Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials
Phase meta-analysisN = 2,159
- Population
- Unresectable RAS wild-type metastatic colorectal cancer with known primary tumour side
- Design
- Retrospective pooled analysis of study-level hazard ratios and odds ratios from six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181) comparing chemotherapy plus an EGFR antibody (experimental arms) with chemotherapy or chemotherapy plus bevacizumab (control arms) in unresectable RAS wild-type metastatic colorectal cancer. Primary tumour location and RAS status were available for 2,159 of the 5,760 patients randomised across the six trials (37.5%): 515 right-sided and 1,644 left-sided. The authors caution that the predictive results were obtained retrospectively in subpopulations and that none of the studies contemplated a full treatment sequence strategy.
- Arms
- Control arms (control): Chemotherapy or chemotherapy plus bevacizumab (pooled control arms)
- Chemotherapy plus EGFR antibody (experimental): Chemotherapy plus an EGFR antibody (pooled experimental arms)
- People
- Arnold D
OSHR 0.75 (95% CI 0.67–0.84)OSHR 1.12 (95% CI 0.87–1.45)PFSHR 0.78 (95% CI 0.70–0.87)PFSHR 1.12 (95% CI 0.87–1.44)
Show the numbers
| Endpoint | Analysis | Chemotherapy plus EGFR antibody | Control arms | Effect |
|---|---|---|---|---|
| OSLeft-sided tumours (1,644 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 0.75 (95% CI 0.67–0.84)Pooled hazard ratio for death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P<0.001. |
| OSRight-sided tumours (515 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 1.12 (95% CI 0.87–1.45)Pooled hazard ratio for death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P<0.001. |
| PFSLeft-sided tumours (1,644 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 0.78 (95% CI 0.70–0.87)Pooled hazard ratio for progression or death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P=0.002. |
| PFSRight-sided tumours (515 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 1.12 (95% CI 0.87–1.44)Pooled hazard ratio for progression or death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P=0.002. |
| Endpoint | Analysis | Chemotherapy plus EGFR antibody | Control arms | Effect |
|---|---|---|---|---|
| OSLeft-sided tumours (1,644 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 0.75 (95% CI 0.67–0.84)Pooled hazard ratio for death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P<0.001. |
| OSRight-sided tumours (515 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 1.12 (95% CI 0.87–1.45)Pooled hazard ratio for death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P<0.001. |
| PFSLeft-sided tumours (1,644 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 0.78 (95% CI 0.70–0.87)Pooled hazard ratio for progression or death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P=0.002. |
| PFSRight-sided tumours (515 patients), retrospective pooled analysis | exploratoryArnold 2017 | — | — | HR 1.12 (95% CI 0.87–1.44)Pooled hazard ratio for progression or death, EGFR antibody plus chemotherapy versus control arms. Interaction between treatment effect and tumour side: P=0.002. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.75 | 0.67–0.84 |
| OS | 1.12 | 0.87–1.45 |
| PFS | 0.78 | 0.7–0.87 |
| PFS | 1.12 | 0.87–1.44 |
Appears in
Sources
Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017;28(8):1713-1729.