Email this article Efficacy of immunotherapy (Prolgolimab) and targeted therapy (Trametinib and Dabrafenib, Cobimetinib and Vemurafenib) in adult patients with metastatic or unresectable skin melanoma: matching-adjusted indirect comparison
- Authors: Sapozhnikov K.V.1, Sokolova V.D.1, Sableva N.A.1, Tolkacheva D.G.1
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Affiliations:
- Russian Presidential Academy of National Economy and Public Administration
- Issue: Vol 24, No 4 (2022)
- Pages: 426-439
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/132975
- DOI: https://doi.org/10.26442/18151434.2022.4.202034
- ID: 132975
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Abstract
Aim. To assess the comparative clinical efficacy of Prolgolimab monotherapy versus combination therapy with BRAF/MEK inhibitors (Dabrafenib and Trametinib, Vemurafenib and Cobimetinb) in adult patients with metastatic or unresectable skin melanoma implementing a matching-adjusted indirect comparison (MAIC).
Materials and methods. We conducted a systematic search for randomized clinical trials of Prolgolimab, combinations of Dabrafenib and Trametinib, Cobimetinib and Vemurafenib. Unanchored MAIC was applied due to the absence of common comparator between trials. We determined effect modifiers based on an expert survey. The population from Prolgolimab studies was weighted using defined effect modifiers, followed by the approximation of survival curves.
Results. Systematic literature search revealed 4 RCTs that met the inclusion criteria: MIRACULUM, coBRIM, combi-v and combi-d. To increase the power of prolgolimab comparison, data from the observational study FORA were included in evidence synthesis and combined with data from MIRACULUM. We selected M staging and the proportion of patients with elevated LDH levels as effect modifiers. No significant differences (all p>0.05) were established between Prolgolimab and combination therapy with BRAF/MEK inhibitors for both OS after 1 year and PFS outcomes after 2 years from initiation.
Discussion. Despite the inclusion of observational data and the limitations of adjusted indirect comparison method, the results of this analyses are consistent with both other comparisons of anti-PD1 inhibitors with BRAF/MEK inhibitors, and with real world data. It is necessary to recompare targeted therapy and immunotherapy after five-year follow-up period due to peculiarities of time of onset of their effect with the presence of a primary “failure” with a gradual exit to a long “plateau” on anti-PD1 inhibitor’s therapy.
Conclusion. In these unanchored MAICs, Prolgolimab monotherapy showed comparable efficacy with combinations of BRAF/MEK inhibitors (Dabrafenib + Trametinib, Vemurafenib + Cobimetinib) in first line therapy of patients with metastatic or unresectable melanoma. This analysis may be relevant for clinical decision-making about the choice of the first line therapy for patients with BRAF mutation.
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##article.viewOnOriginalSite##About the authors
Kirill V. Sapozhnikov
Russian Presidential Academy of National Economy and Public Administration
Email: vdsokolova94@gmail.com
ORCID iD: 0000-0002-2476-7666
Cand. Sci. (Med.)
Russian Federation, MoscowValeriia D. Sokolova
Russian Presidential Academy of National Economy and Public Administration
Author for correspondence.
Email: vdsokolova94@gmail.com
ORCID iD: 0000-0001-7335-4852
Independent Expert
Russian Federation, MoscowNatalia A. Sableva
Russian Presidential Academy of National Economy and Public Administration
Email: vdsokolova94@gmail.com
ORCID iD: 0000-0002-5809-9221
Independent Expert
Russian Federation, MoscowDaria G. Tolkacheva
Russian Presidential Academy of National Economy and Public Administration
Email: vdsokolova94@gmail.com
ORCID iD: 0000-0002-6314-4218
Independent Expert
Russian Federation, MoscowReferences
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