Abstract | INTRODUCTION: 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.
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Authors | Tae Won Kim, Anneli Elme, Joon Oh Park, Anghel Adrian Udrea, Sun Young Kim, Joong Bae Ahn, Ricardo Villalobos Valencia, Srinivasan Krishnan, Nebojsa Manojlovic, Xuesong Guan, Catherine Lofton-Day, A Scott Jung, Eduard Vrdoljak |
Journal | Clinical colorectal cancer
(Clin Colorectal Cancer)
Vol. 17
Issue 3
Pg. 206-214
(09 2018)
ISSN: 1938-0674 [Electronic] United States |
PMID | 29703606
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- KRAS protein, human
- Oxaliplatin
- Panitumumab
- Irinotecan
- BRAF protein, human
- Proto-Oncogene Proteins B-raf
- Proto-Oncogene Proteins p21(ras)
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Topics |
- Adenocarcinoma
(genetics, mortality, pathology, therapy)
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology, therapeutic use)
- Colorectal Neoplasms
(genetics, mortality, pathology, therapy)
- Disease Progression
- Drug Resistance, Neoplasm
(genetics)
- Female
- Follow-Up Studies
- Humans
- Infusions, Intravenous
- Irinotecan
(pharmacology, therapeutic use)
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Mutation
- Oxaliplatin
(pharmacology, therapeutic use)
- Palliative Care
- Panitumumab
(pharmacology, therapeutic use)
- Progression-Free Survival
- Prospective Studies
- Proto-Oncogene Proteins B-raf
(genetics)
- Proto-Oncogene Proteins p21(ras)
(genetics)
- Tumor Burden
(drug effects)
- Young Adult
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