First-line immune checkpoint inhibitors in elderly colorectal cancer patients in the real world: Retrospective phase of the multicenter ELDER CRC trial.

3539 Background: dMMR/MSI-H metastatic colorectal cancer (mCRC) is more common among the elderly. However, insufficient data about their treatment with immune checkpoint inhibitors (ICIs) are available from interventional and observational trials. Methods: ELDER CRC is an observational, multicenter Italian trial enrolling elderly (≥70 years [yrs]) patients (pts) treated with first-line ICI(s) for dMMR/MSI-H mCRC in the real world. Results from the retrospective cohort are presented. Results: 132 pts aged 77 yrs as median (IQR 74-82, range 70-93; <75: 32.6%; 75-79: 29.5%; ≥80: 37.9%) were enrolled across 10 Centers. They were mainly female (56.1%) in mediocre conditions (ECOG PS 1: 51.9%, ≥2: 22.2%; G8 ≤14: 80.5% [33/41 available]) with BRAF mutated (58.9% [73/124]), right primary tumor (80%), and synchronous metastases (54.5%) involving liver (34.8%) and/or peritoneum (37.9%). Almost all pts received monotherapy (pembrolizumab or nivolumab: 98.5%; nivolumab+ipilimumab: 1.5%) and most discontinued for PD (31.1%) or completion of 2 yrs (13.6%). 65.2% had an adverse event (AE), mainly fatigue (37.9%), skin rash (20.5%), hypothyroidism (17.4%), diarrhea (15.9%), and arthralgia (12.9%). Only 11% had G3-4 AE (G5=0), mainly gastrointestinal (3.8%), lung (3%), and fatigue (2.3%) and 10.6% discontinued ICI for AE. On 122 evaluable pts, ORR was 51.6% (38.5% PR + 13.1% CR) with 26.2% SD and 22.1% primary PD. At median follow-up of 25.9 months [mos] (22.3-30.3), mPFS was 32.2 mos (26.2-NE) with 56 events and mOS 45.8 mos (32.2-NE) with 46 events. 28.8% are still on treatment at the time of this analysis. Survival outcomes were not influenced by age groups. G8 >14 was related with better PFS (HR=0.79, p =0.06) and OS (HR=0.89, p =0.09). At multivariable model only neutrophils/lymphocytes ratio ≥3 was significantly associated with worse PFS (HR=1.91, p =0.03), while no variables with OS. Conclusions: Our results confirm the benefit of first-line immunotherapy for dMMR/MSI-H mCRC even among elderly pts treated in the real world, despite the substantial rate of right-sided and/or BRAF mut CRC pts and regardless of age group. The manageable safety profile of ICI(s) was also confirmed. G8 might be predictive of outcome but needs implementation in daily practice.