PARADIGM
Trial question
What is the role of panitumumab plus chemotherapy in patients with metastatic CRC?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
35.0% female
65.0% male
N = 733
733 patients (254 female, 479 male).
Inclusion criteria: patients with unresectable RAS wild-type metastatic CRC.
Key exclusion criteria: radiotherapy received within 4 weeks before enrollment; brain metastasis; body cavity fluid requiring treatment; synchronous cancers or metachronous cancers with a disease-free period ≤ 5 years.
Interventions
N=368 panitumumab plus mFOLFOX6 (panitumumab plus modified folinic acid, 5-FU, and oxaliplatin).
N=365 bevacizumab plus mFOLFOX6 (bevacizumab plus modified folinic acid, 5-FU, and oxaliplatin).
Primary outcome
Median overall survival in patients with negative hyperselection (lacking any gene alterations on plasma circulating tumor deoxyribonucleic acid)
40.7 months
34.4 months
40.7 months
30.5 months
20.4 months
10.2 months
0.0 months
Panitumumab plus
mFOLFOX6
Bevacizumab plus
mFOLFOX6
Significant
increase ▲
Significant increase in median overall survival in patients with negative hyperselection (lacking any gene alterations on plasma ctDNA) (40.7 months vs. 34.4 months; HR 1.32, 95% CI 1.09 to 1.61).
Secondary outcomes
No significant difference in median overall survival in patients with gene alteration (19.2 months vs. 22.2 months; HR 1.13, 95% CI 0.83 to 1.53).
Significant increase in median progression-free survival in patients with negative hyperselection (13.6 months vs. 12.8 months; HR 1.09, 95% CI 0.89 to 1.33).
Significant decrease in median progression-free survival in patients with gene alteration (7.8 months vs. 9.8 months; HR 0.6, 95% CI 0.44 to 0.81).
Safety outcomes
No significant difference in ≥ 3 grade adverse events.
Conclusion
In patients with unresectable RAS wild-type metastatic CRC, panitumumab plus mFOLFOX6 was superior to bevacizumab plus mFOLFOX6 with respect to median overall survival in patients with negative hyperselection (lacking any gene alterations on plasma ctDNA).
Reference
Kohei Shitara, Kei Muro, Jun Watanabe et al. Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. Nat Med. 2024 Mar;30(3):730-739.
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