The median OS of patients who received FFT-based targeted therapy with TKIs was significantly higher than that of patients who received standard treatment — 38 months vs 26 months, respectively (P <.001). A significant difference in median PFS was also found among patients receiving targeted treatment (9 months) compared with those receiving nontargeted treatment (5 months, P <.001). The same was shown in an unadjusted Cox regression analysis, in which FFT-driven treatment choices were associated with significantly longer OS (hazard ratio [HR], 0.53; 95% CI, 0.43-0.65; P <.001) and PFS (HR, 0.54; 95% CI, 0.45-0.64; P <.001) than standard of care.3

Dr Djulbegovic told Cancer Therapy Advisor that there were 2 reasons why it was important to conduct this study. The first was providing a framework that could optimize treatment decisions, and the second was helping improve outcomes among patients with advanced lung cancer.

“Developments in genomics and related fields have grown exponentially,” he said. “Physicians find it difficult to analyze and interpret data that are increasingly available at the point of care.” As a result, he noted, decisions are more prone to error, with potentially devastating consequences for patients. “The more data you have, the larger the error/variance rates, which is what plagues ‘big data.’ Applying the FFT classifier does not produce error from variance, and hence, can be more accurate than ‘big data’ analyses.” Use of the FFT classifier is what he described as a “less is more” approach. He added, “Patients treated with the omics-based FFT decision tree lived longer than those with non–omic-based treatment, such as chemotherapy.”

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Among patients who received molecular testing, nearly three-quarters had a gene alteration that matched an available targeted therapy. EGFR was the most common alteration, reported in about half of the cohort; 90% of these patients received an appropriate targeted TKI treatment.3 Other detected biomarkers were ALK rearrangement and ROS1 fusion, of which 97% and 100% of patients, respectively, received appropriate targeted treatment. Those who received standard of care (chemotherapy or immunotherapy) were either not tested for biomarkers or had a KRAS alteration.3

Member of the NCCN Guidelines Panel for NSCLC, Debora Bruno, MD, MS, assistant professor of medicine at Case Western Reserve University in Cleveland, Ohio, told Cancer Therapy Advisor that the data from the current study differ from study results published 2 years ago. “These results contrast with those previously published by Presley et al,4 demonstrating a lack of survival benefit for broad-based genomic sequencing among advanced NSCLC in the community oncology setting.” But, she added, the study confirms the hypothesis that, when broad-based molecular testing results are well interpreted and receive prompt action, these data can enhance outcomes for patients with stage IV NSCLC and can help oncologists counsel patients on clinical trial availability — 2 reasons why the NCCN panel recommends molecular testing for patients with advanced lung cancer.

Another NCCN Guidelines Panel member, James Stevenson, MD, who is clinical assistant professor of medicine at Case Comprehensive Cancer Center, says the FFT management strategy, while of interest, is not necessarily new. “Rather, it clearly provides supporting evidence that the current NCCN Guidelines’ recommendations regarding biomarker-driven therapy selection for advanced NSCLC should be considered as standard of care.”

All said, Dr Djulbegovic and coauthors encourage larger, multicenter studies to corroborate their findings and help oncologists optimize omics-based treatment decisions and patient outcomes in advanced lung cancer.

References

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Non-Small Cell Lung Cancer. Version 6.2020 – June 15, 2020. Accessed August 21, 2020.
  2. Kalemkerian GP, Narula N, Kennedy EB, et al. Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice guideline update. J Clin Oncol. 2018;36(9):911-919. doi:10.1200/JCO.2017.76.7293[RH1] 
  3. Salgia R, Mambetsariev I, Pharaon R, et al. Evaluation of omics-based strategies for the management of advanced lung cancer. JCO Oncol Pract. Published online July 8, 2020[RH2] . doi:10.1200/OP.20.00117
  4. Presley CJ, Tang D, Soulos PR, et al. Association of broad-based genomic sequencing with survival among patients with advanced non-small cell lung cancer in the community oncology setting. JAMA. 2018;320(5):469-477. doi:10.1001/jama.2018.9824

Topics:

Lung Cancer Non-Small Cell Lung Cancer