Analysis of dermatologic events in patients with cancer treated with lapatinib
M E Lacouture1, S M Laabs, M Koehler
1Department of Dermatology, Northwestern University, 676 North St. Claire Street, Suite 1600, Chicago, IL 60611-2941, USA. m-lacouture@northwestern.edu
Purpose:
Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized.
Patients And Methods:
Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n=928) or in combination with paclitaxel or capecitabine (n=491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions.
Results:
Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in
Conclusions:
Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.
Insights
Dermatologic events (DEs) in cancer patients treated with lapatinib are common but typically mild and appear early. These side effects, including rash, rarely require dose changes, differing from other EGFR TKI events.
Area of Science:
- Oncology
- Pharmacology
- Dermatology
Background:
- Lapatinib is a small-molecule dual tyrosine kinase inhibitor targeting EGFR and HER2.
- Dermatologic events (DEs) are known side effects of tyrosine kinase inhibitors (TKIs).
Purpose of the Study:
- To characterize dermatologic events in cancer patients receiving lapatinib.
- To compare lapatinib-associated DEs with those of other EGFR TKIs.
Main Methods:
- Analysis of nine clinical trials involving metastatic cancer patients treated with lapatinib (monotherapy or combination).
- Characterization of DEs based on type, onset, severity, duration, and interventions.
- Comparison with a control group not treated with lapatinib.
Main Results:
- DEs occurred in 58% (monotherapy) and 74% (combination) of lapatinib-treated patients versus 53% in controls.
- The most frequent DE was rash (43%); most events were grade 1/2 and developed within 14 days.
- Only 3% of DEs led to dose reduction, 7% to interruption, and 1% to discontinuation.
Conclusions:
- Most lapatinib-associated DEs are early-onset, mild-to-moderate, and infrequently necessitate dose modification.
- Lapatinib-induced DEs appear clinically distinct in frequency and severity compared to other EGFR TKIs.
