1537O - Value of immune checkpoint blockade (ICB) in microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC)

Background

Adding ICB to cytotoxic chemotherapy is an emerging first-line treatment option for MSS/pMMR mCRC and/or selected subgroups. We aimed to quantify the value for money of alternating two cycles each of oxaliplatin-based chemotherapy (FLOX) and ICB (nivolumab), compared with standard-of-care FLOX alone, with and without biomarker-selected subgroups.

Methods

Individual participant data from METIMMOX-1, a phase II randomized controlled trial (n=76), were used to develop a partitioned survival model by parametrically fitting progression-free and overall survival. Health-related quality of life was determined via in-trial EQ-5D-5L surveys. Costs in 2023 Euros were estimated from a healthcare perspective and included drugs, tests, second-line and end-of-life care. We estimated the incremental cost-effectiveness ratio (ICER) for all randomized patients and for subgroups with the following cut-offs: ≥10% target lesion reduction at the first radiographic reassessment; C-reactive protein <5.0 mg/L when starting ICB; and tumor mutational burden (TMB) >8.0 mut/MB (the median value). Outcomes were discounted at 4% per year.

Results

Adding nivolumab for all patients provided 0.1175 quality-adjusted life years (QALYs) and incremental costs of >€75,000, yielding an ICER that is unlikely to be cost-effective. However, using biomarkers to select eligible patients doubled or tripled incremental QALYs while lowering incremental costs, leading to lower ICERs (Table). Table: 1537O

Selected results of the cost-effectiveness analysis by subgroup

Conclusions

Biomarker-guided selection for first-line ICB - compared to treating all unresectable MSS/pMMR mCRC patients - may improve incremental effectiveness while lowering incremental costs. The value of a TMB-based strategy is promising, and prospective validation is warranted.

Clinical trial identification

NCT03388190 (release date: 5 April, 2024).

Editorial acknowledgement

Legal entity responsible for the study

University Hospital Akershus, Lørenskog, Norway.

Funding

Bristol Myers Squibb.

Disclosure

S. Meltzer: Financial Interests, Personal, Advisory Board: GSK. A.H. Ree: Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda. All other authors have declared no conflicts of interest.