Final Analysis of Outcomes and RAS/BRAF Status in a Randomized Phase 3 Study of Panitumumab and Best Supportive Care in Chemorefractory Wild Type KRAS Metastatic Colorectal Cancer.

Kim, Tae Won; Elme, Anneli; Park, Joon Oh; Udrea, Anghel Adrian; Kim, Sun Young; Ahn, Joong Bae; Valencia, Ricardo Villalobos; Krishnan, Srinivasan; Manojlovic, Nebojsa; Guan, Xuesong; Lofton-Day, Catherine; Jung, A Scott; Vrdoljak, Eduard
Clinical colorectal cancer
2018Mar ; 11 ( 3 ) :.
저자 상세정보
Kim, Tae Won - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address
Elme, Anneli - Department of Gastroenterology, Oncology, North Estonia Medical Centre Foundation, Tallinn, Estonia.
Park, Joon Oh - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Udrea, Anghel Adrian - SC MEDISPROF SRL, Cluj-Napoca, Romania.
Kim, Sun Young - Division of Hemato-Oncology, National Cancer Center, Goyang, Gyeonggi-do, South Korea.
Ahn, Joong Bae - Department of Internal Medicine, Yonsei University Health System Severance Hospital, Seoul, South Korea.
Valencia, Ricardo Villalobos - Department of Medical Oncology, Hospital de Oncologia, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
Krishnan, Srinivasan - Department of Clinical Research, Dr Rai Memorial Medical Centre, Chennai, Tamil Nadu, India.
Manojlovic, Nebojsa - Department of Digestive Oncology, Clinic for Gastroenterology and Hepatology of Military Medical Academy of Serbia, Belgrade, Serbia.
Guan, Xuesong - Amgen Inc, Thousand Oaks, CA.
Lofton-Day, Catherine - Amgen Inc, Thousand Oaks, CA.
Jung, A Scott - Amgen Inc, Thousand Oaks, CA.
Vrdoljak, Eduard - Department of Oncology, Center of Oncology, Clinical Hospital Center Split, Split, Croatia.
INTRODUCTION: Tumor rat sarcoma gene (RAS) status is a negative predictive biomarker for anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). We analyzed outcomes according to RAS and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutational status, and evaluated early tumor shrinkage (ETS) and depth of response (DpR) for patients with wild type RAS. PATIENTS AND

METHODS: Patients with confirmed metastatic colon or rectum adenocarcinoma, wild type Kristen rat sarcoma gene tumor exon 2 status, clinical/radiologic disease progression or toxicity during irinotecan or oxaliplatin treatment, and no previous anti-EGFR therapy were randomized 1:1 to receive best supportive care (BSC) with or without panitumumab (6.0 mg/kg, intravenously, on day 1 of each 14-day cycle) in this open-label, multicenter, phase III study (20100007). RAS and BRAF mutation status were determined using Sanger sequencing. ETS was evaluated as maximum percentage change from baseline to week 8; DpR was calculated as the percentage change for tumor shrinkage at nadir versus baseline.

RESULTS: Overall, 270 patients had RAS wild type mCRC (panitumumab with BSC, n?= 142; BSC, n?= 128). For patients with wild type RAS tumors, median overall survival (OS; hazard ratio [HR], 0.72; P?= .015) and progression-free survival (PFS; HR, 0.45; P?< .0001) were improved with panitumumab with BSC versus BSC. Similar improvements were seen for patients with wild type RAS, and wild type BRAF tumors (OS: HR, 0.75; P?= .04; PFS: HR, 0.45; P?< .0001). Median DpR was 16.9% for the evaluable panitumumab with BSC wild type RAS population. Overall, 69.5% experienced any type of tumor shrinkage at week 8; 38.2% experienced???20% shrinkage. Similar improvements in OS and PFS were seen with stratification according to ETS. CONCLUSION: This analysis showed that panitumumab improved outcomes in wild type RAS mCRC and indicated that ETS and DpR could be used as additional efficacy markers. CI - Copyright ??2018 The Authors. Published by Elsevier Inc. All rights reserved.
Anti-EGFR therapy; Biomarkers; Gastrointestinal cancer; Randomized controlled trial; Treatment outcome

주제명(Target field)
연구참여(Sample size)
질병특성(Condition Category)
연구설계(Study Design)
중재방법(Intervention Type)
중재명칭(Intervention Name)
Panitumumab improved outcomes in patients with wild type RAS , consistent with the primary analysis, and in patients with in wild type RAS , wild type BRAF mCRC.
연구비지원(Fund Source)
근거수준평가(Evidence Hierarchy)
ICD 03