Abstract
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.
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.
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.
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.
| Original language | English |
|---|---|
| Title of host publication | Annals of Oncology |
| Volume | 31 |
| Edition | Supplement 4 |
| DOIs | |
| Publication status | Published - 1 Sept 2020 |
