Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer according to HER2neu and EGFR status

a randomized placebo-controlled phase II study (EORTC 40071)

the EORTC Gastrointestinal Tract Cancer Group

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Stomach Neoplasms
Fluorescence In Situ Hybridization
Placebos
Fluorescence
Immunohistochemistry
Stomach
Carcinoma
Disease-Free Survival
Therapeutics
Safety
Epirubicin
Chemotherapy
Survival
Amplification
Tumors
Research Personnel
lapatinib
Drug Therapy
Population
Neoplasms

Keywords

  • Advanced gastric cancer
  • EGFR
  • First-line
  • HER2neu
  • Lapatinib
  • Placebo-controlled

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

@article{dacdc4ab91134436b682241b7432026e,
title = "Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer according to HER2neu and EGFR status: a randomized placebo-controlled phase II study (EORTC 40071)",
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-na{\"i}ve 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.",
keywords = "Advanced gastric cancer, EGFR, First-line, HER2neu, Lapatinib, Placebo-controlled",
author = "{the EORTC Gastrointestinal Tract Cancer Group} and Markus Moehler and Arno Schad and Annett Maderer and Ajlan Atasoy and Mauer, {Murielle E.} and Carmela Caballero and Thomas Thomaidis and John, {Jestinah M.Mahachie} and I. L{\'a}ng and {Van Cutsem}, Eric and Jo{\~a}o Freire and Lutz, {Manfred P.} and Arnaud Roth",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00280-018-3667-8",
language = "English",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer according to HER2neu and EGFR status

T2 - a randomized placebo-controlled phase II study (EORTC 40071)

AU - the EORTC Gastrointestinal Tract Cancer Group

AU - Moehler, Markus

AU - Schad, Arno

AU - Maderer, Annett

AU - Atasoy, Ajlan

AU - Mauer, Murielle E.

AU - Caballero, Carmela

AU - Thomaidis, Thomas

AU - John, Jestinah M.Mahachie

AU - Láng, I.

AU - Van Cutsem, Eric

AU - Freire, João

AU - Lutz, Manfred P.

AU - Roth, Arnaud

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Advanced gastric cancer

KW - EGFR

KW - First-line

KW - HER2neu

KW - Lapatinib

KW - Placebo-controlled

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U2 - 10.1007/s00280-018-3667-8

DO - 10.1007/s00280-018-3667-8

M3 - Article

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

ER -