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 twkimmd@amc.seoul.kr.
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.
ABSTRACT
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.
keyword
Anti-EGFR therapy; Biomarkers; Gastrointestinal cancer; Randomized controlled trial; Treatment outcome
링크

주제코드
주제명(Target field)
연구대상(Population)
연구참여(Sample size)
대상성별(Gender)
질병특성(Condition Category)
연구환경(Setting)
연구설계(Study Design)
연구기간(Period)
중재방법(Intervention Type)
중재명칭(Intervention Name)
키워드(Keyword)
유효성결과(Recomendation)
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)
출판년도(Year)
참여저자수(Authors)
대표저자
DOI
10.1016/j.clcc.2018.03.008.
KCD코드
ICD 03
건강보험코드