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 Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
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.