Vectibix (Page 6 of 7)
14.2 First-line in Combination with FOLFOX Chemotherapy
Study 20050203(NCT00364013)
Study 20050203 was a multicenter, open-label trial that randomized (1:1) patients with mCRC who were previously untreated in the metastatic setting and who had received no prior oxaliplatin to receive Vectibix every 14 days in combination with FOLFOX or to FOLFOX alone every 14 days. Vectibix was administered at 6 mg/kg over 60 minutes prior to administration of chemotherapy. The FOLFOX regimen consisted of oxaliplatin 85 mg per m2 IV infusion over 120 minutes and leucovorin (dl-racemic) 200 mg per m2 intravenous infusion over 120 minutes at the same time on day 1 using a Y-line, followed on day 1 by 5-FU 400 mg per m2 intravenous bolus. The 5-FU bolus was followed by a continuous infusion of 5-FU 600 mg per m2 over 22 hours. On day 2, patients received leucovorin 200 mg per m2 followed by the bolus dose (400 mg per m2) and continuous infusion of 5-FU (600 mg per m2) over 22 hours. Study 20050203 excluded patients with known central nervous system metastases, clinically significant cardiac disease, interstitial lung disease, or active inflammatory bowel disease. The prespecified major efficacy measure was PFS in the subgroup of patients with wild-type KRAS mCRC as assessed by a blinded independent central review of imaging. Other key efficacy measures included OS and ORR.
In Study 20050203, in the wild-type K RAS subgroup (n = 656), 64% of patients were men, 92% White, 2% Black, and 4% Hispanic or Latino. Sixty-six percent of patients had colon cancer and 34% had rectal cancer. ECOG performance was 0 in 56% of patients, 1 in 38% of patients, and 2 in 6% of patients. Median age was 61.5 years.
The efficacy results in Study 20050203 in patients with wild-type K RAS mCRC are presented in Table 5 below.
Table 5 : Results in Patient s with Wild –type KRAS mCRC ( Study 20050203 )
| Primary Analysis | ||
| Wild-type KRAS population | Vectibix plus FOLFOX (n = 325) | FOLFOX Alone (n = 331) |
| PFS | ||
| Median (months) (95% CI) | 9.6 (9.2, 11.1) | 8.0 (7.5, 9.3) |
| Hazard ratio (95% CI)p-value | 0.80 (0.66, 0.97)p = 0.02 | |
| ORR | ||
| % (95% CI) | 54% (48%, 59%) | 47% (41%, 52%) |
E xploratory A nalysis of OS
An exploratory analysis of OS with updated information based on events in 82% of patients with wild-type K RAS mCRC estimated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone on OS (Figure 3). Median OS among 325 patients with wild-type K RAS mCRC who received Vectibix plus FOLFOX was 23.8 months (95% CI: 20.0, 27.7) vs 19.4 months (95% CI: 17.4, 22.6) among 331 patients who received FOLFOX alone (HR = 0.83, 95% CI: 0.70, 0.98).
Figure 3 : Kaplan –Meier Plot of Overall Survival in Patients with Wild –type KRAS mCRC ( Study 20050203 )
Retrospective e xploratory analys e s in the RAS wild –type sub group
Among the 656 patients with wild-type KRAS exon 2 mCRC, RAS mutation status was assessed for 620 patients using Sanger bidirectional sequencing and Surveyor® /WAVE® analysis. Of these 620 patients, approximately 17% of patients (n = 104) tumors harbored mutations in KRAS exons 3 or 4 or in NRAS exons 2, 3, and 4.
Retrospective subset analyses were then conducted among the subset of patients without RAS mutations (n = 512) as described above.
In the wild-type RAS subgroup, 65% of patients were men and 91% were White, 2% Black, and 5% Hispanic or Latino. Sixty-five percent of patients had colon cancer and 35% had rectal cancer. ECOG performance was 0 in 57% of patients, 1 in 37% of patients, and 2 in 6% of patients. Median age was 61 years.
Table 6: Results in Patients with Wild –Type RAS mCRC ( Study 20050203 )
| Primary Analysis | ||
| Wild-type RAS population | Vectibix plus FOLFOX (n = 259) | FOLFOX Alone (n = 253) |
| PFS | ||
| Median (months) (95% CI) | 10.1 (9.3, 12.0) | 7.9 (7.2, 9.3) |
| Hazard ratio (95% CI) | 0.72 (0.58, 0.90) | |
| OS* | ||
| Median (months) (95% CI) | 25.8 (21.7; 29.7) | 20.2 (17.5; 23.6) |
| Hazard ratio (95% CI) | 0.77 (0.64; 0.94) | |
| ORR | ||
| % (95% CI) | 58% (51%, 64%) | 45% (39%, 51%) |
*OS with updated information based on events in 82% of patients
Figure 4: Kaplan Meier Plot of Overall Survival in Patients with Wild –Type RAS–mCRC ( Study 20050203 )
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