3539Background: 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.
First-line immune checkpoint inhibitors in elderly colorectal cancer patients in the real world: Retrospective phase of the multicenter ELDER CRC trial / Cassaniti M., Boccaccino A., Rossini D., Salvatore L., Puccini A., Valsecchi A.A., Ghirardini C., Zurlo I.V., Gelsomino F., Gallio C., Massaro G., Morelli C., Ferrari G., Di Francesco L., Airaghi C., Calegari M.A., Antonuzzo L., Tamberi S.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - ELETTRONICO. - 44:(2026), pp. 3539-3539. [10.1200/JCO.2026.44.16_suppl.3539]
First-line immune checkpoint inhibitors in elderly colorectal cancer patients in the real world: Retrospective phase of the multicenter ELDER CRC trial
Rossini D.;Antonuzzo L.;
2026
Abstract
3539Background: 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.
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