Colon to Rectum
J Clin Oncol. 2022;40(1):72–82
Panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer: The randomized PANAMA trial (AIO KRK 0212)
Purpose: The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer.
Methods: Following first-line induction therapy with 6 cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival (OS), objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher’s exact test; odds ratios (ORs) were indicated when appropriate.
Results: Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cut-off, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 vs. 5.7 months; HR = 0.72; 80% confidence interval [CI]: 0.60–0.85; p = 0.014). OS (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 vs. 25.7 months; HR = 0.84; 95% CI: 0.60–1.18; p = 0.32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (OR = 1.96; 95% CI: 1.14–3.36; p = 0.02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%).
Conclusion: In RAS wild-type metastatic colorectal cancer, maintenance therapy with fluorouracil and folinic acid (FU/FA) plus panitumumab (Pmab) induced a significantly superior progression-free survival compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.