High Discordance in Recs From Tumor Board and Sequencing Vendors

Nancy A. Melville

November 03, 2022

Molecular tumor boards — teams of multidisciplinary experts that assess the molecular tumor profile of a patient's cancer — may frequently arrive at treatment recommendations that disagree with those generated by molecular testing vendors, a new study found.

The rate of discordance between recommendations from one institution's molecular tumor board and several next-generation sequencing vendors reached nearly 50%. The core reasons for the disagreements were low level of evidence, available alternatives, and tolerability concerns.

The researchers estimated that the molecular tumor board recommendations could potentially save more than $3.2 million in drug costs over a year.

The disagreement with the molecular tests "highlights the importance of clinical contextualization and multidisciplinary evaluation when developing a care plan tailored to each unique patient," first author Mary K. Walters, PharmD, a clinical pharmacist at Advocate Aurora Health in Downers Grove, Illinois, told Medscape Medical News. Furthermore, the drug cost avoidance "demonstrates the molecular tumor board’s potential financial benefit, which has not been well characterized before."

The study was published in October 2022 in JCO Precision Oncology.

The increasing array of molecular-based therapies, paired with molecular analytic methods such as next-generation sequencing, continue to advance precision medicine, helping identify patients who may or may not respond to specific therapies.

However, this practice is complicated by the range of genes being evaluated, the various algorithms used by next-generation sequencing vendors, as well as patient factors that may influence care.

To help manage this complexity, cancer centers have been increasingly establishing molecular tumor boards to ensure the best evidence-based recommendations are made in this genomics-driven setting.

Walters and colleagues wanted to better understand the level of agreement between recommendations made by their institution's molecular tumor board and several next-generation sequencing vendors. The research team conducted a retrospective analysis of recommendations made in 2021 for 962 patients with a variety of solid tumor and hematologic malignancies who received next-generation sequencing and whose case was reviewed by their institution's molecular tumor board.

Overall, discordance was high and varied across vendors. Vendors made treatment recommendations for 502 patients and the rate of discordance between the molecular tumor board and next-generation sequencing vendors was 45.6% (229 of 502).  

Discordance rates varied across three vendors — ranging from 8% to 30%. The most common reasons for disagreement between the tumor board and next-generation sequencing vendors were low level of evidence for the recommendation (88% of patients), an alternative standard of care available (60%), and tolerability concerns (42%).

The most common drug classes recommended by next-generation sequencing vendors but that clashed with tumor board recommendations included mTOR, PARP, MEK, and PIK3CA inhibitors in off-label settings.

The authors highlighted an example of this discordance using the PARP inhibitor olaparib. Olaparib received Food and Drug Administration approval for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. However, if an HRR target is identified in next-generation sequencing, a vendor may recommend that drug off label regardless of the indication.

"That lack of specific histologic and variant-level associations may be a limitation of the vendor's algorithms or machine learning in the space of a rapidly evolving knowledge base," the authors explained. This type of recommendation from vendors can also help explain why low level of evidence was "the most common discordance rationale in this review." 

Overall, the tumor board provided at least one therapy recommendation for 383 patients (39.8%), and 167 (17.4%) used a tumor board-recommended therapy.

Importantly, the tumor board’s alternative treatment strategy could avoid more than $21,000 in drug costs for 1 month or one cycle of a targeted therapy per discordant recommendation. Over the study period, the savings amounted to an estimated $3,209,070, the authors found.

This potential savings may reflect the high costs of newer drugs and underscore the need to carefully evaluate decisions to use them.

"Because of the very high cost of these new molecularly directed therapies, it is imperative that drugs are given to the right patient at the right time in the course of their disease to gain the maximal benefit for any given patient," said study coauthor Antony Ruggeri, MD, a hematology and oncology physician at Advocate Aurora Health in Milwaukee, Wisconsin.

Walters reported no disclosures. Ruggeri reported relationships with Elsevier and Astellas Scientific and Medical Affairs, Inc.

JCO Precision Oncology. Published October 2022. Abstract.

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