The Case for Making Biomarker Testing the Standard

  • Advancements in understanding lung cancer’s molecular pathways have led to the development of targeted therapies, but biomarker testing remains underutilized.
  • Despite the effectiveness of therapies targeting specific mutations like EGFR, ALK, and ROS1, a significant gap exists in implementing biomarker testing as a standard of care.
  • Experts emphasize the importance of comprehensive genetic testing before treatment to improve patient outcomes, urging a shift in the medical community’s approach to lung cancer care.

Written by Dr. Kaique Filardi

Unlocking the secrets of cancer’s blueprint has revolutionized how we fight it. In lung cancer and beyond, our deepening knowledge of the molecular pathways that fuel malignancy has ignited a wave of innovative treatments. These breakthroughs, driven by the precise identification of oncogenic biomarkers, have transformed our approach to cancer therapy, offering targeted, life-changing interventions for patients.

Despite being a promising approach, the portion of patients with lung cancer receiving biomarker testing remains surprisingly low. Increasing awareness of these potentially life-saving genetic alterations is crucial to ensure that more patients receive the tailored treatments they need.

Dr. Mark Kris, a leading thoracic oncologist at Memorial Sloan Kettering Cancer Center, asserts that biomarker testing in lung cancer should be the standard of care for every patient before beginning treatment. 

“We have a test that says if the drugs will work or not, and we just can’t get over this hump of making it a standard of care for everybody. …You should use the best tests we have available, get the most precise information, and deliver the best treatment on day one,” Dr. Kris tells SurvivorNet. 

Targetable Biomarkers in Lung Cancer

The following panel depicts the most important biomarkers, or oncogenic drivers, for lung cancer.

  • EGFR mutations: Mutations in the epidermal growth factor receptor (EGFR) correspond to approximately 15 percent of non-small cell lung cancers (NSCLC). The presence of an EGFR mutation confers a more favorable prognosis. It strongly predicts sensitivity to EGFR tyrosine kinase inhibitors (TKIs), and therefore, targeted therapy should be used ahead of chemotherapy and immunotherapy.
  • ALK rearrangements: Rearrangements involving the anaplastic lymphoma kinase (ALK) tyrosine kinase are present in approximately 4 percent of NSCLCs.  It strongly predicts sensitivity to ALK TKIs (eg, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib), and treatment with these agents significantly prolongs progression-free survival (PFS).
  • ROS1 rearrangements: c-ROS oncogene 1 (ROS1) is a receptor tyrosine kinase that acts as a driver oncogene in 1 to 2 percent of NSCLC cases. The ROS1 tyrosine kinase is highly responsive to FDA-approved inhibitors such as crizotinib, entrectinib, and repotrectinib, which target ROS1/MET and ROS1/TRK in patients with ROS1 translocation.
  • RET rearrangements: The rearranged during transfection (RET) gene has been identified in 1 to 2 percent of adenocarcinomas. In this context, the RET inhibitor selpercatinib is the front-line setting rather than immunotherapy and/or chemotherapy.
  • NTRK fusions: Despite being rare (<1 percent prevalent), fusions involving the tropomyosin receptor kinases (TRK) offer tailored treatment with larotrectinib, entrectinib, and repotrectinib. 

“In those cancers [biomarker positive], the drugs we have that target the proteins that are activated by those mutations and infusions are extremely effective, shrink the cancer 80 or 90% of the time. …You really have to find those cancers, and you have to use these targeted therapies first,” Dr. Kris adds.

Bridging the Gap: Addressing the Underutilization of Biomarker Testing in Lung Cancer

Recent publications have shown the accuracy of screening for driver mutations. The resultant information helps choose between standard chemotherapy without targetable driver mutations versus upfront targeted therapies. 

For instance, a nationwide French study tested molecular profiling in lung cancer patients. Approximately 50 percent of tumors exhibited a genetic alteration, which led to the use of a targeted agent as first-line therapy in one-half of these cases. 

In this scenario, a genetic alteration was associated with improved first-line progression-free survival (10 versus 7.1 months) and overall survival (16.5 versus 11.8 months).

“The quicker you get that information into the patient’s hands, into the doctor’s hands, the better,” says Dr. Kris. 

In a similar vein, the Lung Cancer Mutation Consortium in the United States conducted a study where they analyzed tumors from 1,007 patients for at least one gene mutation. Of these, 733 patients underwent comprehensive testing for 10 different genes, leading to the identification of a targetable driver mutation in 64% of cases with full genotyping. 

Finally, Dr. Kris emphasizes that the medical community must shift its perspectives on lung cancer and fully leverage the advancements in diagnostic methods.

“We’ve got to get to that point where every physician that sees a person with lung cancer suspected … they get the material for the complete genetic testing. They’ve just got to do it,” he says.