title: Oxaliplatin-based chemotherapy is more beneficial in KRAS mutant than in KRAS wild-type metastatic colorectal cancer patients.
abstract: To identify better regimens in currently available chemotherapy would be beneficial to KRAS mutant metastatic colorectal cancer (mCRC) patients because they have fewer treatment options than KRAS wild-type mCRC patients. Clinicopathologic features and overall survival (OS) of KRAS mutant and wild-type mCRC patients who had used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens were compared to those who had never-used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens respectively. Between 2007 and 2012, a total of 394 mCRC patients, in whom 169 KRAS mutant and 225 KRAS wild-type, were enrolled. In KRAS mutant patients who had used oxaliplatin-based regimens (N = 131), the OS was significantly longer than that in KRAS mutant patients who had never-used oxaliplatin-based regimens (N = 38). The OS was 28.8 months [95% confidence interval (CI): 23.2-34.4] in KRAS mutant patients who had used oxaliplatin-based regimens versus 17.8 months [95% CI: 6.5-29.1] in KRAS mutant patients who had never-used oxaliplatin-based regimens (P = 0.026). Notably, OS in KRAS wild-type mCRC patients who had used oxaliplatin-based regimens (N = 185) was not significantly longer than that in KRAS wild-type mCRC patients who had never-used oxaliplatin-based regimens (N = 40) (P = 0.25). Furthermore, the OS in KRAS mutant patients who had used either irinotecan-based, bevacizumab-based or cetuximab-based regimens was not significantly different than that in KRAS mutant patients who had never-used either irinotecan-based, bevacizumab-based or cetuximab-based regimens respectively. In multivariate analyses, patients who had used oxaliplatin-based regimens remains an independent prognostic factor for longer OS in KRAS mutant mCRC patients. In conclusion, oxaliplatin-based regimens are more beneficial in KRAS mutant than in KRAS wild-type mCRC patients.
authors: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yu-Lin
authors: YL
authors: Lin
authors: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan ; Department of Hemato-Oncology, E-da Hospital, Kaohsiung City, Taiwan.
authors: Yi-Hsin
authors: YH
authors: Liang
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Jia-Huei
authors: JH
authors: Tsai
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Jau-Yu
authors: JY
authors: Liau
authors: Division of Colorectal Surgery, National Taiwan University Hospital, Taipei, Taiwan ; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: Jin-Tung
authors: JT
authors: Liang
authors: Division of Colorectal Surgery, National Taiwan University Hospital, Taipei, Taiwan ; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: Been-Ren
authors: BR
authors: Lin
authors: Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
authors: Ji-Shiang
authors: JS
authors: Hung
authors: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Liang-In
authors: LI
authors: Lin
authors: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors: Li-Hui
authors: LH
authors: Tseng
authors: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yih-Leong
authors: YL
authors: Chang
authors: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Kun-Huei
authors: KH
authors: Yeh
authors: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan ; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Ann-Lii
authors: AL
authors: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins