First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic

Suganija Lakkunarajah; Pauline T Truong; Jeffrey N Bone; Curtis Hughesman; Stephen Yip; Deepu Alex; Jason Hart; Philip Pollock; Sarah Egli; Melissa Clarkson; Mary Lesperance; Doran Ksienski

doi:10.21037/tlcr-23-81

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic

Transl Lung Cancer Res. 2023 Jul 31;12(7):1454-1465. doi: 10.21037/tlcr-23-81. Epub 2023 Jul 21.

Authors

Suganija Lakkunarajah¹, Pauline T Truong^{1

2}, Jeffrey N Bone³, Curtis Hughesman⁴, Stephen Yip⁴, Deepu Alex⁴, Jason Hart^{1

2}, Philip Pollock¹, Sarah Egli¹, Melissa Clarkson¹, Mary Lesperance⁵, Doran Ksienski^{1

2}

Affiliations

¹ BC Cancer-Victoria, British Columbia, Canada.
² University of British Columbia, Victoria, British Columbia, Canada.
³ Biostatistics, Clinical Research Support Unit, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
⁴ BC Cancer-Vancouver, British Columbia, Canada.
⁵ University of Victoria, Department of Mathematics and Statistics, Victoria, British Columbia, Canada.

Abstract

Background: The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively. Kaplan-Meier curves of OS and progression-free survival (PFS) from the start of osimertinib were plotted. The associations of baseline characteristics with PFS, and development of pneumonitis or dose reductions due to toxicity with OS were evaluated with hazard ratios estimated using univariable and multivariable Cox models.

Results: The cohort comprised 231 individuals. 58.7% of patients with de novo advanced NSCLC were initially diagnosed after presentation to the Emergency Room. At osimertinib initiation, 31.6% were aged ≥75 years and 45.5% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Median PFS and OS were 18.0 months [95% confidence interval (CI): 16.1-26.2] and 25.4 months (95% CI: 20.3-not reached), respectively. On multivariable analysis, age ≥75 years (vs. <75), ECOG PS 2/3 (vs. 0/1), ECOG PS 4 (vs. 0/1), current smokers (vs. never smokers), programmed death ligand 1 (PD-L1) expression ≥50% (vs. <1%), and L858R mutation (vs. exon 19 deletion) were associated with shorter PFS. Among 110 patients who progressed, 33.6% received subsequent therapy. A proportion of 16.5% of the cohort developed grade ≥3 adverse events. Pneumonitis from osimertinib (3.9% incidence) was weakly associated with shorter OS (hazard ratio: 2.59, 95% CI: 0.94-7.12, P=0.066); dose reductions were not associated with worse OS. 10.8% of patients developed COVID-19.

Conclusions: In a cohort receiving first-line osimertinib during the COVID-19 pandemic, ECOG PS ≥2 was observed in nearly half of patients at treatment initiation contributing to a median OS shorter than in FLAURA. The incidence of severe adverse events was low and dose reduction for drug toxicity did not impact OS. Identifying and reducing barriers to the diagnosis of NSCLC during the COVID-19 pandemic are required.

Keywords: COVID-19; Osimertinib; epidermal growth factor receptor (EGFR); lung cancer; survival.