Real-world experience of pembrolizumab in microsatellite instability-high CRC: A Scottish multicenter analysis.
Authors: Aisha Ghaus, Ashley Pheely, Victoria Murdock, Hala Shareef, Leslie M. Samuel, Sally Clive, Fay Tough, Lisa Jane Rodgers
Journal: Journal of Clinical Oncology (2022)

54 Background: KEYNOTE-177 established pembrolizumab as a new standard of care in untreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Patients within clinical trials are not always representative of the general population. This underpins the importance of real-world data to offer insights into the outcomes achieved with anti-cancer therapies in routine practice. We report the initial efficacy and safety outcomes of patients treated with pembrolizumab for MSI-H CRC in Scotland. Methods: A retrospective analysis of all patients with advanced MSI-H CRC treated with pembrolizumab in the Scottish National Health Service was undertaken. Patient demographic and clinico-pathological data were collated via a standardised collection tool. Statistical analysis was performed using SPSS version 28. Results: 39 patients were identified (37 metastatic, 2 with locally advanced unresectable disease). All but 2 patients were treated in the first line setting. The median age was 68 years (range 48-82). 23 (59%) were age ≥65 years. 12 (30.7%) of patients were of Eastern Cooperative Oncology Group performance status (PS) 0, 23 (58.9%) of PS 1 and 4 (10.2%) of PS 2. 21 (53.8%) had BRAF V600E mutations. The median duration of pembrolizumab therapy was 24 weeks (range 2-104). After a median follow-up of 36 weeks (range 3-193), 5 deaths had occurred. The median progression free survival had not been reached. The overall response rate was 51% (20/39 patients), with 1 complete response observed. Radiological disease progression occurred in 7 patients (18%), 6 (86%) of which were BRAF V600E mutant. Treatment failure (radiologically confirmed disease progression or clinical suspicion of progression without radiological confirmation) occurred in 15 patients (38%). 3 out of 4 patients with PS 2 achieved a partial response. There were no grade ≥3 immune related adverse events. There was 1 treatment suspension due to grade 2 immune toxicity but no permanent discontinuations. Conclusions: Our real-world Scottish population was of poorer performance status than those recruited to KEYNOTE-177 (31% PS 0 vs. 49% in KEYNOTE-177). They were also older (59% age ≥65 years vs. 48% in the trial). Patients of PS 2 were excluded from the study, however 3 of our 4 PS 2 patients demonstrated a partial response to treatment, suggesting that PS 2 should not be an absolute contraindication to treatment. Our observed overall response rate was greater than that observed in KEYNOTE-177 (43.8%). Pembrolizumab was safe and well tolerated in this setting. These preliminary findings support the results of KEYNOTE-177. Long term survival data in our population is awaited. Further follow-up and patient numbers will allow for determination of possible clinico-pathological predictors (BRAF and KRAS status, Glasgow Prognostic Score, metastatic burden) of response to immunotherapy in this population.