Risk of selected gastrointestinal toxicities in breast cancer patients treated with regimens containing lapatinib; a pooled analysis of randomized controlled studies

Abstract

We performed a pooled analysis of randomized controlled studies evaluating selected gastrointestinal adverse events associated with lapatinib use in breast cancer patients. Eligible studies included randomized Phase II and III trials of patients with breast cancer on lapatinib; describing events of diarrhea, nausea, vomiting and stomatitis. Our search strategy yielded 390 potentially relevant citations on lapatinib from Pubmed/Medline and other databases. After exclusion of ineligible studies, a total of 19 clinical trials were considered eligible for the analysis. The relative risk (RR) of all-grade diarrhea, nausea, vomiting and stomatitis were 3.09 (95% CI: 2.14–4.43; p < 0.00001), 1.24 (95% CI: 1.07- 1.43; p < 0.005), 1.35 (95% CI: 1.22–1.49; p = 0.0001), 1.96 (95% CI: 1.07–2.67; p = 0.02); respectively. Exploratory subgroup analysis showed no effect of disease stage on the RR of the relevant adverse events. While, The RR of high-grade diarrhea, nausea, vomiting and stomatitis were 6.63 (95% CI: 2.94–14.96; p < 0.00001), 1.37 (95% CI: 0.91–2.06; p = 0.13), 1.80 (95% CI: 1.21–2.68; p = 0.004), 2.44 (95% CI: 1.41–4.22 p < 0.001); respectively. Our pooled analysis has demonstrated that regimens containing lapatinib are associated with a significantly increased risk of high-grade diarrhea, vomiting and stomatitis in patients with breast cancer. Clinicians should be aware of these risks and perform regular clinical monitoring.

Keywords::

• breast cancer
• diarrhea
• lapatinib
• pooled analysis
• vomiting

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

Background

• Lapatinib is an orally active multityrosine kinase inhibitor that dually targets multiple EGFR and HER2 pathways.

• Currently, the US FDA has approved lapatinib for patients with advanced HER2-positive breast cancer. However, continued use of trastuzumab beyond progression may offer an alternative with less GI toxicities

• EGFR tyrosine kinase inhibitors, including lapatinib, have been linked to a unique spectrum of adverse events most notably including gastrointestinal adverse events.

Methodology

• In this review, we performed a pooled analysis of selected gastrointestinal toxicities associated with lapatinib use in breast cancer treatment.

• Eligible studies included randomized Phase II and III trials of patients with breast cancer on lapatinib describing events of diarrhea, nausea, vomiting and stomatitis.

Results

• After proper selection of the studies, a total of 19 randomized clinical trials were considered eligible for the analysis.

• Patients treated with lapatinib had a significantly increased risk of all-grade diarrhea, nausea, vomiting and stomatitis.

• Our exploratory subgroup analysis showed no effect of treatment regimen or disease stage on the RR of the relevant adverse events.

• Clinicians should be aware of these risks and perform regular gastrointestinal monitoring.