Tae Won Kim1, Anneli Elme2, Joon Oh Park3, Anghel Adrian Udrea4, Sun Young Kim5, Joong Bae Ahn6, Ricardo Villalobos Valencia7, Srinivasan Krishnan8, Nebojsa Manojlovic9, Xuesong Guan10, Catherine Lofton-Day10, A Scott Jung10, Eduard Vrdoljak11. 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: twkimmd@amc.seoul.kr. 2. Department of Gastroenterology, Oncology, North Estonia Medical Centre Foundation, Tallinn, Estonia. 3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 4. SC MEDISPROF SRL, Cluj-Napoca, Romania. 5. Division of Hemato-Oncology, National Cancer Center, Goyang, Gyeonggi-do, South Korea. 6. Department of Internal Medicine, Yonsei University Health System Severance Hospital, Seoul, South Korea. 7. Department of Medical Oncology, Hospital de Oncologia, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico. 8. Department of Clinical Research, Dr Rai Memorial Medical Centre, Chennai, Tamil Nadu, India. 9. Department of Digestive Oncology, Clinic for Gastroenterology and Hepatology of Military Medical Academy of Serbia, Belgrade, Serbia. 10. Amgen Inc, Thousand Oaks, CA. 11. 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.
RCT Entities:
INTRODUCTION:Tumorratsarcoma 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 ratsarcoma 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.
Authors: Alexa B Schrock; Jessica K Lee; Jaideep Sandhu; Russell Madison; Cheryl Cho-Phan; Jeremy W Snider; Emily Castellanos; Jeffrey M Venstrom; Marwan Fakih Journal: Oncologist Date: 2021-02-10