Panitumumab

In a phase III trial, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care.[83][Level of evidence B1]

In a phase III trial, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care.[83][Level of evidence B1]

Patients who received panitumumab experienced an improved PFS (8 weeks vs. 7.3 weeks; HR, 0.54; 95% CI, 0.44–0.66; P < .0001).

In a phase III trial, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care.[83][Level of evidence B1]

There was no difference in OS, which was thought to be the result of 76% of patients on best supportive care crossing over to panitumumab.

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1]

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1]

For patients with KRAS wild-type tumors, a statistically significant improvement in PFS was observed in those who received panitumumab/FOLFOX-4 compared with those who received only FOLFOX-4 (HR, 0.80; 95% CI, 0.66–0.97; stratified log-rank P = .02).

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1]

The median PFS was 9.6 months (95% CI, 9.2–11.1) for patients who received panitumumab/FOLFOX-4 and 8.0 months (95% CI, 7.5–9.3) for patients who received FOLFOX-4. OS was not significantly different between the groups (HR, 0.83; 95% CI, 0.67–1.02; P = .072).

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1]

For patients with KRAS-altered tumors, there was worse PFS with the addition of panitumumab (HR, 1.29; 95% CI, 1.04–1.62; stratified log-rank P = .02).

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1] › For patients with KRAS-altered tumors, there was worse PFS with the addition of panitumumab (HR, 1.29; 95% CI, 1.04–1.62; stratified log-rank P = .02).

The median PFS was 7.3 months (95% CI, 6.3–8.0) for panitumumab/FOLFOX-4 and 8.8 months (95% CI, 7.7–9.4) for FOLFOX-4 alone.

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1]

Subsequently, a retrospective analysis evaluated patients with wild-type KRAS exon 2 status for other KRAS and BRAF variants.[85][Level of evidence C1]

In the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study [NCT00364013], 1,183 patients were randomly assigned to FOLFOX-4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with KRAS-altered tumors separately.[84][Level of evidence B1] › Subsequently, a retrospective analysis evaluated patients with wild-type KRAS exon 2 status for other KRAS and BRAF variants.[85][Level of evidence C1]

Of the 620 patients who were initially identified as not having a variant in exon 2 of KRAS, 108 patients (17%) were found to have additional RAS variants and 53 patients (8%) were found to have BRAF variants. In a retrospective analysis, patients without any RAS or BRAF variants had a longer PFS (10.8 months vs. 9.2 months, P = .002) and OS (28.3 months vs. 20.9 months, P = .02) when assigned to the FOLFOX-4/panitumumab arm than the patients assigned to the FOLFOX-4 arm.

Similarly, the addition of panitumumab to a regimen of FOLFOX/bevacizumab resulted in a worse PFS and worse toxicity compared with a regimen of FOLFOX/bevacizumab alone in patients not selected for KRAS variant in metastatic colon cancer (11.4 months vs. 10.0 months, HR, 1.27; 95% CI, 1.06–1.52).[86][Level of evidence B1]

In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI/panitumumab.[87][Level of evidence B1]

In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI/panitumumab.[87][Level of evidence B1]

In a post hoc analysis, patients with KRAS wild-type tumors experienced a statistically significant PFS advantage (HR, 0.73; 95% CI, 0.59–0.90; stratified log-rank P = .004).

In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI/panitumumab.[87][Level of evidence B1] › In a post hoc analysis, patients with KRAS wild-type tumors experienced a statistically significant PFS advantage (HR, 0.73; 95% CI, 0.59–0.90; stratified log-rank P = .004).

The median PFS was 5.9 months (95% CI, 5.5–6.7) for panitumumab/FOLFIRI and 3.9 months (95% CI, 3.7–5.3) for FOLFIRI alone.

In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI/panitumumab.[87][Level of evidence B1]

OS was not significantly different. Patients with KRAS-altered tumors experienced no benefit from the addition of panitumumab.