Markus Moehler1,2, Arno Schad3, Annett Maderer4, Ajlan Atasoy5, Murielle E Mauer5, Carmela Caballero5, Thomas Thomaidis4, Jestinah M Mahachie John5, Istvan Lang6, Eric Van Cutsem7, João Freire8, Manfred P Lutz9, Arnaud Roth10. 1. I. Department of Internal Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany. markus.moehler@unimedizin-mainz.de. 2. I. Department of Internal Medicine, University Medical Center Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. markus.moehler@unimedizin-mainz.de. 3. Institute of Pathology, Johannes Gutenberg University of Mainz, Mainz, Germany. 4. I. Department of Internal Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany. 5. EORTC Headquarters, Brussels, Belgium. 6. National Institute of Oncology, Budapest, Hungary. 7. University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium. 8. Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal. 9. Department of Internal Medicine, Caritasklinikum St. Theresia, Saarbrücken, Germany. 10. Department of Oncosurgery, University of Geneva, Geneva, Switzerland.
Abstract
PURPOSE:HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS:Tumors from chemotherapy-naïve patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. RESULTS: 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu-: by FISH/+ by IHC, n = 5) and 3 (HER2neu-/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37-1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30-2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35-2.27). There were no safety concerns. CONCLUSIONS: Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.
RCT Entities:
PURPOSE:HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS: Tumors from chemotherapy-naïve patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. RESULTS: 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu-: by FISH/+ by IHC, n = 5) and 3 (HER2neu-/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37-1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30-2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35-2.27). There were no safety concerns. CONCLUSIONS: Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.
Authors: Haeseong Park; Ramon U Jin; Andrea Wang-Gillam; Rama Suresh; Caron Rigden; Manik Amin; Benjamin R Tan; Katrina S Pedersen; Kian-Huat Lim; Nikolaos A Trikalinos; Abhilasha Acharya; Megan L Copsey; Katherine A Navo; Ashley E Morton; Feng Gao; A Craig Lockhart Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777