title: Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study.
abstract: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed.
  
  
  
  APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated.
  
  
  
  In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations.
  
  
  
  The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.
authors: National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
authors: Ann-Lii
authors: AL
authors: Cheng
authors: San Juan de Dios Hospital, Pasay City, Philippines.
authors: Gerardo
authors: G
authors: Cornelio
authors: Peking University Cancer Hospital and Institute, Beijing, China.
authors: Lin
authors: L
authors: Shen
authors: Queen Elizabeth Hospital, Woodville, Australia.
authors: Timothy
authors: T
authors: Price
authors: Chang Gung Memorial Hospital-LinKou, Taoyuan, Taiwan.
authors: Tsai-Sheng
authors: TS
authors: Yang
authors: Chonnam National University Hwasun Hospital, Hwasun-eup, South Korea.
authors: Ik Joo
authors: IJ
authors: Chung
authors: The General Hospital of the People's Liberation Army, Beijing, China.
authors: Guang-Hai
authors: GH
authors: Dai
authors: Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Jen-Kou
authors: JK
authors: Lin
authors: All India Institute of Medical Sciences, New Delhi, India.
authors: Atul
authors: A
authors: Sharma
authors: National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
authors: Kun-Huei
authors: KH
authors: Yeh
authors: Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, New Territories, Hong Kong, China.
authors: Brigette
authors: B
authors: Ma
authors: Mount Miriam Cancer Hospital, Penang, Malaysia.
authors: Adel
authors: A
authors: Zaatar
authors: Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Zhongzhen
authors: Z
authors: Guan
authors: The Aga Khan University and Hospital, Karachi, Pakistan.
authors: Nehal
authors: N
authors: Masood
authors: Ramathibodi Hospital, Siriraj Hospital, Bangkok, Thailand.
authors: Vichien
authors: V
authors: Srimuninnimit
authors: Queen Mary Hospital, Pok Fu Lam, Hong Kong.
authors: Thomas
authors: T
authors: Yau
authors: Western Hospital, Australia.
authors: Peter
authors: P
authors: Gibbs
authors: Qilu Hospital of Shandong University, Shandong, China.
authors: Xiuwen
authors: X
authors: Wang
authors: Rajiv Gandhi Cancer Institute & Research Centre, Rohini, New Delhi, India.
authors: Dinesh Chandra
authors: DC
authors: Doval
authors: The Catholic University of Korea: Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors: Seung-Taek
authors: ST
authors: Oh
authors: The Catholic University of Korea: St. Vincent's Hospital, Paldal-Gu, Suwon, Republic of Korea.
authors: Byoung Yong
authors: BY
authors: Shim
authors: St Luke's Medical Center, Philippines.
authors: Charity
authors: C
authors: Gorospe
authors: Taichung Veterans General Hospital, Taichung City, Taiwan.
authors: Hwei-Ming
authors: HM
authors: Wang
authors: Ramathibodi Hospital, Siriraj Hospital, Bangkok, Thailand.
authors: Ekaphop
authors: E
authors: Sirachainan
authors: Gold Coast Hospital, Southport, Queensland, Australia.
authors: Andrew
authors: A
authors: Hill
authors: Ajou University Hospital, Yeongtong-gu, Suwon, Republic of Korea.
authors: Kwang Wook
authors: KW
authors: Suh
authors: Merck KGaA, Darmstadt, Germany.
authors: Frank
authors: F
authors: Beier
authors: Merck Ltd, Mumbai, India.
authors: Sudipto
authors: S
authors: Chatterjee
authors: National University Cancer Institute, Singapore.
authors: Robert
authors: R
authors: Lim
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Depth of response; Dosing schedule; Early tumor shrinkage; Erbitux; mCRC