Lapatinib in HER2-positive digestive tract cancers: Moving on to phase III development?

Targeting with trastuzumab improves survival

  • Date: 09 Oct 2016

Combination platin-based perioperative chemotherapy plus surgery is the standard of care for patients with operable oesophagogastric adenocarcinoma.1 For those patients with advanced gastric or gastro-oesophageal junction (OGJ) cancer who are positive for HER2, targeting it with trastuzumab improves survival.2 Yesterday, Professor Eric Van Cutsem presented data from a poster by Dr Elizabeth Smyth at The Royal Marsden NHS Foundation Trust, London, UK (Abstract LBA26) that sought to determine whether adding the dual HER1/HER2 tyrosine kinase inhibitor, lapatinib, to epirubicin, cisplatin plus capecitabine (ECX) was feasible in HER2-positive patients with operable, gastric or OGJ cancer, or lower oesophageal adenocarcinoma.

In this phase II, open-label study, 46 patients were randomised to three pre- and three post-operative ECX cycles, or investigational treatment with ECX plus lapatinib 1,250 mg/day during each chemotherapy cycle and for 6 further maintenance cycles. In the ECX plus lapatinib arm, 4/20 patients required lapatinib dose reduction and 4/19 patients experienced diarrhoea of grade 3 or higher (versus no patients in the ECX arm). Although this regimen was feasible, whether lapatinib will proceed to phase III development in this setting is currently undecided.

While new potential cancer treatments are a cause for optimism, some caution should be exercised. Toxicity associated with lapatinib and ECX can be high, leading some clinicians to call into question its suitability as a combination therapy in new drug development; similar toxicity data were reported with adjuvant lapatinib in patients with HER2-positive early breast cancer (ALTTO trial).3

1. Glatz T, et al. Eur J Surg Oncol 2015;41:1300–7
2. Bang YJ, et al. Lancet 2010;376:687–97
3. Piccart-Gebhart M, et al. J Clin Oncol 2016;34:1034–42

This article appeared in the Sunday edition of the Daily Reporter