Impact of age and gender on the efficacy and safety of panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC): Subgroup analysis of the PANAMA-study (AIO-KRK-0212).

3567 Background: Clinical trials in mCRC are usually conducted irrespective of gender and mostly also irrespective of age. However, gender- and age-associated differences relating to safety and efficacy in the treatment of mCRC are of presently moving into the focus of interest. We investigated the effect of gender and age on efficacy and safety in the PANAMA trial. Methods: PANAMA investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type metastatic colorectal cancer. In this post-hoc analysis, the study population was stratified for age (≤ 65 years versus > 65 years) and gender (male versus female). Evaluated efficacy endpoints were progression-free survival (PFS), overall survival (OS) of maintenance therapy and objective response rate (ORR) during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). Results: In total, 165 male and 83 female patients were randomized and treated. Male patients had a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS (HR 0.63; 95% CI 0.45-0.88; p = 0.006) and demonstrated a strong trend towards better ORR during maintenance therapy (Odds ratio 1.92; 95%CI 1.02-3.70, p = 0.053). In female patients, no difference regarding PFS was seen between treatment arms (HR 0.85; 95% CI 0.53-1.35, p = 0.491), while a trend towards better ORR with Pmab (Odds ratio 2.50; 95% CI 0.99-6.25; p = 0.063) was observed. Gender had no significant impact on OS, nor did age categories affect survival endpoints. Adverse events grade ≥ 3 occurring during maintenance therapy were comparable between male and female patients (12.9% vs 13.5%; p = 0.791) and in different age categories (p = 0.393). Conclusions: In the Panama trial, addition of Pmab to maintenance treatment with FU/FA improved outcome in RAS wild-type mCRC. This effect is irrespective of age and is pronounced in male patients. Our results support the relevance of gender in mCRC. Clinical trial information: NCT01991873. [Table: see text]