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Multicenter Study
. 2025 Jan:199:108040.
doi: 10.1016/j.lungcan.2024.108040. Epub 2024 Nov 25.

The efficacy of continuing osimertinib with platinum pemetrexed chemotherapy upon progression in patients with metastatic non-small cell lung cancer harboring sensitizing EGFR mutations

Tejas Patil  1 , Dexiang Gao  2 , Alexander Watson  3 , Mandy Sakamoto  3 , Yunan Nie  4 , Amanda Gibson  5 , Michelle L Dean  5 , Benjamin A Yoder  3 , Eliza Miller  3 , Margaret Stalker  6 , Dara L Aisner  7 , Paul A Bunn  3 , Erin L Schenk  3 , Melina E Marmarelis  6 , Chiara Bennati  8 , Vishal Navani  5 , Yongchang Zhang  9 , D Ross Camidge  3
Affiliations
Multicenter Study

The efficacy of continuing osimertinib with platinum pemetrexed chemotherapy upon progression in patients with metastatic non-small cell lung cancer harboring sensitizing EGFR mutations

Tejas Patil et al. Lung Cancer. 2025 Jan.

Abstract

Introduction: For patients with EGFR mutant NSCLC who progress on osimertinib, the clinical benefit of continuing osimertinib with next line platinum pemetrexed chemotherapy remains unknown.

Methods: In this international, multi-center, retrospective cohort study, a total of 159 patients with EGFR mutant NSCLC who progressed on osimertinib and received platinum-pemetrexed therapy on progression from 2013 to 2023 were included. The data cutoff was December 31, 2023. Data analysis was conducted from January 2024 to June 2024. The primary endpoints were progression free survival (PFS) and overall survival (OS), analyzed using Kaplan-Meier methods. Multivariable Cox regression adjusting for patient-specific and cancer-specific factors was performed.

Results: 421 patients with EGFR mutant NSCLC with progression on osimertinib were identified, of which159 patients who met pre-specified inclusion criteria were divided into two groups: Cohort 1 (osimertinib + platinum-pemetrexed) included 50 patients (median [IQR] age, 59 [30 - 83] years; 36 [72.0 %] female; 11 [22.4 %] Asian) and Cohort 2 (platinum-pemetrexed alone) included 109 patients (median [IQR] age, 54 [25 - 80] years; 62 [56.9 %] female; 74 [64.9 %] Asian). Most patients were never smokers (Cohort 1, 37 [74.0 %]; Cohort 2, 66 [60.6 %]). One third of patients had baseline brain metastases (Cohort 1, 19 [38.0 %]; Cohort 2, 36 [38.3 %]). Both cohorts had a median of two prior lines of anti-cancer therapy. The addition of bevacizumab or immune checkpoint inhibitors (ICI) to next-line platinum-pemetrexed chemotherapy was more common in Cohort 2 (bevacizumab use, 30.3 % vs 8.0 %, p = 0.002; ICI use, 33.0 % vs 2.0 %, p = 0.001). With a median duration of follow up of 30 months, there was a significant PFS benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy (9.0 vs 4.5 months; HR 0.49, 95 % CI 0.32 - 0.74, p = 0.0032), also seen in subset analyses of patients who received first line osimertinib (n = 55, 11.0 vs 6.2 months; HR 0.41, 95 % CI 0.25 - 0.73, p = 0.002). Among patients with EGFR mutant NSCLC without brain metastases after progression on osimertinib, we found that continuing osimertinib with next line platinum pemetrexed significantly reduced the median time to CNS progression (n = 38; 7.0 vs 4.1 months; HR 0.47, 95 % CI 0.48 - 0.98, p = 0.01). After adjusted analysis, there was no significant OS difference between Cohorts 1 and 2 (19 months vs 13 months; HR 0.92, 95 % CI 0.60 - 1.39, p = 0.68).

Conclusions and relevance: For patients with EGFR mutant NSCLC who progress on osimertinib, there is a significant PFS, but not OS, benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy. The continuation of osimertinib with next line platinum pemetrexed chemotherapy appears to reduce the risk of CNS progression.

Keywords: Chemotherapy; EGFR; NSCLC; Osimertinib; Tyrosine kinase inhibitor.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
CONSORT diagram.
Fig. 2.
Fig. 2.
Progression free survival and overall survival. A. Kaplan-Meier curve of progression free survival of all patients in the dataset. B. Kaplan-Meier curve of overall survival of all patients in the dataset. C. Kaplan-Meier curve of progression free survival from a subset of patients who only received platinum pemetrexed chemotherapy (without concurrent bevacizumab or immune checkpoint inhibitors). D. Kaplan-Meier curve of overall survival from a subset of patients who only received platinum pemetrexed chemotherapy (without concurrent bevacizumab or immune checkpoint inhibitors).
Fig. 3.
Fig. 3.
Progression free survival and overall survival: subset analysis of patients with progression on first line osimertinib. A. Kaplan-Meier curve of progression free survival of a subset of patients treated with first line osimertinib. B. Kaplan-Meier curve of overall survival of a subset of patients treated with first line osimertinib.
Fig. 4.
Fig. 4.
CNS specific survival curves. A. Kaplan-Meier curve of progression free survival from a subset of patients without a history of brain metastases. B. Kaplan-Meier curve of progression free survival from a subset of patients with a history of brain metastases. C. Cumulative incidence of CNS progression among a subset of patients with serial brain imaging without brain metastases after progression on osimertinib. D. Cumulative incidence of CNS progression among a subset of patients with serial brain imaging with brain metastases after progression on osimertinib.
Fig. 5.
Fig. 5.
Forest plots. A. Forest plot of progression free survival. B. Forest plot of overall survival.
See this image and copyright information in PMC

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