Randomized trials of adjuvant 5-FU-based systemic chemotherapy failed to demonstrate benefit after resection of liver metastases. However FOLFOX or XELOX are widely employed in clinical practice as adjuvant chemotherapy in Stage IV CRC as well as Stage III due to its high recurrence rate. Patient selection by using appropriate biomarker would be needed. RAS/PIK3CA/BRAF mutation would have a key role on mCRC treatment. We assessed the significance of RAS/PIK3CA/BRAF mutational status in adjuvant treatment for Stage IV CRC.
Eighty-eight patients received adjuvant chemotherapy after R0 resection for StageIV CRC in our institute between May 2007 and June 2013. Of 88 patients, we could obtained 78 specimens to be analyze RAS/PIK3CA/BRAF mutational status. The present study assessed retrospectively association between relapse-free survival (RFS) and mutational status. Gene mutations were detected by using multiplex assay (Luminex®) or invader method.
Baseline characteristics were as follows (N = 78): median age, 61; male/female, 44/34; ECOG PS0, all; right-sided colon (RCC) /left-sided colon and rectum (LCRC), 10/68; previous adjuvant chemotherapy for Stage III yes/no, 18/60; liver mets/extra-liver mets, 45/32; solitary metastasis/multiple metastases, 32/46. Patients with KRAS (ex.2) wild-type were 44, RAS wild-type were 34 and all wild-type (RAS/PIK3CA/BRAF) were 32. Patients with PIK3CA and BRAF were only 1 and 3 respectively. Median RFS was 60.8 months and OS not assessable. RFS at 3 years was 54.0%. In univariate analysis, multiple metastases and previous adjuvant chemotherapy had statistically significant association with shorter RFS. There was slight difference between KRAS (ex.2) wild and mutant in RFS, compared with log-rank test but the difference between RAS wild and mutant was not observed. Multivariate analysis revealed previous adjuvant chemotherapy as negative predictive factor for relapse.
Narrowing treatment subjects to all wild-type populations of RAS/PIK3CA/BRAF status might not contribute to enrich patients with benefit from adjuvant chemotherapy in Stage IV CRC.
Clinical trial identification
retrospective cohort study
T. Azuma: Toppan Printing. All other authors have declared no conflicts of interest.