535P - Safety and efficacy of first-line immune checkpoint inhibitors in elderly colorectal cancer patients: An Italian real-world multicenter experience

Background

Due to their efficacy in dMMR/MSI metastatic colorectal cancer (mCRC) at the cost of limited adverse events (AEs), immune checkpoint inhibitors (ICIs) are often prescribed regardless of age. dMMR/MSI is more common among the elderly, which are underrepresented in clinical trials. Therefore, ICIs’ magnitude of benefit among elderly mCRC patients (pts) remains uncertain.

Methods

We retrospectively evaluated safety and efficacy of ICIs as first-line treatment of stage IV/unresectable stage III dMMR/MSI CRC pts aged ≥70 years (yrs), treated across 6 italian centers.

Results

On 67 total cases, pts were often female (N=37, 55%), with right-sided (N=50, 75%) and BRAF V600E mutated (N=38, 61%) CRC. Median age was 76 yrs (range 70-93, IQR 73-82), with 23 (34%) pts aged <75, 18 (27%) 75-79, 26 (39%) ≥80. Only 20 (30%) pts had a baseline geriatric evaluation, with G8 scoring ≤14 in 17 (85%), while 53/67 (79%) had ECOG PS ≤1. Primary tumor was resected in 47 (70%) pts. Out of 64 stage IV pts, 37 (58%) had synchronous metastases, with liver as only site in 11 (17%), >1 site in 20 (31%) and peritoneal involvement in 25 (39%). All pts were treated with pembrolizumab, except 1 receiving nivolumab/ipilimumab. Fourty-seven (70%) pts reported ≥1 AE, the most common being fatigue (45%), skin toxicities (19%), hypothyroidism (22%), arthralgia (18%), with grade (G) ≤2 in 37 (55%) pts and no G4-5 AEs. Treatment was temporarily, or definitively interrupted for AEs in 9 (13%), and 5 (7%) pts respectively. Among 60 pts with evaluable response, 28 (47%) achieved an ORR (CR: 6 [10%]; PR: 22 [37%]), 49 (82%) a DCR, with PD as best response in 11 (18%). With a median follow up of 13.5 months (mos), mPFS was 28.4 mos (23.5-NE) and mOS 34.1 (NE-NE). Among significant variables at univariate model, no-one retained its significancy at multivariate analysis for PFS, while liver-only metastasis (p=0.05), and age ≥80 yrs (p=0.04) remained significant for better OS.

Conclusions

First-line ICIs demonstrated safety and efficacy in elderly mCRC pts. Notably, the benefit was also shown in the oldest pts. These findings support the use of ICIs in elderly CRC pts, warranting further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.