Since 1997, EGFR tyrosine kinase inhibitors (EGFR-TKIs) have evolved from first-generation agents, such as gefitinib, erlotinib, and icotinib, to second-generation agents like afatinib and dacomitinib, now to third-generation agents, including osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib for EGFR L858R, sunvozertinib for EGFR exon 20 insertion (20ins), and zorifertinib for EGFR-sensitive mutation with brain metastases. Over the past 30 years, substantial advancements have been made in the comprehensive management of EGFR-mutant NSCLC. This systemic review provides the history of the development of EGFR-TKI therapy for NSCLC from 1997 to 2026, highlighting clinical milestones, emerging therapies, and future directions in this rapidly evolving field.

10 days ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR exon 20 insertion • EGFR exon 20 mutation

Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Conmana (icotinib) • Ameile (aumolertinib) • Vizimpro (dacomitinib) • Ivesa (firmonertinib) • Lazcluze (lazertinib) • Semena (befotertinib) • Zegfrovy (sunvozertinib) • Zorifer (zorifertinib) • Rui Bi Da (rezivertinib) • Sanrisso (rilertinib) • limertinib (ASK120067)

11d

Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment (clinicaltrials.gov)

P2, N=47, Recruiting, Samsung Medical Center | Not yet recruiting --> Recruiting

11 days ago

Enrollment open

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification

Tepmetko (tepotinib) • Lazcluze (lazertinib)

17d

61186372NSC2012: A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination with Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination with Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (2025-520730-28-00)

P1/2, N=118, Recruiting, Janssen Cilag International

17 days ago

New P1/2 trial

EGFR mutation • EGFR L858R • EGFR exon 19 deletion

Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • Rybrevant Faspro (amivantamab and hyaluronidase-lpuj)

19d

Real-world occurrence of severe gastrointestinal bleeding in patients receiving amivantamab plus lazertinib: A two-case series among 25 consecutive cases. (PubMed, Lung Cancer)

Both the patients received apixaban. These findings suggest that real-world patients, who are often older, treated in later lines of therapy, and using concomitant anticoagulants, may be more vulnerable to severe gastrointestinal complications than those enrolled in controlled clinical trials. Close monitoring of serum albumin levels and gastrointestinal symptoms is recommended to prevent potentially fatal complications.

19 days ago

Clinical • Journal • Real-world evidence

EGFR (Epidermal growth factor receptor)

EGFR mutation

Lazcluze (lazertinib)

21d

Overall survival for amivantamab plus lazertinib versus osimertinib as first-line treatment in Asian participants with EGFR-mutant advanced NSCLC: A MARIPOSA subset analysis. (PubMed, Lung Cancer)

Consistent with the overall population, amivantamab-lazertinib significantly improved OS versus osimertinib among Asian participants with previously untreated EGFR-mutated advanced NSCLC, making it the first regimen to improve survival among Asian patients.

21 days ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation

Tagrisso (osimertinib) • Lazcluze (lazertinib)

21d

PALOMA-2: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov)

P2, N=520, Recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2027 --> Aug 2028

21 days ago

Trial completion date

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR exon 20 mutation

Tagrisso (osimertinib) • carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • Rybrevant Faspro (amivantamab and hyaluronidase-lpuj)

25d

NeoLazer: Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer (clinicaltrials.gov)

P2, N=160, Recruiting, Yonsei University | Not yet recruiting --> Recruiting

25 days ago

Enrollment open

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion

carboplatin • pemetrexed • Lazcluze (lazertinib)

26d

Clinical implications of plasma EGFR T790M and ctDNA shedding across metastatic sites in plasma- or tissue-confirmed EGFR-mutant non-small cell lung cancer treated with lazertinib: a prospective multicenter cohort study. (PubMed, Transl Lung Cancer Res)

Liver and adrenal metastases occurred exclusively in plasma T790M-positive patients and were associated with markedly worse outcomes, consistent with a ctDNA-shedding phenotype. Bone metastasis was an adverse prognostic factor independent of plasma T790M, underscoring the combined prognostic impact of molecular and metastatic features.

26 days ago

Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR T790M • EGFR positive

Lazcluze (lazertinib)