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.

Autor: Kim TW; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: twkimmd@amc.seoul.kr., Elme A; Department of Gastroenterology, Oncology, North Estonia Medical Centre Foundation, Tallinn, Estonia., Park JO; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Udrea AA; SC MEDISPROF SRL, Cluj-Napoca, Romania., Kim SY; Division of Hemato-Oncology, National Cancer Center, Goyang, Gyeonggi-do, South Korea., Ahn JB; Department of Internal Medicine, Yonsei University Health System Severance Hospital, Seoul, South Korea., Valencia RV; Department of Medical Oncology, Hospital de Oncologia, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico., Krishnan S; Department of Clinical Research, Dr Rai Memorial Medical Centre, Chennai, Tamil Nadu, India., Manojlovic N; Department of Digestive Oncology, Clinic for Gastroenterology and Hepatology of Military Medical Academy of Serbia, Belgrade, Serbia., Guan X; Amgen Inc, Thousand Oaks, CA., Lofton-Day C; Amgen Inc, Thousand Oaks, CA., Jung AS; Amgen Inc, Thousand Oaks, CA., Vrdoljak E; Department of Oncology, Center of Oncology, Clinical Hospital Center Split, Split, Croatia.
Jazyk: angličtina
Zdroj: Clinical colorectal cancer [Clin Colorectal Cancer] 2018 Sep; Vol. 17 (3), pp. 206-214. Date of Electronic Publication: 2018 Mar 21.
DOI: 10.1016/j.clcc.2018.03.008
Abstrakt: 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.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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