective” therapy.


Lorenzen S, Knorrenschild JR, Haag G-M, et al. Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: A randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Eur J Cancer 2015; Advance online publication 16 February. doi:10.1016/j.ejca.2015.01.059

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