Chemotherapy and Targeted Therapy Strategies in Patients with Unresectable or Borderline Resectable Metastatic Colorectal Cancer: Evidence for a Lack of Focus on Resection Rates

Abstract

Abstract Background and aims Chemotherapy (CTx) with targeted therapy (TT) have increased the overall response rate (ORR) and improved survival in unresectable or borderline resectable metastatic colorectal cancer (mCRC). However, the resection rate is an endpoint with often suboptimal expert involvement. The aim was to investigate whether the improvements in ORR have translated to improved resection rates (RR). Study design A systematic literature search was performed using the PICO process. Statistical analysis Odds ratios, and 95% confidence intervals (OR, 95% CI) were analyzed for ORR and RR using dichotomous values with the Mantel-Haenszel method. Progression-free survival (PFS) and overall survival (OS) were analyzed using the inverse-variance method and displayed as hazard ratios and 95% confidence intervals (HR, 95% CI). Results The literature search returned 469 records. Sixteen articles with 5724 patients were selected for analysis. The qualitative analysis revealed low and moderate risk of bias endpoints. Higher ORR was observed with CTx + TT versus CTx only (OR: 0.62 [95% CI 0.45; 0.82], p = 0.002) and with triplet CTx + TT versus doublet CTx + TT (OR: 0.61 [95% CI 0.46; 0.81], p < 0.001). PFS and OS were improved by use of TT (HR: 0.68–0.84; p < 0.001 to 0.04). The overall RR was low (< 15%) and did not improve in the same way as the other endpoints. Conclusion The ORR and survival rates in unresectable and borderline resectable mCRC were improved by modern CTx and TT that did not translate into higher RR, mostly due to the lack of expert involvement.