Skin events (SE) among 1,126 patients (Pts) treated with lapatinib (L), an oral dual ErbB1/2 tyrosine kinase inhibitor (TKI)

Abstract

9102 Background: Lapatinib (L) is active as a single agent and in combination with capecitabine in pts with ErbB2+ve breast cancer. Safety profile from > 5,000 pts demonstrates infrequent Grade (G)3/4 (10%) adverse events, with drug discontinuation (disc) required in (<2%) events. SEs were commonly reported and were likely due to ErbB1 inhibition in the epidermis, as hypothesized with the other ErbB1 TKIs. However, the SE with L appear to differ clinically from other TKIs. Methods: SE in 1,126 pts reported in 8 L trials ( EGF20001 , EGF20002 , EGF20003 , EGF20004 , EGF20008 , EGF20009 , EGF20014 , + EGF100151) were pre-defined as dermatitis, drug eruption, dry skin, pruritus/urticaria, skin disorder, skin infection, nail, and hair disorder. SE were characterized based on CTC grading, and examined as to their relationship to L dose, length of L exposure, tumor type, concurrent treatment, time to onset from L initiation, and time to resolution with L dose- reduction or disc. Furthermore clinical management, skin biopsies, photos, and outcome were examined. Results: Pts were treated with L monotherapy 1,000–1,500mg daily (N=928), or in combination with capecitabine (C) (N=198). Non-L containing arms of studies EGF100151 (N=191; C alone) and EGF20001 (N=197; tamoxifen alone) served as controls. Among all L treated pts, 54% experienced SE mostly as G1/2, and 69% L+C pts experienced G1–3 SE with 50% G2. Majority of SE were deemed not specific to L and were rarely severe (no G4). Only 1% required drug disc. Most frequently reported SEs were dermatitis/drug eruption (38% all grade; 3% G3) (8% all grade, 1% G3). The frequency of SE with L at 1,500 mg QD was 57%, 1250 mg QD was 41%, and 500 BID was 63%. Most SE developed early (45% day 1–14) and persisted a median of 29 days. The majority of L pts (82%) did not require intervention (ie, dose reduction, hold, or withdraw). Conclusions: This large collection of L treated pts demonstrates that SE related to L therapy are low grade, infrequently require intervention or dose reduction, and rarely cause drug disc. Further attempts to identify pts at high risk for skin toxicity, its management, and the pathophysiology of L related SE are ongoing. No significant financial relationships to disclose.

Review: Side Effects of Approved Molecular Targeted Therapies in Solid Cancers

“…Most recently, skin events among 1,126 patients treated with lapatinib, across eight trials, were analyzed, with dermatitis (all grades) occurring in 38% of patients, and 3% being grade 3 [71]. Regarding the potential cardiotoxicity of lapatinib, Perez et al [72] analyzed cardiac function in 3,558 patients treated with lapatinib in 43 phase I-III clinical trials.…”

Targeted treatment of advanced and metastatic breast cancer with lapatinib

“…This appears to be a class effect of drugs which inhibit EGFR, including gefitinib and erlotinib, and may be mediated by EGFR inhibition in the epidermis ( Gordon et al 2005 ; Cersosimo 2006 ; Geyer et al 2006 ; Lacouture 2006 ). A recent review analyzed adverse skin events in 1419 patients from 8 lapatinib trials ( Sweetman et al 2007 ). These trials included lapatinib monotherapy (n = 928), and lapatinib in combination with capecitabine or paclitaxel (n = 491).…”

“…However, most events were low grade (53% grade 1 or 2; 6% grade 3; none grade 4) and treatment discontinuation was required in 1% of cases. Most lapatinib related events occurred early (within 14 days), and were distributed mainly on the trunk, and less frequently on the face ( Sweetman et al 2007 ).…”