In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

A B S T R A C T PurposePrior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. MethodsMSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU ϩ levamisole or FU ϩ leucovorin; n ϭ 229) versus no postsurgical treatment (n ϭ 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P ϭ .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P ϭ .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n ϭ 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P ϭ .04). ConclusionPatient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.

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FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.).

These results confirm the efficacy and safety of GemOx, but this study failed to demonstrate a statistically significant advantage in terms of OS compared with Gem. Because GemOx is the first combined treatment to be superior to Gem alone in terms of clinical benefit, this promising regimen deserves further development.

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Background Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy. Methods In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Results A total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36–2.03, P < 0.001) and worse OS (HR, 2.01; 95% CI, 1.57–2.57; P < 0.001) compared to patients with low PIV. PIV outperformed the other IIBs in the GBR model and in the multivariable models. Conclusion PIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.

FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.