Clinical outcomes in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) in the pre-immunotherapy era.

Abstract

65 Background: Data on clinical treatment outcomes of systemic non-immunotherapy in patients with MSI-H mCRC are limited due to low incidence. Real world data can support the interpretation of immunotherapy studies. Our aim is to provide insight on clinical outcomes of patients with MSI-H mCRC treated with systemic non-immunotherapy. Methods: We describe an observational cohort study with real-world data from the Netherlands Cancer Registry during 2015-2018 (N=383) and trial-based data from three prospective phase III first-line clinical trials: CAIRO, CAIRO2 and CAIRO3 (N=54). We investigated progression free survival (PFS) and overall survival (OS), which were defined as time from the start of first-line (PFS1/OS1), second-line (PFS2/OS2) and third-line (PFS3/OS3) of systemic non-immunotherapy until disease progression or death, respectively. Furthermore, we investigated objective response rate (ORR), which was defined as the proportion of patients with a complete or partial response as best response after first-line (ORR1), second-line (ORR2) and third-line (ORR3). Results: A total of 437 patients with MSI-H mCRC were analyzed. The proportion of patients receiving at least one line of systemic non-immunotherapy was 63%, 21% received two lines, and 5% received three lines. Patients receiving one line of therapy (N=270) had a median age of 69, 50% were female, 49% had a WHO performance score of 0, 70% had a right-sided tumor, 72% had synchronous mCRC, and 64% of those with synchronous mCRC received primary tumor resection. When known, 52% of patients harbored a BRAF mutation and 21% a RAS mutation. The results of OS, PFS, and ORR are summarized. Conclusions: To our knowledge these results provide insight on clinical outcomes in the largest observational cohort of patients with MSI-H mCRC treated with systemic non-immunotherapy to date. We showed a median PFS1 of 5.9 months and an OS1 of 14.1 months, which are in distinct contrast with patients in MSI-H mCRC trials receiving mono-immunotherapy in which a median PFS1 of 16.5 months was reached and a median OS1 was not reached after median follow-up of 44.5 months. Only 21% of patients in our observational cohort reached second-line of systemic non-immunotherapy and 5% third-line. Our results underline the importance and early access to immunotherapy in the MSI-H mCRC population. [Table: see text]