TABLE 3.
Anti-EGFR Therapy Plus Doublet Chemotherapy Versus 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 | |
|---|---|---|---|---|---|
| Doublet Chemotherapy | Anti-EGFR Plus Doublet Chemotherapy | ||||
| OS (left-side), 24 months | HR, 0.69 (95% CI, 0.60 to 0.80) (916 patients in three studies) | 500 deaths43 per 1,000 | 380 deaths per 1,000 | Lowa,b; I2 = 0% | Anti-EGFR plus doublet chemotherapy probably improves OS compared with doublet chemotherapy for left-sided tumors |
| Difference: 87 fewer per 1,000 (95% CI, 160 fewer to 74 fewer) | |||||
| OS (right-side), 24 months | HR, 0.95 (95% CI, 0.72 to 1.26) (255 patients in three studies) | 600 deaths43 per 1,000 | 581 deaths per 1,000 | Lowa,b; I2 = 0% | Anti-EGFR plus doublet chemotherapy probably has little or no effect on PFS OS compared with doublet chemotherapy for right-sided tumors |
| Difference: 19 fewer per 1,000 (95% CI, 117 fewer to 85 more) | |||||
| PFS (left-side), 12 months | HR, 0.65 (95% CI, 0.54 to 0.79) (916 patients in three studies) | 620 deaths or progressions43 per 1,000 | 467 deaths or progressions per 1,000 | Lowa,b; I2 = 25.9% | Anti-EGFR plus doublet chemotherapy probably improves PFS compared with doublet chemotherapy for left-sided tumors |
| Difference: 153 fewer per 1,000 (95% CI, 213 fewer to 86 fewer) | |||||
| PFS (right-side), 12 months | HR, 0.77 (95% CI, 0.57 to 1.04) (255 patients in three studies) | 830 deaths or progressions43 per 1,000 | 744 deaths or progressions per 1,000 | Lowa,b; I2 = 0% | Anti-EGFR plus doublet chemotherapy probably has little or no effect on PFS compared with doublet chemotherapy for right-sided tumors |
| Difference: 86 fewer per 1,000 (95% CI, 194 fewer to 12 more) | |||||
| Grade 3–5 AEs44–47 | RR, 1.24 (95% CI, 1.18 to 1.3) (2,741 participants in four studies) | 601 per 1,000 | 745 per 1,000 | Moderate; I2 = 57% | Anti-EGFR plus doublet chemotherapy probably worsens grade 3–5 AEs, compared with doublet chemotherapy |
| Difference: 144 more per 1,000 (95% CI, 108 more to 180 more) | |||||
| Grade 3 skin toxicity47 | RR, 118.4 (95% CI, 16.59 to 844.7) (1,202 participants in one study) | 2 per 1,000 | 197 per 1,000 | High | Anti-EGFR plus doublet chemotherapy increases the risk of grade 3 skin toxicity, compared with doublet chemotherapy |
| Difference: 195 more per 1,000 (95% CI, 31 more to 1,687 more) | |||||
| Grade 3 acne-like rash47 | (1,202 participants in one study) | In the cetuximab group, 16% experienced grade 3 acne-like rash; no cases of acne-like rash were experienced in the control group | High | Anti-EGFR plus doublet chemotherapy increases the risk of acne-like rash, compared with doublet chemotherapy | |
Abbreviations: AE, adverse event; EGFR, epidermal growth factor receptor; HR, hazard ratio; LS, left-sided primary tumor; OS, overall survival; PFS, progression-free survival; RR, relative risk; RS, right-sided primary tumor.
a
Downgrade: open label trials; post hoc subgroup analyses.
b
Risk of bias assessment from Ciliberto et al.13