Impact of Molecular Tumour Board Discussion on Targeted Therapy Allocation in Advanced Prostate Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2021 Dec 16

PMID 34912074

Citations 5

Authors

Peter H J Slootbeek

Iris S H Kloots

Minke Smits

Inge M van Oort

Winald R Gerritsen

Jack A Schalken

Marjolijn J L Ligtenberg

Katrien Grunberg

Leonie I Kroeze

Haiko J Bloemendal

Niven Mehra

Affiliations

Soon will be listed here.

Abstract

Background: Molecular tumour boards (MTB) optimally match oncological therapies to patients with genetic aberrations. Prostate cancer (PCa) is underrepresented in these MTB discussions. This study describes the impact of routine genetic profiling and MTB referral on the outcome of PCa patients in a tertiary referral centre.

Methods: All PCa patients that received next-generation sequencing results and/or were discussed at an MTB between Jan 1, 2017 and Jan 1, 2020 were included. Genetically matched therapies (GMT) in clinical trials or compassionate use were linked to actionable alterations. Response to these agents was retrospectively evaluated.

Results: Out of the 277 genetically profiled PCa patients, 215 (78%) were discussed in at least one MTB meeting. A GMT was recommended to 102 patients (47%), of which 63 patients (62%) initiated the GMT. The most recommended therapies were PARP inhibitors (n = 74), programmed death-(ligand) 1 inhibitors (n = 21) and tyrosine kinase inhibitors (n = 19). Once started, 41.3% had a PFS of ≥6 months, 43.5% a PSA decline ≥50% and 38.5% an objective radiographic response.

Conclusion: Recommendation for a GMT is achieved in almost half of the patients with advanced prostate cancer, with GMT initiation leading to durable responses in over 40% of patients. These data justify routine referral of selected PCa patients to MTB's.

Citing Articles

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[Molecular tumor boards in uro-oncology-prostate cancer].

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References

Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S . Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020; 383(24):2345-2357. DOI: 10.1056/NEJMoa2022485. View

Corn P, Heath E, Zurita A, Ramesh N, Xiao L, Sei E . Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. Lancet Oncol. 2019; 20(10):1432-1443. PMC: 6858999. DOI: 10.1016/S1470-2045(19)30408-5. View

Moore D, Kushnir M, Mak G, Winter H, Curiel T, Voskoboynik M . Prospective analysis of 895 patients on a UK Genomics Review Board. ESMO Open. 2019; 4(2):e000469. PMC: 6557082. DOI: 10.1136/esmoopen-2018-000469. View

Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G . Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020; 31(9):1119-1134. DOI: 10.1016/j.annonc.2020.06.011. View

Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N . A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol. 2018; 29(9):1895-1902. PMC: 6158764. DOI: 10.1093/annonc/mdy263. View

Chin L, Andersen J, Futreal P . Cancer genomics: from discovery science to personalized medicine. Nat Med. 2011; 17(3):297-303. DOI: 10.1038/nm.2323. View

Li M, Datto M, Duncavage E, Kulkarni S, Lindeman N, Roy S . Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2016; 19(1):4-23. PMC: 5707196. DOI: 10.1016/j.jmoldx.2016.10.002. View

Mateo J, Seed G, Bertan C, Rescigno P, Dolling D, Figueiredo I . Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest. 2019; 130(4):1743-1751. PMC: 7108902. DOI: 10.1172/JCI132031. View

Westgeest H, Uyl-de Groot C, van Moorselaar R, de Wit R, van den Bergh A, Coenen J . Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry. Eur Urol Focus. 2017; 4(5):694-701. DOI: 10.1016/j.euf.2016.09.008. View

10.

Dalton W, Forde P, Kang H, Connolly R, Stearns V, Gocke C . Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board. JCO Precis Oncol. 2018; 2017. PMC: 6039131. DOI: 10.1200/PO.16.00046. View

11.

Templeton A, Pezaro C, Omlin A, McNamara M, Leibowitz-Amit R, Vera-Badillo F . Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. 2014; 120(21):3346-52. DOI: 10.1002/cncr.28890. View

12.

Robinson D, Van Allen E, Wu Y, Schultz N, Lonigro R, Mosquera J . Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161(5):1215-1228. PMC: 4484602. DOI: 10.1016/j.cell.2015.05.001. View

13.

Postel-Vinay S, Boursin Y, Massard C, Hollebecque A, Ileana E, Chiron M . Seeking the driver in tumours with apparent normal molecular profile on comparative genomic hybridization and targeted gene panel sequencing: what is the added value of whole exome sequencing?. Ann Oncol. 2015; 27(2):344-52. DOI: 10.1093/annonc/mdv570. View

14.

Abida W, Cheng M, Armenia J, Middha S, Autio K, Vargas H . Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2018; 5(4):471-478. PMC: 6459218. DOI: 10.1001/jamaoncol.2018.5801. View

15.

Schwaederle M, Parker B, Schwab R, Fanta P, Boles S, Daniels G . Molecular tumor board: the University of California-San Diego Moores Cancer Center experience. Oncologist. 2014; 19(6):631-6. PMC: 4041669. DOI: 10.1634/theoncologist.2013-0405. View

16.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

17.

Pishvaian M, Blais E, Bender R, Rao S, Boca S, Chung V . A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients. JAMIA Open. 2020; 2(4):505-515. PMC: 6994017. DOI: 10.1093/jamiaopen/ooz045. View

18.

Le Tourneau C, Delord J, Goncalves A, Gavoille C, Dubot C, Isambert N . Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015; 16(13):1324-34. DOI: 10.1016/S1470-2045(15)00188-6. View

19.

Tredan O, Wang Q, Pissaloux D, Cassier P, de la Fouchardiere A, Fayette J . Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. Ann Oncol. 2019; 30(5):757-765. DOI: 10.1093/annonc/mdz080. View

20.

Koopman B, Groen H, Ligtenberg M, Grunberg K, Monkhorst K, de Langen A . Multicenter Comparison of Molecular Tumor Boards in The Netherlands: Definition, Composition, Methods, and Targeted Therapy Recommendations. Oncologist. 2020; 26(8):e1347-e1358. PMC: 8342588. DOI: 10.1002/onco.13580. View