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

V D de Jager; P Plomp; M S Paats; S van Helvert; A Ter Elst; A van den Berg; H J Dubbink; W H van Geffen; L Zhang; L E L Hendriks; T J N Hiltermann; B I Hiddinga; L B M Hijmering-Kappelle; M Jalving; J Kluiver; B Koopman; M van Kruchten; E M J van der Logt; B Piet; J van Putten; B H Reitsma; S R Rutgers; M de Vries; J A Stigt; M R Groves; W Timens; S M Willems; L C van Kempen; E Schuuring; A J van der Wekken

doi:10.1016/j.esmoop.2024.103966

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

ESMO Open. 2024 Nov;9(11):103966. doi: 10.1016/j.esmoop.2024.103966. Epub 2024 Nov 4.

Authors

V D de Jager¹, P Plomp², M S Paats³, S van Helvert⁴, A Ter Elst¹, A van den Berg¹, H J Dubbink⁵, W H van Geffen⁶, L Zhang⁷, L E L Hendriks⁸, T J N Hiltermann⁹, B I Hiddinga⁹, L B M Hijmering-Kappelle⁹, M Jalving¹⁰, J Kluiver¹, B Koopman¹, M van Kruchten¹⁰, E M J van der Logt¹¹, B Piet¹², J van Putten¹³, B H Reitsma¹⁴, S R Rutgers¹⁵, M de Vries¹⁶, J A Stigt², M R Groves⁷, W Timens¹, S M Willems¹, L C van Kempen¹, E Schuuring¹⁷, A J van der Wekken¹⁸

Affiliations

¹ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Department of Respiratory Medicine, Isala Hospital, Zwolle, the Netherlands.
³ Department of Pulmonary Medicine, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁴ Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁵ Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁶ Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
⁷ Structural Biology in Drug Design, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands.
⁸ Department of Pulmonary Diseases, GROW - School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
⁹ Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹⁰ Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹¹ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Molecular Diagnostics, Pathology Friesland, Leeuwarden, the Netherlands.
¹² Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
¹³ Department of Pulmonary Diseases, Martini Hospital, Groningen, the Netherlands.
¹⁴ Department of Pulmonology, Nij Smellinghe, Drachten, the Netherlands.
¹⁵ Department of Pulmonology, Treant Hospital Group, Scheper Hospital, Emmen, the Netherlands.
¹⁶ Department of Pulmonology, Tjongerschans, Heerenveen, the Netherlands.
¹⁷ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: e.schuuring@umcg.nl.
¹⁸ Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: a.j.van.der.wekken@umcg.nl.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: clinical decision making; molecular pathology; molecular tumor board; precision oncology; real-world data; targeted therapy.

MeSH terms

Academic Medical Centers
Adult
Aged
Aged, 80 and over
Female
Follow-Up Studies
Humans
Male
Middle Aged
Molecular Targeted Therapy* / methods
Mutation*
Neoplasms* / drug therapy
Neoplasms* / genetics
Retrospective Studies
Treatment Outcome