LBA3 - Cetuximab in combination with capecitabine and cisplatin as first-line treatment in advanced gastric cancer: Randomized controlled phase III EXPAND...

Date 30 September 2012
Event ESMO Congress 2012
Session Presidential Symposium I
Topics Anticancer agents
Gastric Cancer
Therapy
Biological therapy
Presenter Florian Lordick
Authors F. Lordick1, G. Bodoky2, H. Chung3, G. Kurteva4, Y. Kang5, S.C. Oh6, P. Salman7, H. Goette8, H. Melezinkova9, M. Moehler10
  • 1University Cancer Center Leipzig, Klinikum Braunschweig, 38114 - Braunschweig/DE
  • 2Department Of Oncology, St.László Hospital, Budapest/HU
  • 3Division Of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 4Center Of Oncology, Specialized Hospital for Active Treatment, Sofia/BG
  • 5Dept. Of Oncology, Asan Medical Center, KR-138-736 - Seoul/KR
  • 6Guro Hospital, Korea University, Seoul/KR
  • 7Division Of Medical Oncology And Hematology,, Fundación Arturo López Pérez, Santiago/CL
  • 8Global Biostatistics, Merck KGaA, Darmstadt/DE
  • 9Global Clinical Development Centre, Merck KGaA, Darmstadt/DE
  • 10I Medical Department, University Medical Center of the Johannes Gutenberg University Mainz, DE-55131 - Mainz/DE

 

Abstract

Background: There is a high unmet clinical need for more efficacious treatment in advanced gastric cancer, which has a poor prognosis. In phase II studies, cetuximab, an EGFR antibody, + first-line fluoropyrimidine with irinotecan or platinum compounds showed promising activity. This open-label, randomized, controlled phase III study (EudraCT No: 2007-004219-75) investigated capecitabine and cisplatin +/- cetuximab in gastric and gastroesophageal junction cancer.

Methods: Patients (pts) were randomized (1:1) to 3-week cycles of twice daily (days 1-15) capecitabine (X, Xeloda®) 1000 mg/m2 and iv cisplatin (P) 80 mg/m2 (day 1) + weekly cetuximab (day 1) 400 mg/m2 initial infusion followed by 250 mg/m2/week thereafter, or XP alone. The primary endpoint was progression-free survival (PFS) assessed by blinded independent review committee (IRC). Secondary endpoints included overall survival (OS), best overall response (IRC) and safety.

Results: Between June 2008 and December 2010, 904 pts from 25 countries were randomized; 455 to XP + cetuximab and 449 to XP alone. Most were male (74%), had stomach cancer (83%) and metastatic disease (97%). Baseline characteristics were balanced between treatment arms. Median duration of cetuximab treatment was 14.9 weeks with relative dose intensity =80% received by 88% of pts. Exposure to X and P was similar between treatment arms. PFS, OS and best overall response were similar between the treatment arms (Table) with comparable results for PFS and OS across subgroups. More grade 3/4 and serious adverse events were found in the XP + cetuximab vs XP arm (Table). Safety profiles were consistent with those known for these agents.

Conclusions: XP + cetuximab showed no benefit compared with XP alone in the first-line treatment of advanced gastric cancer. Further classification of this heterogeneous disease may be required before advances in patient treatment are to be made.

Table

XP + cetuximab

XP

Efficacy analysisa

Number of patients

455

449

PFS (IRC)

Median, months [95% CI]

4.4 [4.2–5.5]

5.6 [5.1–5.7]

Stratified HR [95% CI]

1.091 [0.920–1.292]

Stratified log-rank p value

0.3158

OS

Median, months [95% CI]

9.4 [8.3–10.6]

10.7 [9.4–11.3]

Stratified HR [95% CI]

1.004 [0.866–1.165]

Stratified log-rank p value

0.9547

Best overall response (IRC)

ORRb, % [95% CI]

30 [26–34]

29 [25–34]

Summary of safety analysis

Number of patients

446

436

Any AEs, %

100

99

Grade 3-4 AEs, %

83

77

Any serious AEs, %

54

45

aStratification factors were disease status, prior esophago-/gastrectomy, prior neo adjuvant/radiochemotherapy. bORR = complete response + partial response.
AE, adverse event; CI, confidence interval; HR, hazard ratio; IRC, independent review committee; ORR, best overall response rate; OS, overall survival; PFS, progression-free survival.