Panitumumab plus chemotherapy significantly improved survival in patients with metastatic colorectal cancer, compared with chemotherapy alone.
At ASCO GI this weekend, Amgen presented results from two pivotal phase III studies evaluating panitumumab (Vectibix) plus chemotherapy in patients with metastatic colorectal cancer (mCRC). Data from these randomized trials reinforce findings presented at the ECCO/ESMO congress last September that showed first- and second-line treatment with panitumumab (Vectibix) and chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. When stratifying outcomes according to status, the data also demonstrate the importance of this biomarker in predicting response to panitumumab.
The phase III PRIME ‘203’ multinational trial looked at the efficacy and safety of panitumumab plus chemotherapy in the first-line setting. A total of 1183 patients with treatment-naïve mCRC were randomized to receive 6.0 mg/kg of panitumumab plus FOLFOX4 every 2 weeks or FOLFOX4 alone. Although the study was designed prior to published reports about the ineffectiveness of EGFR inhibitors in patients with KRAS mutations, KRAS status was available for 93% of patients. Investigators reported that 60% (n = 656) had wild-type tumors and 40% (n = 440) had KRAS-mutated tumors.
In patients with wild-type tumors, the addition of panitumumab to chemotherapy significantly improved PFS by 1.6 months ( = .02). PFS in the panitumumab arm was 9.6 months compared with 8 months in the chemotherapy-only arm. Panitumumab was also associated with a 20% reduction in the risk of progression or death compared with chemotherapy alone (hazard ration [HR], 0.8). The panitumumab arm also had a higher rate of tumor response than the chemotherapy arm (55% vs 48%, respectively; = .07).
Overall survival (OS) was a secondary endpoint of the study, and though data showed a trend toward improved OS associated with panitumumab in patients with wild-type KRAS, the study did not meet its endpoint for OS. Median OS was 23.9 months for patients treated with panitumumab plus FOLFOX4 compared with 19.7 months for patients treated with chemotherapy alone. The 4.2-month difference in survival favoring the panitumumab arm did not reach statistical significance (HR, 0.83; = .072).
In patients with mutated KRAS, PFS was significantly inferior in the panitumumab arm compared with the chemotherapy-only group (8.8 mo vs 7.3 mo, respectively; = .02). This confirms other data that show the combination of an anti-EGFR antibody with an oxaliplatin-based chemotherapy regimen is ineffective in mCRC patients with KRAS mutations.
The PRIME ‘181’ trial investigated panitumumab plus conventional FOLFIRI chemotherapy as second-line treatment in 1186 patients with mCRC. This was also a randomized multinational study. As in the PRIME ‘203’ trial, 60% of patients in PRIME ‘181’ had wild-type KRAS.
In the patients with wild-type KRAS tumors, panitumumab as associated with a median PFS of 5.9 months versus 3.9 months for chemotherapy alone (HR, 0.73; = .004). The reduction in the risk of progression or death was 27% in the panitumumab arm. As in the first-line study, the trend toward OS favoring panitumumab did not reach statistical significance. Median OS was 14.5 months in the group that received panitumumab plus chemotherapy compared with 12.5 months for the group treated only with chemotherapy. Overall response, however, was significantly higher in the panitumumab arm compared with the chemotherapy arm (35% vs 10%; = .001).
As expected, panitumumab did not benefit patients with mutated KRAS tumors. This patient population had a median PFS of 5.0 months with combination therapy compared with 4.9 months for chemotherapy alone. OS was comparable in both arms.
In both trials, adverse effects were similar in all groups, with the exception of skin toxicity, a common adverse effect with EGFR inhibitors. Investigators described the combination of panitumumab with chemotherapy as well tolerated, with no unexpected toxicities.