Addition of Panitumumab to Fluorouracil/Leucovorin as Maintenance Therapy for RAS Wild-Type Metastatic Colorectal Cancer

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In the German phase II PANAMA trial reported in the Journal of Clinical Oncology, Modest et al found that the addition of the monoclonal antibody panitumumab to fluorouracil (5-FU)/leucovorin maintenance therapy improved progression-free survival in patients with RAS wild-type metastatic colorectal cancer.

Study Details

In the open-label multicenter trial, 248 patients with stable disease or objective response after first-line induction with six cycles of 5-FU/leucovorin and oxaliplatin plus panitumumab were randomly assigned between May 2014 and February 2021 to receive maintenance panitumumab with 5-FU/leucovorin (n = 125) or 5-FU/leucovorin (n = 123). 5-FU/leucovorin and oxaliplatin plus panitumumab was given once every 2 weeks for six cycles, consisting of oxaliplatin at 85 mg/m2, leucovorin at 400 mg/m2, 5-FU at 2,400 mg/m2 (one dose administered over 48 hours), and panitumumab at 6 mg/kg body weight until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival.

Progression-Free Survival

At data cutoff, median follow-up was 36 months. Median progression-free survival was 8.8 months (80% confidence interval [CI] = 7.6–10.2 months) in the panitumumab group vs 5.7 months (80% CI = 5.6–6.0 months) in the control group (hazard ratio [HR] = 0.72, 80% CI = 0.60–0.85, P =.014).

Objective response rates during maintenance were 40.8% vs 26.0% (odds ratio = 1.96, 95% CI = 1.14–3.36, P = .02). Median overall survival was 28.7 months (95% CI = 25.4–39.1 months) in the panitumumab group vs 25.7 months (95% CI = 22.2–28.2 months) in the control group (HR = 0.84, 95% CI = 0.60–1.18, P = .32).


  • The addition of panitumumab to 5-FU/leucovorin in maintenance therapy significantly prolonged progression-free survival.
  • Median progression-free survival was 8.8 vs 5.7 months.

Adverse Events

Grade 3 or 4 adverse events during maintenance therapy occurred in 43.2% of the panitumumab group vs 26.0% of the control group. The most common in the panitumumab group were rash (7.2% vs 0% control group) and hypomagnesemia (6.4% vs 0%). Serious adverse events occurred in 12.8% vs 10.6% of patients.

The investigators concluded, “In RAS wild-type metastatic colorectal cancer, maintenance therapy with [5-FU/leucovorin] plus panitumumab induced a significantly superior progression-free survival compared with [5-FU/leucovorin] alone. If active maintenance therapy is aspired following induction therapy with [5-FU/leucovorin] and oxaliplatin plus panitumumab, [this regimen] appears to be the most favorable option.”

Dominik Paul Modest, MD, of the Department of Hematology, Oncology, and Tumorimmunology, Charité-Universitätsmedizin Berlin, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by AIO Studien gGmbH and Amgen Inc. For full disclosures of the study authors, visit

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