As Number of Targeted Therapies Increases, Challenges With Precision Medicine Are Not Going Away

There are an increasing number of targeted therapies in oncology, but challenges around biomarker testing and treatment selection remain.

For years, providers have made treatment recommendations based on the expected response of the average patient, but a one-size-fits-all approach to treatment does not work for some patients. Advances in precision medicine have led to more treatments tailored to the specific characteristics of an individual and the genetic profile of the tumor in oncology, said Amy Ware, director, specialty clinical solutions, Magellan Rx, during a session at Asembia’s Specialty Pharmacy Summit, held May 2-5 in Las Vegas.

There are an increasing number of targeted therapies coming out in oncology, Ware said, and there are challenges associated with these therapies. For instance, an abstract presented at the American Society of Clinical Oncology Annual Meeting 2019 found 69% of community oncologists either didn’t know the answer or incorrectly matched the molecular alteration to the targeted therapy.

“So, if these oncologists were presented with biomarker results, they wouldn't immediately know what therapy to prescribe for that biomarker,” she said.

Some genetic tests can analyze up to 80 genes, but the more genes being looked at the more variants of uncertain or unknown significance, Ware noted, which is a challenge for health plans. Often there are patients who are receiving too much testing while others are not receiving the recommended tests. For instance, Ware said, it’s known that patients with advanced ovarian cancer will benefit from BRCA testing.

“The health plan is better served making sure all patients receive recommended testing and limiting over testing in a small portion of the population,” she said.

Ware provided a short example list of drugs that currently need biomarker testing:

  • Encorafenib (Braftovi), which needs testing for BRAF V600E or V600K mutation
  • Trastuzumab deruxtecan (Enhertu), for HER2
  • Pralsetinib (Gavreto), for RET fusion
  • Cemiplimab-rwlc (Libtayo), for PD-L1
  • Entrectinib (Rozlytrek), for NTRK gene fusion and ROS1 arrangement(s)
  • Amivantamab-vmjw (Rybrevant) for EGFR exon 20 insertion mutations

And in non–small cell lung cancer (NSCLC) there are more than 10 mutations with targeted therapy options with a pipeline full of targeted therapies; however, fewer than 25% of patients with NSCLC receive testing for EGFR, ALK, ROS1, and BRAF mutations.

“After decades of chemotherapy and radiation being the lung cancer standard of care, researchers have made great progress identifying certain markers in lung cancer tumors and developing drugs to target those markers,” Ware said. But without patients going through biomarker testing, the oncologist and the care team cannot take advantage of these advancements in treatment.

Among patients with NSCLC, only 7% are getting tested for all 7 genes that were included in clinical guidelines, she noted.

Ware concluded by emphasizing the 2 biggest challenges: not all patients are getting biomarker testing that is recommended and providers can’t keep up with mutations and guidelines to prescribe the correct therapies. And with more targeted therapies in the pipeline, these problems are not going away, she said.

Right now, providers go through different laboratories to request biomarker testing, some of which are broad panels and others are nonspecific smaller panels. The broad panels may come with unnecessary costs for health plans, but the smaller panels could leave actionable biomarkers untested.

“In this scenario, patients can experience progressive disease and premature death due to suboptimal therapy selection,” Ware said. “In addition, health plans are paying for treatments that may have little to no clinical benefit to the patient.”