Marco Donia, Professor at University of Copenhagen (Københavns Universitet), shared a post on LinkedIn:
“How well do melanoma trial results predict routine-care outcomes? It depends on trial eligibility and on drug class.
We asked how much of the trial efficacy benchmark survives in routine first-line treatment, using Danish Metastatic Melanoma Database (DAMMED) (>95% national capture, 1909 patients) against pseudo-individual patient data (IPD) reconstructed from the registration trials.
Key Findings:
Immunotherapy in trial-eligible patients matches the benchmark.
- OS, PFS and MSS tracked the trials for anti-PD-1 monotherapy and ipi/nivo.
- Eligible patients did at least as well as the trial cohorts (e.g. median OS 47.6 vs 38.0 months for anti-PD-1).
The immunotherapy (IO) gap is concentrated in trial-ineligible patients.
- Anti-PD-1 OS HR 1.61 (95% CI 1.39-1.86); ipi/nivo 1.30 (1.02-1.66).
- 74.3% of first-line IO patients were trial-ineligible.
BRAF/MEK inhibitors underperform even in trial-eligible patients.
- OS HR 2.03 (1.60-2.56) in eligible, 2.73 (2.33-3.18) in ineligible; median real-world OS 9.2 vs 27.8 months in trials.
- 74.3% of first-line BRAF/MEKi patients were trial-ineligible.
Take-Home
- Real-world IO effectiveness reproduces regulatory efficacy but is conditioned on trial eligibility criteria
- The BRAF/MEKi picture is dominated by who still gets it first line, outcomes were much more poor in both trial-eligible and ineligible
n.b. These are benchmark-deviation HRs, not causal effects. Poor outcomes in ineligible patients largely reflect worse baseline prognosis (indication bias), not drug failure. The cohort was also ~10 years older than the trials.
Clinical Implication: expect real-world IO effectiveness to approximate benchmarks in eligible patients and to deviate in ineligible ones.
Beyond melanoma: the method is not melanoma-specific. The same approach quantifies the gap for any drug with a national registry, with implications for HTA and reimbursement, usable by agencies like Medicinrådet and NICE – National Institute for Health and Care Excellence.
Congratulations to the Danish Metastatic Melanoma Database (DAMMED) team and collaborating departments, and thanks to the patients who donated the use of their data.”
Title: Quantifying the efficacy-effectiveness gap in first line treatment of metastatic melanoma
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Authors: Yago Garitaonaindia, Adam Luczak, Christina Ruhlmann, Søren Kjær Petersen, Rasmus Blechingberg Friis, Troels Borch, Louise Guldbrandt, Inge Marie Svane, Henrik Schmidt, Lars Bastholt, Eva Ellebaek, Marco Donia
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You can also read:
Navigating Melanoma: The Cancer Research Institute’s Patient Guide to Immunotherapy
