Maintenance Lapatinib Not Supported In HER1/2-Positive Metastatic Bladder Cancer

Lapatinib no better than placebo for improving post-chemotherapy survival in a biomarker-enriched population of metastatic urothelial cancer patients

medwireNews: maintenance treatment with lapatinib does not improve outcomes in patients with metastatic urothelial cancer positive for human epidermal growth factor receptor (HER) 1 or HER2 expression, shows a placebo-controlled trial.

The primary endpoint of progression-free survival (PFS) did not vary significantly between the lapatinib and placebo groups, at a median of 4.5 and 5.1 months, respectively.

Median overall survival (OS) was likewise comparable, at 12.6 months for lapatinib-treated patients and 12.0 months for those given placebo.

The UK research team did not find any significant PFS or OS benefit associated with the HER1 and HER2 tyrosine kinase inhibitor in participants strongly positive for HER1/HER2 (3+ on immunohistochemistry) or in those positive for only HER1 or HER2, “which reinforces the lack of benefit.”

The rates of toxicity-related discontinuation and of grade 3 or 4 adverse events were comparable between the lapatinib and placebo groups, at 6.0% versus 5.0% and 8.6% versus 8.1%, respectively.

The double-blind, phase III trial included 232 patients with HER1- or HER2-positive metastatic urothelial cancer who had not progressed during four to eight cycles of chemotherapy. An equal number of participants (n=116) were randomly assigned to receive oral lapatinib 1500 mg/day or placebo between 4 and 10 weeks after completing chemotherapy.

Thomas Powles, from Queen Mary University of London, and co-authors say that their strategy could have been unsuccessful for a several reasons. For instance, “although the targeting of HER proteins in isolation in breast cancer has been successful, they may not be a target associated with clinical benefit in [urothelial bladder cancer]”, they write in the Journal of Clinical Oncology.

Moreover, despite being active in other HER-positive malignancies, lapatinib “may not have activity in [urothelial bladder cancer], and other methods of targeting the HER family may be preferable”, suggest the researchers.

They also concede that the choice of biomarker may be partly responsible for the findings, and “[g]ene expression or amplification methodologies may be preferable” in the urothelial cancer setting.

Reference

Powles T, Huddart RA, Elliott T, et al. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2–positive metastatic bladder cancer. J Clin Oncol; Advance online publication 31 October 2016. doi:10.1200/JCO.2015.66.3468

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