RAS WT mCRC: Maintenance panitumumab + chemo improves PFS vs chemo alone

In patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who respond to first-line induction therapy with panitumumab plus fluorouracil, folinic acid and oxaliplatin (FOLFOX), maintenance panitumumab plus fluorouracil and folinic acid (FU/FA) significantly improves progression-free survival (PFS) vs FU/FA alone, results of the PANAMA trial have shown.

In the randomized, controlled, open-label phase II trial, 248 patients with stable disease, partial response or complete response following six cycles of first-line induction therapy with panitumumab plus FOLFOX were randomized 1:1 to receive maintenance therapy with panitumumab plus FU/FA (n=125; median age, 66 years; male, 69.6 percent; left-side primary tumour, 79.2 percent; liver metastasis, 79.2 percent; >1 metastatic organ, 43.2 percent) or FU/FA alone (n=123; median age, 65 years; male, 63.4 percent; left-sided primary tumour, 81.3 percent; liver metastasis, 84.6 percent>1 metastatic organ, 48.8 percent). [J Clin Oncol 2022;40:72-82]

After a median follow-up of 35.8 months in the panitumumab plus FU/FA arm and 36.3 months in the FU/FA alone arm, the primary outcome of PFS showed a significant 28 percent improvement with panitumumab plus FU/FA vs FU/FA alone (median, 8.8 months vs 5.7 months; hazard ratio [HR], 0.72; 80 percent confidence interval [CI], 0.60 to 0.85; p=0.014).

Overall survival (OS), with an event rate of 54.4 percent, numerically favoured the addition of panitumumab to FU/FA vs FU/FA alone (median, 28.7 months vs 25.7 months; HR, 0.84; 95 percent CI, 0.60 to 1.18; p=0.32).

Objective response rate was 40.8 percent in the panitumumab plus FU/FA group vs 26.0 percent in the FU/FA alone group (odds ratio, 1.96; 95 percent CI, 1.14 to 3.36; p=0.02). Objective responses to maintenance therapy were observed primarily (90.2 percent for panitumumab plus FU/FA vs 93.8 percent for FU/FA alone) in patients who had achieved objective responses following prior induction therapy.

Grade 3/4 adverse events (AEs) were reported in 43.2 percent vs 26.0 percent of patients  in the panitumumab plus FU/FA vs FU/FA alone group, while grade 3/4 serious AEs occurred in 12.8 percent vs 10.6 percent of the patients. The most common grade 3/4 AE was acneiform rash, which occurred in 7.2 percent of patients in the panitumumab plus FU/FA group vs none of the patients in the FU/FA alone group.

“In the context of antibody-based regimens for mCRC, there are three potential strategies of maintenance therapy, namely, monotherapy with a fluoropyrimidine, monotherapy with the monoclonal antibody used during induction therapy, or a combination of both,” explained the PANAMA investigators. “Interestingly, to the best of our knowledge, fluoropyrimidines as standard maintenance therapy of the pre-antibody era were not used as control arms in maintenance studies involving monoclonal antibodies.”

Results of the PANAMA trial – the first randomized trial to evaluate the addition of an anti-EGFR antibody to FU/FA maintenance therapy in patients with RAS WT mCRC – suggest that panitumumab plus FU/FA may be the most favourable option if active maintenance therapy is considered following induction therapy with panitumumab plus FOLFOX, the researchers concluded.

“However, without a standard of care [for maintenance therapy], the control arm of the PANAMA study could have been considered experimental, and vice versa,” they added. “Longer follow-up and future studies may help to understand to which extent maintenance therapy including anti-EGFR antibodies affects OS.”