Efficacy of Panitumumab in the Treatment of Refractory mCRC
A meta-analysis of 7 clinical trials showed that panitumumab therapy demonstrates a higher overall response rate compared to controls in patients with refractory metastatic colorectal cancer (mCRC).
Therapy of Refractory mCRC with Panitumumab
Panitumumab, a fully human monoclonal antibody against the human epidermal growth factor receptor (EGFR), has shown good efficacy against mCRC in patients without mutations in the KRAS gene. However, the results of studies in patients with refractory disease are inconclusive. The authors of this presented meta-analysis aimed to evaluate the efficacy of panitumumab in this specific patient population.
Methods of Analysis
The analysis included randomized controlled clinical trials published up to October 2018. Patients in all included studies had undergone prior chemotherapy, and the studies compared the efficacy of panitumumab with chemotherapy, targeted therapy, and a combination of chemotherapy and targeted therapy (with the exception of one study in which the control group received only the best supportive care).
Tab. Therapeutic Regimens in Clinical Trials Included in the Meta-analysis
Clinical Trial*) |
Study Arm |
Comparison Arm |
Shitara 2016 |
FOLFIRI + panitumumab |
FOLFIRI + bevacizumab |
Jerzak 2017 |
panitumumab |
irinotecan + cetuximab |
Hecht 2014 |
FOLFIRI + panitumumab |
FOLFIRI + bevacizumab |
Kim 2016 |
panitumumab + best supportive care |
best supportive care |
Hayashi 2018 |
panitumumab |
cetuximab |
Peeters 2015 |
FOLFIRI + panitumumab |
FOLFIRI |
Yamaguchi 2016 |
irinotecan + panitumumab |
irinotecan + cetuximab |
Note: *) References for individual studies are provided in the citation list within the source text. FOLFIRI – combined chemotherapy with leucovorin, 5-fluorouracil, and irinotecan.
Results
A total of 7 randomized studies with moderate to high evidence quality were included in the analysis. The aggregate results of 6 studies showed that progression-free survival (PFS) in the group treated with chemotherapy was comparable to the group treated with panitumumab (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.62−1.00; p = 0.05). All 7 studies were included in the overall survival (OS) analysis, and the results of both groups were again comparable (OR 1.01; 95% CI 0.81−1.27; p = 0.90).
However, the overall response rate (ORR) significantly differed between the two groups − patients treated with panitumumab achieved a significantly higher response rate compared to patients in the control groups (OR 3.71; 95% CI 1.34−10.31; p = 0.01).
Subgroup analysis showed that the efficacy of combined treatment with panitumumab was comparable to the efficacy of combination therapy based on cetuximab. It also found that adding panitumumab to irinotecan-based chemotherapy did not provide a significant benefit in terms of OS or PFS.
Conclusion
The presented meta-analysis suggests that while panitumumab therapy did not affect the survival of patients with refractory mCRC, the achieved response rate was higher. Further research should aim to accurately identify biomarkers that would enable the selection of patients who are most likely to benefit from this targeted therapeutic modality.
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Source: Duan K. F., Wang H. The efficacy of panitumumab in refractory metastatic colorectal cancer: a meta-analysis. J BUON 2019; 24 (4): 1457−1463.
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