TABLE 4.
Anti-EGFR Therapy Plus Doublet Chemotherapy Versus Anti-VEGF Therapy Plus Doublet Chemotherapy for First-Line Treatment of RS or LS RAS Wild-Type Metastatic Colorectal Cancer13
| Outcome, Time Frame | Study Results | Absolute Effect Estimates | Quality of Evidence (heterogeneity) | Plain Language Summary | |
|---|---|---|---|---|---|
| Anti-VEGF + Doublet Chemotherapy | Anti-EGFR + Doublet Chemotherapy | ||||
| OS (left-sided tumors), 24 months | HR, 0.71 (95% CI, 0.58 to 0.85) (689 patients in three studies) | 400 deaths48 per 1,000 | 304 deaths per 1,000 | Moderatea; I2 = 0 | Anti-EGFR plus chemotherapy probably improves OS compared with anti-VEGF plus chemotherapy for left-sided tumors |
| Difference: 96 fewer per 1,000 (95% CI, 144 fewer to 48 fewer) | |||||
| OS (right-sided tumors), 24 months | HR, 1.35 (95% CI, 1.0 to 1.8) (404 patients in three studies) | 575 deaths48 per 1,000 | 685 deaths per 1,000 | Moderatea; I2 = 0 | Anti-EGFR plus chemotherapy may have no effect or worsen OS compared with anti-VEGF plus chemotherapy for right-sided tumors |
| Difference: 110 more per 1,000 (95% CI, 0 fewer to 211 more) | |||||
| PFS (left-sided tumors), 24 months | HR, 0.86 (95% CI, 0.73 to 1.02) (689 patients in three studies) | 900 deaths or progressions per 1,000 | 814 deaths or progressions per 1,000 | Moderatea; I2 = 0 | Anti-EGFR plus chemotherapy may improve PFS compared with anti-VEGF plus chemotherapy for left-sided tumors |
| Difference: 86 fewer per 1,000 (95% CI, 38 fewer to 5 more) | |||||
| PFS (right-sided tumors), 24 months | HR, 1.53 (95% CI, 1.16 to 2.01) (689 patients in three studies) | 920 deaths or progressions per 1,000 | 979 deaths or progressions per 1,000 | Moderatea; I2 = 0 | Anti-EGFR plus chemotherapy may worsen PFS compared with anti-VEGF plus chemotherapy for right-sided tumors |
| Difference: 59 more per 1,000 (95% CI, 27 more to 74 more) | |||||
| Grade 3 or greater AEs | RR, 1.11 (95% CI, 1.02 to 1.20) (870 participants in two studies49,50) | 530 events48 per 1,000 | 588 events per 1,000 | Moderatea; I2 = 0% | Anti-EGFR plus chemotherapy may increase grade 3 or greater AEs compared with anti-VEGF plus chemotherapy |
| Difference: 58 more per 1,000 (95% CI, 11 more to 106 more) | |||||
Abbreviations: AE, adverse event; EGFR, epidermal growth factor receptor; FOLFIRI, folinic acid, fluorouracil, and irinotecan; FOLFOX, folinic acid, fluorouracil, and oxaliplatin; HR, hazard ratio; LS, left-sided primary tumor; OS, overall survival; PFS, progression-free survival; RR, relative risk; RS, rightsided primary tumor; VEGF, vascular endothelial growth factor.
Downgrade: inadequate/lack of blinding of participants and personnel; sidedness analyses were retrospective post hoc. Comparisons in included studies: FOLFOX plus panitumumab versus FOLFOX plus bevacizumab,49 FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab,50 and FOLFOX6 or FOLFIRI plus cetuximab versus FOLFOX6 or FOLFIRI plus bevacizumab.51