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Ref Type Journal Article
PMID (39500140)
Authors de Jager VD, Plomp P, Paats MS, van Helvert S, Elst AT, van den Berg A, Dubbink HJ, van Geffen WH, Zhang L, Hendriks LEL, Hiltermann TJN, Hiddinga BI, Hijmering-Kappelle LBM, Jalving M, Kluiver J, Koopman B, van Kruchten M, van der Logt EMJ, Piet B, van Putten J, Reitsma BH, Rutgers SR, de Vries M, Stigt JA, Groves MR, Timens W, Willems SM, van Kempen LC, Schuuring E, van der Wekken AJ
Title Molecular Tumor Board of the University Medical Center Groningen (UMCG-MTB): outcome of patients with rare or complex mutational profiles receiving MTB-advised targeted therapy.
Journal Vol Issue Date Pages Journal Short Title
ESMO open 9 11 2024 Nov 04 103966 ESMO Open
URL
Abstract Text Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning. The objective of this study was to determine the effectiveness of MTB treatment recommendations for patients with rare and complex mutational profiles as implemented in the MTB of the University Medical Center Groningen (UMCG-MTB) in 2019-2020.A retrospective follow-up study was carried out to determine the clinical outcome of patients with uncommon or rare (combinations of) molecular aberrations for whom targeted therapy was recommended as the next line of treatment by the UMCG-MTB in 2019 and 2020.The UMCG-MTB recommended targeted therapy as the next line of treatment in 132 of 327 patients: 37 in clinical trials, 67 in the on-label setting, and 28 in the off-label setting. For on- and off-label treatment recommendations, congruence of recommended and received treatment was 85% in patients with available follow-up (67/79). Treatment with on-label therapy resulted in a response rate of 50% (21/42), a median progression-free survival (PFS) of 6.3 months [interquartile range (IQR) 2.9-14.9 months], and median overall survival (OS) of 15.8 months (IQR 6.4-34.2 months). Treatment with off-label therapy resulted in a response rate of 53% (8/15), a median PFS of 5.1 months (IQR 1.9-7.3 months), and a median OS of 17.7 months (IQR 5.1-23.7 months).Treatment with MTB-recommended next-line targeted therapy for patients with often heavily pretreated cancer with rare and complex mutational profiles resulted in positive overall responses in over half of patients. Off-label use of targeted therapies, for which there is sufficient rationale as determined by an MTB, is an effective treatment strategy. This study underlines the relevance of discussing patients with rare and complex mutational profiles in an MTB.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E IDH1 R132C melanoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with an overall survival of 51.1 months and a duration of treatment of 4.1 months in a melanoma patient harboring BRAF V600E and IDH1 R132C (PMID: 39500140). 39500140
EML4 - ALK ALK F1174V lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a complete response with a progression-free survival of 12.3 months, overall survival of 28.1 months, and a duration of treatment of 13.8 months in a patient with lung adenocarcinoma harboring EML4-ALK (e2:e20) with ALK F1174V (PMID: 39500140). 39500140
EML4 - ALK ALK V1180L lung adenocarcinoma predicted - sensitive Ceritinib Case Reports/Case Series Actionable In a retrospective analysis, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival of 7.3 months, overall survival of 26.3 months, and a duration of treatment of 8.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK V1180L (PMID: 39500140). 39500140
ALK fusion ALK G1202R lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 3.9 months, overall survival of 12.3 months, and a duration of treatment of 4.9 months in a patient with lung adenocarcinoma harboring an ALK fusion with ALK G1202R (PMID: 39500140). 39500140
EML4 - ALK ALK G1202R lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 21.2 months, overall survival of 34.0 months, and a duration of treatment of 24.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK G1202R (PMID: 39500140). 39500140
BRAF V600E IDH1 R132C lung squamous cell carcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with a progression-free survival of 14.8 months, an overall survival of 34.6 months, and a duration of treatment of 14.9 months in a patient with squamous non-small cell lung cancer harboring BRAF V600E and IDH1 R132C (PMID: 39500140). 39500140
ALK fusion ALK C1156Y lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a retrospective analysis, Alecensa (alectinib) treatment resulted in a partial response with a progression-free survival of 6.3 months, overall survival of 8.2 months, and a duration of treatment of 8.1 months in a patient with lung adenocarcinoma harboring an ALK fusion with ALK C1156Y (PMID: 39500140). 39500140
EML4 - ALK ALK F1174C lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a retrospective analysis, Alecensa (alectinib) treatment resulted in a partial response with a progression-free survival of 13.4 months, overall survival of 25.9 months, and a duration of treatment of 14.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C (PMID: 39500140). 39500140