Impact of molecular tumour board discussion on targeted therapy allocation in advanced prostate cancer

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.

Genetic Aspects and Molecular Testing in Prostate Cancer: A Report from a Dutch Multidisciplinary Consensus Meeting

“…When patient allocation into precision medicine trials is necessary, there was fair agreement (74%) that tumour genetic testing should ideally be performed in treatment-naïve mCRPC ( Supplementary material ). According to a recent study, 45.5% of Dutch patients harbour one or more actionable alterations in genes as per the ESMO Precision Medicine Working Group recommendation, with >60% of patients allocated within a precision medicine trial, including the Drug Rediscovery Protocol (DRUP) trial running in over 30 Dutch centres [33] . As targeted therapy and immunotherapy within this trial can be administered only after NHAs and taxanes, some panellists believed that many patients would not be suitable study candidates when tested in end-stage (mCRPC) disease.…”

Bridging the Divide – a Review on the Implementation of Personalized Cancer Medicine

“…Several studies have demonstrated the impact of MTB on the implementation processes for personalised cancer medicine [95]. MTBs were shown to improve the accuracy of genomic data interpretation and increased the proportion of patients who received targeted therapy [96][97][98]. This also includes improvement of the capacity to communicate with patients by facilitating the presentation of genomic information [99].…”

Bridging the Divide: A Review on the Implementation of Personalized Cancer Medicine

“…Several studies have demonstrated the impact of MTB on the implementation processes for personalized cancer medicine [ 123 ]. MTBs have been shown to improve the accuracy of genomic data interpretation and increase the proportion of patients who received targeted therapy [ 130 , 131 , 132 ]. This also includes the improvement of the capacity to communicate with patients by facilitating the presentation of genomic information [ 133 ].…”