1. Maintenance Lapatinib After Chemotherapy in HER1/2-Positive Metastatic Bladder Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. Lapatinib in HER1/2-Positive Bladder Cancer: Background
Lapatinib: dual inhibitor of HER1 and HER2
High HER1/2 expression may have negative prognostic significance in bladder cancer
Prior phase II study reported greater survival benefit with lapatinib in pts overexpressing HER1 or HER2[1]
Current analysis is a randomized, double-blind phase II/III trial that evaluated maintenance lapatinib vs placebo after first-line chemotherapy in HER1/2+ metastatic bladder cancer[2]
1. Wülfing et al. Cancer. 2009;115: Powles T, et al. ASCO Abstract 4505.

3. Maintenance Lapatinib in HER1/2-Positive Bladder Cancer: Study Design
Stratified by chemotherapy response, PS (0 vs ≥ 1)
Lapatinib 1500 mg QD
(n = 116)
HER1/2 screening
Metastatic or advanced HER1/2-positive bladder cancer
(N = 446)
First-line
chemotherapy
If HER1/2+
and
clinical
benefit
(n = 232)
Placebo
(n = 116)
OS, overall survival; PFS, progression-free survival; PS, performance status; QD, once daily.
Primary endpoint: PFS
Secondary endpoints: OS, safety
Exploratory endpoints: subset analyses
Powles T, et al. ASCO Abstract 4505.

4. Maintenance Lapatinib in HER1/2-Positive Bladder Cancer: Baseline Characteristics
Lapatinib (n = 116)
Placebo (n = 116)
Male, %
75.9
72.4
Median age, yrs
70.7
71.1
Performance status 0, %
45.7
44.8
Response to chemo, %
CR/PR SD
69.0
31.0
67.2
32.8
HER status, %
HER1+
HER2+
HER1/2+
18.1
36.2
42.2
39.7
Previous cisplatin, %
64.0
65.2
CR, complete response; PR, partial response; SD, stable disease.
Powles T, et al. ASCO Abstract 4505.

5. Maintenance Lapatinib in HER1/2-Positive Bladder Cancer: Outcomes
Response
Lapatinib (n = 116)
Placebo (n = 116)
HR (95% CI; P Value)
Median PFS, mos
4.6
5.1
1.1
( ; .62)
Response rate, % 14 8
P = .14
Median OS, mos
12.6
12.0
0.96
( ; .79)
OS, overall survival; PFS, progression-free survival.
No PFS or OS benefit with maintenance lapatinib, even in HER1/2 strongly positive subpopulation
No predictive or prognostic significance of high HER1/2 expression for PFS or OS in this population
Powles T, et al. ASCO Abstract 4505.

6. Maintenance Lapatinib in HER1/2-Positive Bladder Cancer: Safety
AE, %
Lapatinib (n = 64)
Placebo (n = 64)
Discontinuation due to AE 6 5
Grade 1/2
Grade 3/4
Diarrhea
57.8
9.4
25.0
Rash
53.1
4.7
26.6
Pain
48.4
Fatigue
29.7
35.9
Infection
23.4
6.3
20.3
3.1
Neuropathy
21.9
32.8
1.6
Nausea
17.2
AE, adverse event.
Powles T, et al. ASCO Abstract 4505.

7. Maintenance Lapatinib in HER1/2-Positive Bladder Cancer: Conclusions
Maintenance lapatinib did not provide clinical benefit after chemotherapy in HER1/2-positive bladder cancer
No benefit seen even in highest HER1/2 expression group
Progression on chemotherapy a much stronger factor in outcome than what regimen received
Lapatinib well tolerated but ineffective in this population
High HER1/2 expression does not have prognostic significance in bladder cancer
Short survival times in pts who responded to first-line chemotherapy emphasizes need for additional treatments
OS, overall survival; PFS, progression-free survival.
Powles T, et al. ASCO Abstract 4505.

8. Go Online for More CCO Coverage of ASCO 2015!
Short slidesets of all the key data
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Gastrointestinal cancers
Genitourinary cancer
Hematologic malignancies
Immunotherapy
Lung cancer
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