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Crizotinib for treating ROS1-positive advanced non-small-cell lung cancer

As of December 2024, MARA’s assessment finds Crizotinib’s reimbursement risk concentrated in clinical effectiveness, with cost effectiveness a strength; the current MARA Rating and full rationale are available in the report.

The assessment also weighs evidence quality and robustness: how solid the underlying evidence is on its own terms — trial design, size and endpoints — before any question of price is reached. The strength recorded in cost effectiveness carries weight because that domain asks whether the price asked stands in a defensible relationship to the benefit delivered — the core of most European reimbursement decisions.

Oncology

This rating sits within MARA’s Oncology coverage, alongside 153 other independently assessed treatments in the same area.

What payers will ask

Is the clinical benefit the kind payers reward? — Clinical effectiveness

The evidence for crizotinib indicates that it has comparable efficacy to entrectinib, which is the standard treatment for ROS1-positive advanced non-small-cell lung cancer. However, there is no direct trial data comparing crizotinib to entrectinib, and the evidence is primarily based on indirect comparisons. This limits the strength of the claim for superiority, thus justifying a B++ rating.

Does the economic case hold at the expected price? — Cost effectiveness

Crizotinib is suggested to have lower or similar costs compared to entrectinib, which supports its recommendation based on cost-effectiveness. The presence of a commercial arrangement further enhances its cost-effectiveness profile, justifying an A+ rating.

Is there quality-of-life evidence payers weigh? — Quality of life

The document does not provide any data or discussion regarding the impact of crizotinib on health-related quality of life, making it impossible to assess this factor.

Does the safety profile hold up for payers? — Safety and Adverse Effects

While the document does not detail specific adverse effects, crizotinib is generally considered to have an acceptable safety profile. The absence of significant safety concerns in the context of its use supports a rating of A.

Was the drug compared against what payers expect? — Comparator Selection

The comparator, entrectinib, is appropriate as it is the usual treatment for the same patient population. However, the lack of direct head-to-head trial data limits the robustness of the comparison, leading to a B++ rating.

Is the population defined the way payers need it? — Patient Population and Subgroups

The patient population for crizotinib is well-defined as adults with ROS1-positive advanced non-small-cell lung cancer. The guidance indicates that the treatment is recommended for those who have not previously received ROS1 inhibitors, which supports a moderate level of representativeness.

Does the drug fit how care is delivered and paid for? — Care Pathway Integration

Crizotinib can be integrated into existing treatment pathways with minimal disruption, as it is recommended alongside entrectinib, which is already in use. This suggests that only minor adjustments are needed for its implementation.

Are the wider system costs understood? — Resource Use and Cost Implications

The document indicates that crizotinib has a cost profile that is either lower or similar to that of entrectinib, suggesting a manageable budget impact. This supports a rating of A for resource use and cost implications.

Would the evidence survive payer scrutiny? — Evidence Quality and Robustness

The evidence base for crizotinib includes indirect comparisons but lacks direct Phase III trial data. This results in moderate concerns regarding the robustness of the evidence, justifying a B++ rating.

How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts

The guidance indicates that crizotinib addresses a significant unmet need in the treatment of ROS1-positive advanced non-small-cell lung cancer, which helps mitigate some uncertainties. However, the lack of direct comparative data introduces some residual uncertainty.

Be alerted when this rating changes:

Sample two-page MARA Rating report for the fictional drug Samplinib: the rating with its decision record, and the ten graded payer questions with the reasoning behind each
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