Edgardo S. Santos, MD, FACP, clinical affiliate associate professor, Charles E. Schmidt College of Medicine, Florida Atlantic University, founding partner, Florida Precision Oncology, discusses the importance of identifying mechanisms of resistance in lung cancer.

When a patient progresses on first-line osimertinib (Tagrisso), it is important to molecularly restage the patient with a liquid biopsy to identify mechanisms of resistance, Santos explains. If the liquid biopsy is positive for an actionable alteration, the patient can proceed with targeted therapy, dual-targeted therapy, or a clinical trial, Santos says. If the liquid biopsy is negative, another option is to do a tissue biopsy if the patient has an accessible lesion, Santos adds.

Moreover, it is important to use a platform in which the next-generation sequencing investigates the RNA in addition to the DNA, Santos continues. This is important to do because evaluating the RNA and DNA makes it very difficult for protein escape, Santos concludes.

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Edgardo S. Santos, MD, FACP, discusses the importance of identifying mechanisms of resistance in lung cancer. 


Dr. Santos on Identifying Mechanisms of Resistance in Lung Cancer 

Edgardo S. Santos, MD, FACP, FCCP, a medical oncologist of internal medicine at Boca Raton Regional Hospital, discusses the FDA approval of the combination of ramucirumab (Cyramza) and erlotinib (Tarceva) for the frontline treatment of patients with metastatic non—small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 19 deletions or exon 21 substitution mutations.

The May 30, 2020 approval follows a 6 to 5 recommendation vote from the FDA's Oncologic Drugs Advisory Committee and is based on findings from the phase 3 RELAY trial. In the study, results showed that the addition of ramucirumab to erlotinib led to a 41% reduction in the risk of disease progression or death compared with erlotinib alone in the first-line treatment of patients with 

At a median follow-up of 20.7 months, the investigator-assessed median progression-free survival (PFS) with the ramucirumab regimen versus erlotinib alone was 19.4 months (95% CI, 15.4-21.6) versus 12.4 months (95% CI, 11.0-13.5), respectively (HR, 0.59; 95% CI, 0.46-0.76; 

 <.0001). The approval is not likely to impact the use of osimertinib, as the third-generation EGFR TKI is the preferred agent in this setting, says Santos. However, the combination could be an option for patients with exon 21 substitution mutations, concludes Santos.

Edgardo S. Santos, MD, FACP, FCCP, discusses the FDA approval of the combination of ramucirumab and erlotinib for the frontline treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor EGFR Ex19del or Ex21 substitution mutations.

Edgardo S. Santos Castillero, MD, FACP, FASCO

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Dr. Santos on Identifying Mechanisms of Resistance in Lung Cancer

Dr. Santos on the FDA Approval of Ramucirumab/Erlotinib in EGFR-Mutant NSCLC