Best Management Practices for a Patient With Early-Stage Non-Small Cell Lung Cancer

Koosha Paydary, MD, Rush MD Anderson Cancer Center in Chicago, Illinois, discusses the course of treatment he would take for a patient with early-stage non-small cell lung cancer (NSCLC). 

Transcript:

Hello I'm Dr Koosha Paydary, I'm an assistant professor of medicine and a medical oncologist at Rush MD Anderson Cancer Center in Chicago, Illinois.

In the past few years, the treatment landscape of earlier stage non-small cell lung cancer that is EGFR-mutated has changed drastically. In 2020, we had [the] ADAURA trial that established the role of adjuvant osimertinib after resection of stage IB to III EGFR-mutated non-small cell lung cancer, as this trial showed a median progression-free survival of 65.8 months versus 28.1 months with a hazard ratio of .27, favoring osimertinib versus placebo in this patient population. Following that trial, the role of targeted therapies in resectable and unresectable non-small cell lung cancer has expanded. In 2024, we had the LAURA trial results announced and the LAURA trial was a phase 3 study that enrolled patients that had received concurrent chemotherapy and radiation and did not have disease progression. This patient population in fact was stage III unresectable EGFR-mutated non-small cell lung cancer and that trial also showed that osimertinib had a median progression-free survival benefit of 39.1 months versus 5.6 months with an impressive hazard ratio of .16. 

For this particular patient, choice C, which is upfront concurrent chemotherapy and radiation followed by osimertinib, is the correct answer. With respect to choice A, which is a neoadjuvant chemoimmunotherapy approach, it is important to remember that the evaluation of resectability should in fact be done prior to consideration of these strategies. In general, patients with bulky and invasive T4 disease with invasion into the critical nearby structures or those patients with multi-stage N2 disease that is bulky and invasive are likely best treated with non-surgical approaches, such as the concurrent chemotherapy and radiation which is the case for this particular patient. 

An important factor here is that [the] majority of the trials that in fact evaluated neoadjuvant chemoimmunotherapy approaches either did not include patients with EFR- and ALK-mutations, or only had [a] limited number of those patients. Now, we have emerging data such as the post hoc analysis of patients on the PACIFIC trial, which was consolidation durvalumab, that is showing that the benefit of durvalumab in this patient population with EGFR mutation[s] in fact is limited. This underscores the importance of NGS [next-generation sequencing] testing and molecular profiling for patients with earlier stage non-small cell lung cancer. With respect to choice E also, currently the neoADAURA trial is evaluating the role of neoadjuvant osimertinib with or without chemotherapy versus chemotherapy for stage II and III EGFR-mutated non-small cell lung cancer, but currently we do not have the results and until the results of that trial are announced, the role of neoadjuvant osimertinib in this patient population is unknown.