Tomomi Kashiwada

Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

This article compares the efficacy between regorafenib and trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy, who had access to both drugs, to determine whether a further prospective comparative trial should be conducted.

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

KRAS mutations have been recognized as predictive markers of primary resistance to anti-EGFR-antibodies in colorectal cancer patients. In addition, newly detected KRAS mutations have been reported to be related with acquired resistance to chemotherapy containing anti-EGFR antibody. Considering this evidence, monitoring of KRAS mutations is indispensable for making treatment decisions, and the method should be non-invasive allowing repeated examinations. Recently, we established a novel automated sensitive detection system for KRAS mutations, named mutation-biased PCR quenching probe system (MBP-QP). The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies. The detection limit of MBP-QP using a control plasmid containing KRAS mutations was 1–9 copies, and 0.05–0.3% mutant plasmid was detectable in a mixture of wild type and mutants. One-hundred twenty colorectal cancer patients were genotyped for KRAS mutations with MBP-QP as well as polymerase chain reaction reverse sequence-specific oligonucleotide (PCR-rSSO), which has already been applied to cancer tissue samples in the clinical setting. Concordance rates between plasma DNA and cancer tissues were 68% with MBP-QP and 66% with PCR-rSSO, indicating that these systems are equivalent in terms of detecting KRAS mutations with plasma DNA. KRAS mutations in plasma DNA were frequently observed in systemic metastatic cancer patients, and in three patients KRAS mutations appeared after chemotherapy containing anti-EGFR antibody. A prospective study is needed for clarifying whether KRAS mutations detected in plasma DNA are predictive markers of treatment efficacy with anti-EGFR antibody.

Role of Predictive Value of the Modified Glasgow Prognostic Score for Later-line Chemotherapy in Patients With Metastatic Colorectal Cancer

Micro‐Abstract The survival and safety of patients with metastatic colorectal cancer treated with trifluridine/tipiracil or regorafenib as later‐line chemotherapy were retrospectively examined according to the modified Glasgow Prognostic Score (mGPS). Overall and progression‐free survival were strongly correlated with mGPS in all patients. The frequency of adverse events was generally similar in each mGPS group. Background Assessment of patient factors is essential for selecting later‐line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated. Patients and Methods A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS‐102 as Salvage‐line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later‐line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C‐reactive protein, and compared. Results The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2‐11.6 months), 6.5 months (95% CI, 5.3‐7.1 months), and 3.9 months (95% CI, 3.3‐4.9 months), respectively. The median progression‐free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1‐3.0 months), 2.0 months (95% CI, 1.9‐2.3 months), and 1.7 months (95% CI, 1.4‐1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93‐2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01‐2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS. Conclusions The mGPS before later‐line chemotherapy is strongly correlated with survival in patients with mCRC.