Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial

Florian Lordick, Yoon Koo Kang, Hyun Cheol Chung, Pamela Salman, Sang Cheul Oh, György Bodoky, Galina Kurteva, Constantin Volovat, Vladimir M. Moiseyenko, Vera Gorbunova, Joon Oh Park, Akira Sawaki, Ilhan Celik, Heiko Götte, Helena Melezínková, Markus Moehler

Research output: Contribution to journalArticle

485 Citations (Scopus)

Abstract

Background: Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods: In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m2 (on days 1-14) and intravenous cisplatin 80 mg/m2 (on day 1), with or without weekly cetuximab (400 mg/m2 initial infusion on day 1 followed by 250 mg/m2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings: Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2-5·5) compared with 5·6 months (5·1-5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92-1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3-4 adverse events, including grade 3-4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3-4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3-4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation: Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding: Merck KGaA.

Original languageEnglish
Pages (from-to)490-499
Number of pages10
JournalThe Lancet Oncology
Volume14
Issue number6
DOIs
Publication statusPublished - 2013 May 1

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Cisplatin
Stomach Neoplasms
Drug Therapy
Random Allocation
Exanthema
Disease-Free Survival
Stomach
Capecitabine
Cetuximab
Hand-Foot Syndrome
Esophagectomy
Hypokalemia
Acne Vulgaris
Advisory Committees
Gastrectomy
Adjuvant Chemotherapy
Esophageal Neoplasms
Neutropenia
Radio
Teaching Hospitals

ASJC Scopus subject areas

  • Oncology

Cite this

Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND) : A randomised, open-label phase 3 trial. / Lordick, Florian; Kang, Yoon Koo; Chung, Hyun Cheol; Salman, Pamela; Oh, Sang Cheul; Bodoky, György; Kurteva, Galina; Volovat, Constantin; Moiseyenko, Vladimir M.; Gorbunova, Vera; Park, Joon Oh; Sawaki, Akira; Celik, Ilhan; Götte, Heiko; Melezínková, Helena; Moehler, Markus.

In: The Lancet Oncology, Vol. 14, No. 6, 01.05.2013, p. 490-499.

Research output: Contribution to journalArticle

Lordick, F, Kang, YK, Chung, HC, Salman, P, Oh, SC, Bodoky, G, Kurteva, G, Volovat, C, Moiseyenko, VM, Gorbunova, V, Park, JO, Sawaki, A, Celik, I, Götte, H, Melezínková, H & Moehler, M 2013, 'Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial', The Lancet Oncology, vol. 14, no. 6, pp. 490-499. https://doi.org/10.1016/S1470-2045(13)70102-5
Lordick, Florian ; Kang, Yoon Koo ; Chung, Hyun Cheol ; Salman, Pamela ; Oh, Sang Cheul ; Bodoky, György ; Kurteva, Galina ; Volovat, Constantin ; Moiseyenko, Vladimir M. ; Gorbunova, Vera ; Park, Joon Oh ; Sawaki, Akira ; Celik, Ilhan ; Götte, Heiko ; Melezínková, Helena ; Moehler, Markus. / Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND) : A randomised, open-label phase 3 trial. In: The Lancet Oncology. 2013 ; Vol. 14, No. 6. pp. 490-499.
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T1 - Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND)

T2 - A randomised, open-label phase 3 trial

AU - Lordick, Florian

AU - Kang, Yoon Koo

AU - Chung, Hyun Cheol

AU - Salman, Pamela

AU - Oh, Sang Cheul

AU - Bodoky, György

AU - Kurteva, Galina

AU - Volovat, Constantin

AU - Moiseyenko, Vladimir M.

AU - Gorbunova, Vera

AU - Park, Joon Oh

AU - Sawaki, Akira

AU - Celik, Ilhan

AU - Götte, Heiko

AU - Melezínková, Helena

AU - Moehler, Markus

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Background: Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods: In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m2 (on days 1-14) and intravenous cisplatin 80 mg/m2 (on day 1), with or without weekly cetuximab (400 mg/m2 initial infusion on day 1 followed by 250 mg/m2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings: Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2-5·5) compared with 5·6 months (5·1-5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92-1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3-4 adverse events, including grade 3-4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3-4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3-4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation: Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding: Merck KGaA.

AB - Background: Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods: In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m2 (on days 1-14) and intravenous cisplatin 80 mg/m2 (on day 1), with or without weekly cetuximab (400 mg/m2 initial infusion on day 1 followed by 250 mg/m2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings: Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2-5·5) compared with 5·6 months (5·1-5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92-1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3-4 adverse events, including grade 3-4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3-4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3-4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation: Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding: Merck KGaA.

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