GenomOncology Further Refines Treatment Matching Capabilities with Integration of Prior Intervention Eligibility Criteria

One of the major advantages of using an automated software solution for clinical decision support is the rapid and accurate identification of treatment options for patients with genomic test results. GenomOncology's Precision Oncology Platform has a fully curated database of biomarker-driven or biomarker-relevant clinical trials that eligible patients can be matched against. This database contains ~ 10,000 trials, comprising all arm-level treatment eligibility curated with structured demographic, disease, and biomarker eligibility criteria that is updated on a nightly basis by the GenomOncology Content Team. Patient matching results from this database are used to power pathology reports to ordering oncologists, and in clinical decision support in oncology settings for our wide variety of clients using one or more GenomOncology products. 

Recently, we released a major update to the curated and matchable elements available within the GenomOncology Precision Oncology Platform with the introduction of prior treatment eligibility criteria. This information will aid in the process of honing in on the most clinically relevant treatment options for patients based on their treatment history, in addition to their disease and biomarker information.

CASE STUDY

Below details a case study that highlights a 57-year old female with recurrent Stage IV Pancreatic Adenocarcinoma to best illustrate the value of incorporating prior treatment eligibility criteria. This case study showcases the clinical trial results generated for the patient with, and without, the incorporation of their prior treatment history and overall clinical setting. 

To identify any potentially actionable genomic biomarkers to guide treatment selection, the patient’s ordering oncologist ordered the FoundationONE CDX Next Generation Sequencing assay. The test detected the following clinically relevant alterations:

  • Microsatellite Stable (MSS)

  • TMB-Low

  • KRAS G12R

  • RNF43 W321fs

  • TP53 P301fs

Variants of Uncertain Significance included mutations in BRD4, ERBB4, and HGF, along with a rearrangement in DOT1L. 

When analyzing the results available for this patient using GenomOncology's Precision Decision tool, 47 matched clinical trials were returned. Within the tool, each clinical trial is curated to match on each treatment arm on the basis of demographics, disease, and biomarker-based criteria. The database containing these trials is updated and maintained on a weekly basis. While these trial options are completely accurate for the patient based on the results of this genomic test, the introduction of prior treatment criteria matching generates a more clinically relevant set of results. 

When looking closely at the eligibility requirements over the set of 47 matched clinical trial results, 41 of the matched trials have some kind of prior treatment requirements, along with disease state (staging) and treatment state conditions. Types of prior treatment requirements can be inclusionary or exclusionary, and examples include:

  • The Patient must not have received a specific drug (i.e pembrolizumab) or drug regimen (i.e  fluoropyrimidine, oxaliplatin, and irinotecan-containing regimen).

  • The Patient must not have received a specific class of drug (i.e. WNT Inhibitor).

  • The Patient must have received any prior line of chemotherapy. 

These prior treatment requirements can also have distinct treatment and disease settings to consider, such as:

  • The Patient must have received at least 2 lines of systemic therapy.

  • Progression on 2 more lines of chemotherapy in the metastatic setting, including 5-fluorouracil, irinotecan, and oxaliplatin exposure.

Example of a Fully Curated Trial

Below is an example from the GenomOncology Curation Interface. As shown, the entirety of the curated elements of a single arm of a clinical trial are clearly visible. The patient would be eligible for the trial if they satisfy the biomarker + disease based requirements, and the drug in the treatment context section would be returned.

However, if prior treatment information is known for the patient, then those additional elements would be taken into consideration during the match process and matching would only consider demographics, disease, and biomarker criteria. 

Patient Prior Treatment History

This patient has had a relatively standard prior treatment history for pancreatic cancer patients, which includes:

  • Surgical resection.

  • Adjuvant chemoradiation.

  • Chemotherapy regimen (gemcitabine-cisplatin).

When the patient’s prior treatment history, as well as the advanced disease state and subsequent line treatment setting, are taken into account within GenomOncology’s Precision Decision tool, the matched clinical trial results are recalculated. This recalculation resulted in 31 matched trial options for the patient as compared to 47 previously when not considering prior treatment history. Below are some examples of how this matching is taking place.  

Trials Excluded Due to Prior Intervention Criteria

Due to the addition of the patient’s prior treatment history, a number of clinical trials were excluded from her treatment match results. For example, the patient originally matched to gemcitabine + nab paclitaxebased on their biomarker + disease criteria. However, due to the patient’s prior treatments, she was no longer eligible to receive that treatment. While this patient had previously received a regimen, including gemcitabine (gemcitabine-cisplatin), it was not the specific regimen required for the trial. Additional trials were also excluded as a result of the patient previously receiving chemotherapy and using anti-neoplastic agents.

Trials Included Due to Prior Intervention Criteria

A number of trials that matched based on the disease + biomarker basis are retained after incorporating prior intervention matching. For example, NCT03919292 states that the patient must not have received neratinib to be eligible for the KRAS mutation + Malignant Solid Tumor positive arm. This patient has not received neratinib before, and therefore is eligible. However, the overall trial eligibility also states that the patient must have both advanced disease and have progressed on standard therapies. In this case, all 3 criteria are captured by the GenomOncology Content team, and all 3 criteria are satisfied by the interpretation of the patient’s treatment history and treatment matching process. 

When looking at other possible dimensions of treatment matching, there are times when the prior treatment criteria includes generic drug or drug type statements. An example of this can be found in, NCT02079740, which says that the patient must have received at least one line of chemotherapy and experienced progression. This patient has previously received a regimen of gemcitabine-cisplatin, and in the GenomOncology drugs database (containing ~ 6,000 entries), drugs have ontological relationships so that it is known what ancestor and descendant drugs are related to individual drugs. By using this ontology, the algorithm knows that the drugs in this regimen are both types of chemotherapy, and therefore the eligibility requirement can be satisfied. This ability to bridge the distinctly received drugs for a patient to their higher level concepts offers a highly dynamic element to the matching capabilities.  

Learn More

Using the process of taking into account all clinically relevant information for patients along with their biomarker results leads to unprecedented relevancy in clinical decision support. Interested in learning more? Read more about how we integrate prior interventions eligibility criteria into our solutions.