Chemotherapy (CT) plays a vital role as conversion treatment for initially unresectable or borderline resectable colorectal cancer (CRC). Targeted therapies are recommended with CT for conversion therapy; however, their role in conversion of initially unresectable tumours has not been elucidated. This meta-analysis evaluated the role of targeted therapies for conversion aimed at R0 resection in KRAS WT mCRC.
We conducted a literature search for randomized controlled trials (RCTs) in PubMed, Embase and Cochrane library evaluating the role of anti EGFR and anti VEGF as conversion therapies. A comparison was performed for anti-EGFR + CT vs. anti-VEGF + CT (Gp. A) and anti-EGFR + CT vs. CT (Gp. B). R0 resection rate and objective response rate (ORR) were the primary outcomes; with overall survival (OS), progression free survival (PFS) and safety evaluated as the secondary outcomes. Primary outcomes and safety were presented as relative risk (RR) and 95% confidence interval (CI), whereas survival was presented as hazard ratio (HR) and 95%CI.
We identified 8 RCTs from the potential 81 studies. In Gp. A, a fixed effects model was used for analysis; and showed that although non-significant, anti EGFR + CT had better R0 resection rate (RR 1.44, 95% CI 0.91,2.27; p = 0.1156; I2 = 0%) and ORR (RR 1.05, 95% CI 0.88, 1.24; p = 0.6039; I2 = 0%) compared with anti VEGF + CT. OS with anti EGFR + CT was significantly longer than anti VEGF + CT (HR: 0.64; CI 0.47, 0.86; p = 0.0036; I2 = 0%); however, PFS was numerically better in anti EGFR + CT. Compared with CT alone, anti EGFR + CT resulted in significantly higher R0 resection rate (RR 1.85, 95% CI 1.15,2.98; p = 0.0107; I2 = 57.16%) and ORR (RR 1.19, 95% CI 1.11, 1.28; p < 0.0001; I2 = 0%). In Gp. B, only PFS was significantly longer with anti EGFR + CT vs. CT (HR: 0.85; 95% CI 0.74, 0.98; p = 0.0015; I2 = 45.60%), and not OS. Safety evaluation showed anti EGFR + CT with significantly greater adverse events than CT alone (RR: 1.26; 95% CI: 1.18, 1.35; p < 0.0001).
In conclusion, anti EGFR + CT was an effective conversion therapy compared with anti VEGF + CT and CT in patients with initially unresectable mCRC; however, frequency of AEs was more with targeted therapy.
Clinical trial identification
Legal entity responsible for the study
Merck Serono Co. Ltd.
Merck Serono Co. Ltd.
All authors have declared no conflicts of interest.