Osimertinib has emerged as a formidable contender, particularly as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutation-positive (EGFRm) status. A recently conducted real-world observational study has delivered insights into the long-term survival and treatment patterns of patients initiated on first-line osimertinib for advanced EGFRm NSCLC. The research was presented at the ESMO 2023 Congress (Abstract 1344P) held in Madrid, Spain.
Osimertinib, a third-generation, irreversible EGFR tyrosine kinase inhibitor (TKI), selectively targets EGFR mutations and has displayed potent activity against both EGFR-TKI sensitizing and EGFR T790M resistance mutations, positioning it as the preferred first-line choice for this patient population.
This real-world study tapped into the Flatiron Health database, identifying adults with Stage IIIB-IV EGFRm NSCLC who commenced first-line osimertinib monotherapy between April 2018 and March 2020. The study primarily focused on evaluating overall survival, time to next treatment or death (TTNTD), and treatment patterns, while also delving into secondary endpoints such as baseline characteristics and time to treatment discontinuation (TTD), serving as a surrogate for real-world progression-free survival (PFS).
Among the 773 patients enrolled in this real-world analysis, the median age was 70 years, with a significant representation of females (68%) and White patients (59%). Of the cohort, 54 percent had no known smoking history. The majority of patients displayed good performance status (ECOG PS 0 or 1), and a high percentage (89%) possessed Exon 19 deletion or L858R EGFR mutations.
As the real-world data matured, with a median follow-up of 24 months, the results showed the following outcomes: for all patients in the analysis, the median OS stood at 29.8 months with a median TTNTD of 18.5 months and a median TTD of 16.3 months. Equally impressive, a subset of patients closely mirroring the FLAURA trial (NCT02296125) inclusion criteria exhibited even better outcomes, with a median OS of 33.3 months, a median TTNTD of 22.3 months, and a median TTD of 19.4 months. Overall, 39 percent of patients received subsequent therapy with various treatment regimens being explored, including immunotherapy, chemotherapy, and EGFR-TKIs, indicating the dynamic nature of treatment patterns in the real world.
For additional insights into the study, Oncology Times connected with study author, Jorge Nieva, MD, a medical oncologist at the Keck School of Medicine of University of Southern California who specializes in lung cancer and head and neck cancer.
Oncology Times: Were there any specific factors or patient characteristics associated with a higher likelihood of receiving subsequent therapy? How did these subsequent treatments impact patient outcomes in terms of OS and TTNTD?
Nieva: "We did not find an association between the selection of next-line therapy and outcomes. However, we found that, in the real world, a minority of patients go on to get the next line of therapy and thus the numbers are small for the different regimens. Progression of disease and death was more common in patients with poor performance status, as well as those patients with central nervous system metastasis."
Oncology Times: What are the implications of these real-world findings for the clinical management of EGFR mutation-positive advanced NSCLC patients? How might these results influence treatment decisions and strategies in clinical practice?
Nieva: "In our population of patients, only a fraction went on to second-line therapy. This highlights the importance of using the very best first-line therapy available. Understanding the differences between the real-world and clinical trial results will help us to answer the big question right now in clinical practice-adding chemotherapy to osimertinib in the first line, as was reported recently at the IASLC 2023 World Conference on Lung Cancer in the FLAURA2 study.
"In FLAURA2, there was a PFS benefit to the addition of chemotherapy, but the overall survival data was not mature though there was no trend apparent. Our real-world data gives context to FLAURA2 as we find that in the real world only 39 percent of osimertinib-treated patients received second-line therapy, whereas in FLAURA2, 82 percent of these clinical trial patients received second-line treatment. This key difference between the real world and clinical trial populations is something we need to be mindful of as we interpret results of clinical trials and apply them to our patients in the real world."
Dibash Kumar Das is a contributing writer.