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Review
. 2025 Aug 9;32(8):448.
doi: 10.3390/curroncol32080448.

Recent Advances in the Management of EGFR-Mutated Advanced Non-Small Cell Lung Cancer-A Narrative Review

Prabhat Gautam Roy  1 , Davida Reingold  2 , Neha Pathak  3 , Saurav Verma  4 , Aarushi Gupta  2 , Nicholas Meti  5 , Consolacion Molto  6 , Prabhat Singh Malik  1 , Geordie Linford  2 , Abhenil Mittal  2
Affiliations
Review

Recent Advances in the Management of EGFR-Mutated Advanced Non-Small Cell Lung Cancer-A Narrative Review

Prabhat Gautam Roy et al. Curr Oncol. .

Abstract

The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 demonstrating improvement in PFS with the addition of chemotherapy to Osimertinib and MARIPOSA, showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system; therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and the lack of data post-progression on novel first-line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody-drug conjugates, and bispecific antibodies in subsequent lines. While regimens like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC.

Keywords: Amivantamab; EGFR; Lazertinib; Osimertinib; chemotherapy.

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Conflict of interest statement

Prabhat Gautam Roy—None. Davida Reingold—None. Neha Pathak—None. Conso Molto—Honoraria from Merck and AstraZeneca. Nicholas Meti—Honoraria from AstraZeneca, Merck, Pfizer, Novartis, Gilead. Prabhat Singh Malik—None. Aarushi Gupta—None. Geordie Linford—Honoraria from Merck, Bayer, BMS, Knight Pharmaceuticals; consultancy—Pfizer. Abhenil Mittal—Honoraria from Merck, Astrazeneca, Gilead, Janssen, Novartis, Roche; Advisory Board for Gilead and Janssen.

Figures

Figure 1
Figure 1
(A) Mechanisms of resistance in EGFR-mutated advanced NSCLC [19,20]. (B) Mechanisms of acquired resistance in EGFR-mutated advanced NSCLC [21,22].
Figure 1
Figure 1
(A) Mechanisms of resistance in EGFR-mutated advanced NSCLC [19,20]. (B) Mechanisms of acquired resistance in EGFR-mutated advanced NSCLC [21,22].
Figure 2
Figure 2
Choosing second-line treatment.
See this image and copyright information in PMC

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