629P - Lapatinib versus lapatinib plus capecitabine as second-line treatment in Her2-overexpressing metastatic gastro-esophageal cancer (GC): A randomized...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Gastric Cancer
Translational Research
Presenter Sylvie Lorenzen
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors S. Lorenzen1, U. Helbig2, J. Riera-Knorrenschild3, G.M. Haag4, M. Pohl5, P.C. Thuss-Patience6, F. Bassermann1, F. Weißinger7, E. Schnoy8, K. Becker9, J. Rüschoff10, A. Eisenmenger11, I. Karapanagiotou-Schenkel11, F. Lordick12
  • 13rd Department Of Internal Medicine (hematology/medical Oncology), Klinikum rechts der Isar, Technische Universität München, 81667 - Munich/DE
  • 23rd Medical Department, Hematology And Oncology, Klinikum Braunschweig, Braunschweig/DE
  • 3Clinic For Hematology, Oncology And Immunology, Universitaetsklinikum Giessen und Marburg, Marburg/DE
  • 4Department Of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg/DE
  • 5Department Of Medicine, Knappschaftskrankenhaus, Ruhr University Bochum, Bochum/DE
  • 6Department Of Hematology, Oncology And Tumor Immunology, Virchow-Klinikum, Charité, Berlin, Berlin/DE
  • 7Department Of Medicine, Hematology, Oncology And Palliative Care, Evangelisches Krankenhaus, Bielefeld, Bielefeld/DE
  • 8Department Of Internal Medicine,, University Clinic Regensburg, Regensburg/DE
  • 9Onkologische Praxis, Lerchenfeld, DE-22081 - Hamburg/DE
  • 10Molecular Pathology, Targos, Kassel/DE
  • 11Nct Trial Center, National Center for Tumor Diseases, Heidelberg, Heidelberg/DE
  • 12University Cancer Center Leipzig, University of Leipzig, 04103 - Leipzig/DE

Abstract

Aim

Her2 amplification is present in a subgroup of gastroesophageal cancers (GCs). Her2 inhibition with Trastuzumab has shown to improve clinical outcomes in metastatic disease. Lapatinib ditosylate (LAP), a dual anti EGFR and anti Her2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in Her2 positive breast cancer. We aimed to study the activity of LAP in HER2 amplified GC.

Methods

Patients (pts) with Her2 positive (FISH ratio ≥2.0 or IHC3+ if ratio was between 1.8 and <2.0) advanced GC were randomly allocated 1:1 to receive LAP 1250 mg per day 1-21 plus capecitabine (CAP) 2000mg/m2 on days 1-14 of a 21-day cycle or LAP 1500 mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. Her2 status was assessed centrally. The primary endpoint was the objective response rate (complete or partial response) as assessed by the investigator using RECIST 1.1 criteria. We aimed to include 38 pts per arm to show an interesting response rate of >20% in either of the two arms.

Results

37 pts were enrolled (18 to LAP + CAP, 19 to LAP mono). Pts received a median of three treatment cycles. 10 pts in the LAP + CAP group (56%) and 7 pts in the LAP mono group (37%) had received prior Trastuzumab. Only two pts (11.1%; 95% CI: 1.37 – 34.7), both in the LAP + CAP arm, achieved an objective response. Therefore, the study was closed prematurely. Median time to progression was 42 (95% CI: 38 to 61) days in the LAP group and 83 (95% CI: 42 to 86) days in the LAP + CAP group (p = 0.07). The other secondary efficacy endpoints (progression-free [median 41 and 47 days] and overall survival [median values not yet mature]) were comparable in the two treatment groups. Rates of diarrhea (all grades) were higher with LAP + CAP (61%; 95% CI: 35 to 83) compared to 26% (95%CI 9 to 51) with LAP mono, while other adverse events were mostly similar between the groups (18[100%] vs. 17[90%]). Slightly more pts in the LAP-CAP group experienced serious adverse events (44 vs. 32%).

Conclusions

Lapatinib showed insufficient activity, especially as monotherapy, in HER2 amplified pretreated advanced GC. This led to premature study termination. The safety profile of LAP or LAP + CAP was as expected with some more toxicity in the combination arm.

Disclosure

P.C. Thuss-Patience: Research support by GSK; F. Lordick: GSK. All other authors have declared no conflicts of interest.