Mortality on Osimertinib for Patients With EGFR-Mutant NSCLC

Joshua Sabari, MD, NYU Langone Health, discusses the efficacy of third-generation EGFR tyrosine kinase inhibitor (TKI) osimertinib among patients with EGFR-mutated advanced non-small cell lung cancer.

In a real-world attrition analysis, Dr Sabari and colleagues found the rate of patients who died before receiving a second line of therapy after receiving osimertinib in the first-line was similar to the mortality rate seen with prior first- and second-generation TKIs.

Transcript

Hi, I'm Dr. Joshua Sabari, thoracic medical oncology at NYU Langone Health Perlmutter Cancer Center in New York, NY, and I'll be discussing an abstract titled “Mortality Among EGFR Mutated Advanced Non-Small Cell Lung Cancer Patients After Starting First-line Osimertinib Treatment.” This is a real-world US attrition analysis.

We know that the first-line therapy for patients with EGFR mutation is generally osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI) and this was proven in the FLAURA trial, a randomized phase 3 study. However, all patients will unfortunately develop resistance, most commonly MET amplification as well as C797S. A retrospective real-world analysis of this patient population has shown that other patients with first- and second-generation EGFR TKIs, such as erlotinib, afatinib, gefitinib, unfortunately did not make it to the third-generation EGFR TKI.

We wanted to look at the analysis of mortality of US patients who did receive osimertinib in the first-line setting and where that takes us. The objective of this real-world analysis was an all-cause mortality of patients with EGFR mutations–activating mutations such as exon 19 and L858R–who received osimertinib monotherapy before receiving a second therapy in this setting.

We looked at data from many retrospective or real-world series including ConcertAI in Cambridge, Massachusetts, Patient360 Database as well as Flatiron Health, a large database housed in New York. We also looked at an advanced non-small cell lung cancer dataset as well.

We looked at this large cohort of patients who were diagnosed with advanced non-small cell lung cancer after January 1st, 2018. These are patients who were eligible at the time to receive osimertinib. Again, we looked at patients with exon 19 and 21-L858R mutations, and patients had to receive osimertinib in the first-line setting.

We looked at a couple of things. The proportion of patients who died after receiving first-line osimertinib monotherapy prior to starting a second therapy was calculated. We also looked at common demographics, clinical characteristics, and resistance to third-generation EGFR TKIs. We then stratified this by performance status and age.

When we look at patient mortality in the ConcertAI series and Patient360 database, among those who received first-line osimertinib, 518 patients died before receiving a second-line therapy. In the Flatiron database, 1,633 patients [total], about 23% or 329 patients died before receiving a second line of therapy. This is important. We want to use our best therapies upfront.

We then looked at demographics and disease characteristics similar across those who died before receiving a second-line therapy versus those who did not. This is no major predictor in my experience or my opinion in who would progress or who does not. When we looked at survival times stratified by age and ECOG performance status in the ConcertAI database, the median time to death was 277 days for patients with an ECOG performance status of 0 or 1 and 100 days for patients with ECOG of 2 or 3. Again, I want to explain the importance here of performance status. Those patients who have other comorbidities who may be leading them to have worsening performance status don't do as well with their treatment.

Also seen in the Flatiron data set, median time to death was 314 days in patients with performance status of 0 or 1.5, about 169 for those who had performance status of 2 and 3. When you look at survival times on first-line monotherapy, it is not age, but performance status that sticks out as being important.

We need further optimization of first-line therapy for patients with EGFR mutations that are activating exon 19-deletion and L858R to improve long-term outcomes, especially for our older patients and for those who have multiple comorbidities or, more importantly, poor performance status ECOG 2 or 3 because these patients, even with osimertinib – a third-generation EGFR TKI – are not doing that well.

Approximately one quarter of patients with EGFR mutations receiving first-line osimertinib died before receiving a second line of therapy. This was at a similar rate to what we've seen with prior first- and second-generation inhibitors. We saw no significant improvement with a third-generation EGFR TKI. Importantly, those who died before receiving a second line of therapy tended to be older, or they had a higher comorbidity score or poor performance status. More research is needed in this patient population.

Thank you for listening and appreciate your attention.

Source:

Girard N, Ohe Y, Kim T, et al. “Mortality among EGFR-mutated advanced NSCLC patients after frontline osimertinib treatment: A real-world, US attrition analysis” Presented at European Lung Cancer Congress 2023; March 29-April 1, 2023; Copenhagen, Denmark. Abstract P-19