The comparisons between arms A and B and arms A and C were analyzed and published separately.[64,65]
In patients with KRAS wild-type tumors (arm A, n = 367; arm B, n = 362), OS did not differ between treatment groups (median survival, 17.9 months [interquartile range (IQR) 10.3–29.2] in the control group vs. 17.0 months [IQR, 9.4–30.1] in the cetuximab group; HR, 1.04; 95% CI, 0.87–1.23, P = .67). Similarly, there was no effect on PFS (8.6 months [IQR, 5.0–12.5] in the control group vs. 8.6 months [IQR, 5.1–13.8] in the cetuximab group; HR, 0.96; 0.82–1.12, P = .60).[64,65][Level of evidence: 1iiA] The reasons for lack of benefit in adding cetuximab are unclear. Subset analyses suggest that the use of capecitabine was associated with an inferior outcome, and the use of second-line therapy was less in patients treated with cetuximab.
There was no difference between the continuously treated patients (arm A) and the intermittently treated patients (arm C). Median survival in the intent-to-treat population (n = 815 in both groups) was 15.8 months (IQR, 9.4–26.1) in arm A and 14.4 months (IQR, 8.0–24.7) in arm C (HR, 1.084; 80% CI, 1.008–1.165). In the per-protocol population, which included only those patients who were free from progression at 12 weeks and randomly assigned to continue treatment or go on a chemotherapy holiday (arm A, n = 467; arm C, n = 511), median survival was 19.6 months (IQR, 13.0–28.1) in arm A and 18.0 months (IQR, 12.1–29.3) in arm C (HR, 1.087, 95% CI, 0.986–1.198). The upper limits of CIs for HRs in both analyses were greater than the predeﬁned noninferiority boundary. While intermittent chemotherapy was not deemed noninferior, there appeared to be clinically insignificant differences in patient outcomes.
Approximately 15% to 25% of colorectal cancer patients will present with liver metastases at diagnosis, and another 25% to 50% will develop metachronous hepatic metastasis following resection of the primary tumor.[66,67,68] Although only a small proportion of patients with liver metastasis are candidates for surgical resection, advances in tumor ablation techniques and in both regional and systemic chemotherapy provide a number of treatment options.
Hepatic metastasis may be considered to be resectable based on the following:[17,21,24,25,26,27]
- Limited number of lesions.
- Intrahepatic locations of lesions.
- Lack of major vascular involvement.
- Absent or limited extrahepatic disease.
- Sufficient functional hepatic reserve.
For patients with hepatic metastasis considered to be resectable, a negative-margin resection has resulted in 5-year survival rates of 25% to 40% in mostly nonrandomized studies, such as the NCCTG-934653 trial.[17,21,24,25,26,27] Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection.