Abstract 502P
Background
Phase 1 and 2 clinical trials of immune checkpoint inhibitors (CPI) show benefit for patients with mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). However, there is currently a lack of published, real-world data in this area. We examined outcomes of patients with dMMR mCRC treated with either nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI).
Methods
We conducted a retrospective analysis of 49 patients from 13 UK sites. All received NIVO (37/49) or NIVO+IPI (12/49) as part of the UK Bristol Myers Squibb Individual Patient Supply Request Programme, as per Article 5/1 of Directive 2001/83/EC. dMMR was confirmed by immunohistochemistry. The survival analysis cut-off date was 01/05/2020.
Results
All 49 patients had dMMR cancer: 46 mCRC, 1 appendiceal and 2 small bowel adenocarcinomas. Median age was 57 years (22–88); 55.1% were female; 59.2% had right-sided tumours and 33.3% had BRAFv600E mutant tumours. Median performance status was 1 (0-2). CPI was given to patients who had disease relapse within 6 months of adjuvant chemotherapy, or in the second to fourth-line setting. Response rates are summarised in the table. Median follow-up was 14.3 months (5.2–26.5). Overall median progression free survival (PFS) was 9.5 months (1.4–26.6). Median PFS was 8.4 months (1.4–26.6) and 13.5 months (5.3–25.6) in the NIVO and NIVO+IPI groups respectively. Median overall survival was not reached. There were 4 dose interruptions due to grade 3 CPI-related adverse events and 1 discontinuation due to grade 3 anaphylaxis, all observed on NIVO+IPI. There were no CPI-related deaths. Table: 502P
Tumour response outcomes by line of treatment.†
| Response | All patients (n=46) | Adjuvant relapse (n=9) | 2nd line CPI (n=18) | 3rd line CPI (n=10) | 4th line CPI (n=9) |
| Best overall response – no. (%) | |||||
| Complete response (CR) | 3 (6.5) | 2 (22.2) | 0 | 1 (10.0) | 0 |
| Partial response (PR) | 16 (34.8) | 3 (33.3) | 6 (33.3) | 4 (40.0) | 3 (33.3) |
| Stable disease (SD) | 17 (37.0) | 2 (22.2) | 8 (44.4) | 3 (30.0) | 4 (44.4) |
| Progressive disease (PD) | 10 (21.7) | 2 (22.2) | 4 (22.2) | 2 (20.0) | 2 (22.2) |
| Objective response rate (CR+PR) | 19 (41.3) | 5 (55.6) | 6 (33.3) | 5 (50.0) | 3 (33.3) |
| Disease control rate (CR+PR+SD) | 36 (78.3) | 7 (77.8) | 14 (77.8) | 8 (80.0) | 7 (77.8) |
†Three patients could not be evaluated due to cancer-related death prior to first CT scan.
Conclusions
This real-world data analysis demonstrates clinical benefit and acceptable toxicity consistent with prior trial results. This adds to the body of evidence supporting the use of NIVO and NIVO+IPI in patients with previously treated dMMR mCRC. Updated survival and clinico-pathological characteristics will be presented at ESMO 2020.
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.