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Trial availability, patient eligibility barriers to enrollment onto genomically matched trials
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Only a small percentage of patients with actionable gene alterations are eventually enrolled onto genotype-matched trials targeting these alterations, according to study results.
With the influx of targeted molecular therapies for the treatment of cancer, genomic profiling and matching patients to targeted therapies are imperative, according to study background.
“However, implementation of genomically informed therapy requires not only access to genomic profiling, but also the availability of molecularly targeted therapies matched to the genomic testing results,” Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics, at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Availability of clinical trials may not only differ from institution to institution, but may also differ between tumor types. Enrollment onto clinical trials is also limited by trial eligibility criteria, as well as availability of slots.”
Meric-Bernstam and colleagues conducted this prospective, single-institution study to evaluate the implementation of a Clinical Laboratory Improvement Amendments–compliant platform to conduct genomic sequencing after informed consent on patients with any malignancy. Physicians were able to enroll patients who they felt would best benefit from genomic testing and who were likely to consider enrolling onto a therapeutic clinical trial.
The current analysis included data from the first 2,000 consecutive patients (median age, 55 years) who underwent the protocol for genomic testing and who were enrolled into the study between 2012 and 2013. The most common malignancies in the cohort were breast (33%), colorectal (18%) and brain (13%) cancers.
Overall, 39% of the patients had at least one mutation in potentially actionable genes, the most common of which were TP53 (30.82%), PIK3CA (12.95%), KRAS (11.3%) and BRAF (7%). An additional 21% of patients had a somatic mutation that was presumed not actionable. However, only 11% of the patients with potentially actionable gene mutations went on genotype-matched trials that target those alterations, 7% of patients were treated on a genotype-selected trial that required a mutation for eligibility and 4% were treated on a genotype-relevant trial without biomarker selection.
Researchers further reviewed data from 429 patients with PIK3CA, AKT1, PTEN or BRAF mutations to gain insights on barriers to clinical trial enrollment. Two-hundred thirty of these patients returned to the institution for treatment, 116 of whom (50%) received a genotype-matched drug. Forty patients (17%) were treated on genotype-selected trials that required a mutation for eligibility, 16 (7%) were treated on a genotype-relevant trial that targeted genomic alterations without biomarker selection and 40 (17%) received a genotype-relevant drug off trial.
The researchers identified patient preference for non-investigational or localized treatment (n = 45), poor performance status (n = 4) or other reasons for trial ineligibility (n = 11), the lack of slots available on a trial (n = 4) or the lack of trials, and insurance denial (n = 1) as barriers to clinical trial enrollment.
During the study period, there was an increase in the number of genes for which there are genotype-selected trials. Although the researchers said they have used genomic testing to design genotype-specific, investigator-initiated trials and have recruited industry-sponsored and histology-independent basket trials, there is still a need for broader implementation.
“Novel trial approaches to explore antitumor efficacy in rare molecular subtypes and novel trial access mechanisms such as just-in-time trial access activating genomically matched trials appropriate for individual patient genotype are needed,” the researchers wrote.
Furthermore, Meric-Bernstam and colleagues noted that 31% of the patients did not have their genomic testing results acknowledged in their transcribed clinical notes and only 44% had documented discussion of the genotype-matched trials.
“It is unclear whether test results were indeed not appreciated and trial options not discussed or whether these were simply not documented,” the investigators wrote. “However, it is possible that alerting treating physicians that genomic testing results are available may improve trial accrual.”
As a result, MD Anderson has implemented a clinical trial alert system that will e-mail physicians alerts when actionable genome test results have been received along with a list of genotype-matched trials. MD Anderson has also created a Precision Oncology Decision Support Team to assist physicians who may feel uncertain about their knowledge of genomics.
“We expect that by increasing education and streamlining decision making, we can improve the implementation of genomically informed cancer therapy,” the researchers wrote. – by Anthony SanFilippo
Disclosure: Meric-Bernstam reports honoraria from, consultant/advisory roles with and research funding from AstraZeneca, Bayer, Calithera, Debiopharm, Genentech, Novartis, Roche, Sysmex and Taiho. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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