Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial SUNLIGHT demonstrated a statistically significant increase in overall survival (OS) and progression-free survival (PFS) for trifluridine-tipiracil plus bevacizumab compared to trifluridine-tipiracil alone, with hazard ratios of 0.61 and 0.44 respectively. This indicates a clear clinical advantage over the standard of care.
Cost effectiveness
The cost-effectiveness estimates for trifluridine-tipiracil plus bevacizumab were within the acceptable range for Healthcare resources, with ICERs below £30,000 per QALY gained. This suggests a strong economic value for the treatment.
Quality of life
The trial results indicated improvements in health-related quality of life, although the evidence was primarily derived from subgroup analyses and not all domains were significantly improved. The committee noted the treatment was well tolerated, suggesting a moderate positive impact on HRQoL.
Supporting Domains
Safety and Adverse Effects
The safety profile of trifluridine-tipiracil plus bevacizumab was reported as very good, with low rates of serious adverse events compared to existing treatments. The committee concluded that the treatment is well tolerated.
Comparator Selection
The treatment was compared against appropriate alternatives, including trifluridine-tipiracil alone and regorafenib, which are relevant in the context of current clinical practice for metastatic colorectal cancer.
Patient Population and Subgroups
The trial population was broadly representative of the intended patient population, with comprehensive subgroup analyses conducted. The committee noted that the results were likely generalizable to the Healthcare population.
Care Pathway Integration
The integration of trifluridine-tipiracil plus bevacizumab into existing care pathways is manageable, requiring only minor adjustments. The committee noted that it fits well within the current treatment landscape for metastatic colorectal cancer.
Resource Use and Cost Implications
The resource implications of adopting trifluridine-tipiracil plus bevacizumab are manageable, with the potential for cost savings due to improved patient outcomes and reduced need for subsequent treatments.
Evidence Quality and Robustness
The evidence base is robust, supported by a Phase 3 RCT (SUNLIGHT) and real-world data from the SACT dataset. The committee noted some uncertainties but considered the overall evidence to be credible.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding long-term outcomes and treatment effects, the committee found these manageable within the context of the unmet need for effective treatments in metastatic colorectal cancer.
