525P - A phase III study of EAGLE comparing two doses of bevacizumab combined with FOLFIRI in the second-line setting after first-line treatment with beva...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Pathology/Molecular Biology
Presenter Yoshinori Munemoto
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors Y. Munemoto1, S. Iwamoto2, T. Takahashi3, H. Tamagawa4, M. Nakamura5, T. Kato6, T. Hata7, T. Denda8, Y. Morita9, M. Inukai10, K. Kunieda11, N. Nagata12, K. Kurachi13, K. Ina14, M. Oshiro15, T. Shimoyama16, H. Baba17, K. Oba18, J. Sakamoto19, H. Mishima20
  • 1Surgery, FUKUI PREFECTURE-SAISEIKAI HOSPITAL, 918-8503 - Fukui/JP
  • 2Surgery, Kansai Medical University School Hirakata Hospital, 573-1010 - Osaka/JP
  • 3Surgical Oncology, Gifu University Graduate School of Medicine, 500-1194 - Gifu/JP
  • 4Surgery, Otemae Hospital, Osaka/JP
  • 5Cancer Center, Aizawa Hospital, 390-8510 - Matsumoto/JP
  • 6Surgery, Kansai Rosai Hospital, 660-8511 - Amagasaki/JP
  • 7Surgery, Osaka University Graduate School of Medicine, 565-0871 - Suita/JP
  • 8Gastroenterology, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 9Radiology, Kobe medical center, 654-0155 - Kobe/JP
  • 10Integrated Medicine, Kagawa University Hospital, 761-0793 - Kita-gun/JP
  • 11Surgery, Gifu Prefectual General Medical Center, 500-8226 - GIfu/JP
  • 12Surgery, Kitakyusyu General Hospital, 800-0295 - Kitakyusyu/JP
  • 13Surgery, Hamamatsu University school of Medicine, Sizuoka/JP
  • 14Medical Oncology, Nagoya Memorial Hospital, Nagoya/JP
  • 15Surgery, Toho University Sakura Medical Center, Sakura/JP
  • 16Chemotherapy, Cancer and Infectious diseases center Komagome hospital, 113-0021 - Bunkyo-ku, Tokyo/JP
  • 17Gastroenterological Surgery, Kumamoto University, JP-860-8556 - Kumamoto/JP
  • 18Translational Research And Clinical Trial Center, Hokkaido University Hospital, Sapporo/JP
  • 19Director, Tokai Central Hospital, Kagamigahara/JP
  • 20Clinical Oncology, Aichi Medical University, 480-1195 - Nagakute/JP

Abstract

Aim

ML18147 showed continued bevcizumab(BEV) with second-line chmotherapy for patients with metastatic colorectal cancer (mCRC) treated with bev plus standard first-line chemotherapy, represents an option for patients with mCRC independent of KRS status. EAGLE study evaluted two doses of bev (10 mg/kg or 5 mg/kg) combined with FOLFIRI in the second-line setting after first-line treatmet with bev plus oxaliplatin-based therapy. Bev 10 mg/kg plus FOLFIRI as second-line treatment did not prolong pogression-free survival (PFS) compared with bev 5mg/kg plus FOLFIRI in patients with mCRC.

Methods

Outcomes according to tumor KRAS status were evaluated as an exploratory analysis. KRAS data were collected from each institution. Survival analyses using Cox regression and Log-rank test were conducted by subgroups of the KRAS status.

Results

Of 387 patients, 326 (84%) had KRAS data; 164 (50%) had KRAS wild-type tumors and 162 (50%) had mutant KRAS tumors. The median PFS was 7.1 months for bev 10 mg/kg and 5.9 months for bev 5 mg/kg (P = 0.568; HR = 1.04; 95% confidence interval (CI) : 0.76-1.43) for wild-type KRAS and 5.6 months fo bev 10 mg/kg and 6.5 months for bev 5mg/kg, respectively ( P = 0.89; HR = 1.10; 95% CI: 0.80-1.51) for mutant KRAS. The P value of test for treatment-subgroup inteaction was 0.956. The median overall survival (OS) was 17.9 months for bev 10mg/kg and 15.5 months for bev 5 mg/kg, respectvely (P = 0.244; HR = 0.80; 95% CI : 0.55-1.17) for wild-tpe KRAS and 15.9 months for bev 10 mg/kg versus 17.7 months for bev 5 mg/kg, respectivly (P = 0.312; HR = 1.21; 95% CI 0.84-1.74) for mutant KRAS.

Conclusions

Although possible differences of treatment effect between bev 5 mg/kg and 10 mg/kg groups were observed for patients with wild-type KRAS, these results revealed bev 10mg/kg plus FOLFIRI as second-line treatment did not prolong PFS compared with bev 5 mg/kg plus FOLFIRI in patients with mCRC depending on KRAS status.

Disclosure

S. Iwamoto: I have honoraria to disclose from Chugai, MerckSerono; T. Takahashi: I have honoraria to disclose from Chugai, Takeda, Taiho, MerckSerono. Bristol-Meyers Squibb; T. Kato: I have honoraria to disclose from Chugai, Yakult; T. Denda: I have honoraria to disclose from Taiho, Lilly, Sanofi; H. Baba: I have honoraria to disclose from Chugai, Takeda, Taiho; H. Mishima: I have honoraria to disclose from Chugai, Takeda, Taiho, Yakult. Ono, Tsumura, MerckSerono. Bristol-Meyers Squibb, Medicon. All other authors have declared no conflicts of interest.