Biomarker Testing in Advanced Cancer Still Lags Behind Guideline Recommendations

Only a third of patients with advanced cancer had molecular testing to help guide the use of targeted therapies, a review of 26,000 patients showed.

Overall, 35% of patients’ records had evidence of comprehensive genomic profiling (CGP). The rate increased modestly from 32% at the beginning of the study period to 39% at the end, reported Stacey DaCosta Byfield, PhD, of Optum in Eden Prairie, Minnesota, and co-authors in JAMA Network Open.

Among tested patients, those with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) were more likely to receive targeted therapy.

A “suboptimal percentage” of tested patients received targeted agents, although many patients received immune checkpoint inhibitors, suggesting CGP might have been used to identify patients with high tumor mutational burden, the researchers said.

“Given the well-established survival advantage for patients treated with biomarker-matched targeted therapies, this finding represents potential suboptimal care of patients with metastatic cancer, especially in cancer types in which targeted therapy is most appropriate,” they stated.

The cost of care was higher among patients who had biomarker testing versus those who did not, but did not differ significantly between CGP and non-CGP biomarker testing groups. Given that fact, together with the potential benefits of CGP, “the increased adoption of CGP that includes assessment of all guideline-recommended biomarkers may offer opportunities for improved outcomes,” DaCosta Byfield and colleagues concluded.

However, the findings should be interpreted within the context of an evolving landscape of precision oncology, Kenneth Kehl, MD, of Dana-Farber Cancer Institute in Boston, wrote in an accompanying commentary.

“The emergence of tumor-agnostic biomarker-selected therapies, such as immune checkpoint inhibitors for microsatellite instability-high tumors, ERBB2-targeted therapies across tumor types, and targeted therapies for rare fusions, increases the potential yield of broad biomarker testing,” he wrote. “The increasing availability of liquid biopsies … may further facilitate access to guideline-concordant and comprehensive biomarker testing. Liquid biopsies could broaden access to CGP and facilitate biomarker-driven treatment decisions, especially for patients in whom tissue biopsy specimens are challenging to obtain.”

Biomarker testing is necessary but not sufficient for delivery of effective precision oncology, Kehl continued.

“Testing can only improve patient outcomes if effective targeted therapies are available. Accelerating the development of such novel treatments will require that clinical trial eligibility criteria reflect populations of patients who may be eligible for a therapy and that trials be designed to facilitate patient access and minimize burden.” he wrote. “Robust drug development efforts to target novel biomarkers are essential to fully realize the potential of precision oncology and improve outcomes for all patients with cancer.”

Although clinical guidelines recommend biomarker testing to identify patients eligible for target therapy, available evidence suggests testing rates remain below recommendations. DaCosta Byfield and colleagues designed a study to assess the frequency of biomarker testing and the change in testing rates over time, and to compare use of targeted therapies and healthcare costs between tested and untested patients.

The analysis involved de-identified claims data from Optum Labs Data Warehouse. Eligible patients had advanced cancer diagnoses from January 2018 through January 2022, including breast, CRC, gastric, NSCLC, ovarian, and pancreatic. The primary outcomes were evidence of biomarker testing, receipt of targeted therapy during first-line treatment, and cost of therapy calculated per patient and per month.

The study population had a median age of 68, 70% of participants were enrolled in Medicare Advantage plans, and women accounted for 62% of the patients. The most common cancer was NSCLC (38%), whereas gastric cancer accounted for the fewest patients (3%).

Across tumor types, rates of biomarker testing ranged from a low of 17% with ovarian cancer to a high of 45% with NSCLC. For all tumor types, rates of testing increased before initiation of second-line therapy, ranging from 49% for breast and pancreatic cancer to 64% for gastric cancer. Rates of any biomarker testing, but particularly CGP, increased over the course of the study period. For example, CGP for patients with NSCLC increased from 12% in 2018 to 33% for January 2021 through January 2022. Testing rates were similar for patients with commercial insurance or Medicare Advantage.

Patients who had biomarker testing were more likely to receive targeted therapies: 12% for CGP, 6% for non-CGP testing, and 3% for no testing. Patients with NSCLC were more likely to receive targeted therapies after CGP (OR 3.41, 95% CI 2.87-4.05, P<0.001) or non-CGP testing (OR 2.16, 95% CI 1.80-2.60, P<0.001). Patients who had CGP testing were significantly more likely to receive first-line targeted therapy as compared with patients who had non-CGP biomarker testing (OR 1.57, 95% CI 1.31-1.90, P<0.001).

Similarly, patients with CRC and CGP were more likely to receive targeted therapies (OR 3.46, 95% CI 2.50-4.80, P<0.001) as were patients with non-CGP testing (OR 1.48, 95% CI 1.58-3.47, P<0.001). Patients with CGP were more likely to receive targeted therapies than were patients with non-CGP testing (OR 2.34, 95% CI 1.58-3.47, P<0.001). Because of small numbers, no other tumor-specific analyses were performed.

The authors acknowledged several limitations, including those inherent to a retrospective claims database, the potential for misclassification of different types of biomarker testing, and the inability to determine whether tested patients were evaluated for the full range of biomarkers recommended by guidelines.