Summary of EGFR+ NSCLC treatment recommendations from international guidelines1,2

Please refer to the full guidelines as necessary for more information.1,2

European Society of Medical Oncology (ESMO)

Recommendations for stage IV lung carcinoma with EGFR-activating mutation1

Treatment sequencing Treatment options
First-line therapy

Patients with a sensitizing EGFR mutation should receive first-line EGFR TKIs (afatinib OR dacomitinib OR erlotinib OR gefitinib OR osimertinib)

  • Preferred: osimertinib
     
  • Other recommended options: afatinib OR dacomitinib OR erlotinib (± bevacizumab OR ± ramucirumab) OR gefitinib/carboplatin/pemetrexed
Subsequent therapy
following systemic progression on first-line EGFR TKI (not osimertinib)

All tumors with clinical evidence of EGFR TKI resistance, not previously treated with osimertinib, should be tested for presence of EGFR exon 20 T790M mutation

  • Exon 20 T790M+ and/or CNS involvement: osimertinib
     
  • Exon 20 T790M–:  platinum-based ChT OR carboplatin/paclitaxel/bevacizumab/atezolizumab*
Subsequent therapy
following progression on first-line osimertinib		 Platinum-based ChT OR carboplatin/paclitaxel/bevacizumab/atezolizumab*

*In the absence of contraindications to the use of immunotherapy after targeted therapies have been used.

 

National Comprehensive Cancer Network® (NCCN®)

Recommendations for patients with metastatic NSCLC and EGFR mutations (exon 19 deletion or L858R) discovered prior to first-line systemic therapy2†  

Treatment sequencing Treatment options
First-line therapy

Patients with an EGFR mutation should receive first-line EGFR TKIs (afatinib OR dacomitinib OR erlotinib OR gefitinib OR osimertinib)

  • Preferred: osimertinib
     
  • Other recommended options: afatinib OR erlotinib (± ramucirumab OR bevacizumab) OR dacomitinib OR gefitinib
Subsequent therapy
following progression on first-line osimertinib

Asymptomatic

Consider definitive local therapy (e.g. SABR or surgery) for limited lesions* and continue osimertinib

Symptomatic

  • CNS involvement: consider definitive local therapy (e.g. SRS) for limited lesions* and continue osimertinib
     
  • Systemic limited metastases:* consider definitive local therapy (e.g. SABR or surgery) and continue osimertinib OR initial treatment options for adenocarcinoma or squamous cell carcinoma
     
  • Systemic multiple lesions: initial treatment options for adenocarcinoma or squamous cell carcinoma
Subsequent therapy
following progression on first-line afatinib OR erlotinib (± ramucirumab OR bevacizumab) OR dacomitinib OR gefitinib

Asymptomatic

Consider definitive local therapy (e.g. SABR or surgery) for limited lesions* and switch to osimertinib (if T790M+) OR continue afatinib OR erlotinib (± ramucirumab OR bevacizumab) OR dacomitinib OR gefitinib

Symptomatic

  • CNS involvement: consider definitive local therapy (e.g. SRS) for limited lesions* and switch to osimertinib (if T790M+) OR continue afatinib OR erlotinib (± ramucirumab OR bevacizumab) OR dacomitinib OR gefitinib
     
  • Systemic limited metastases:* consider definitive local therapy (e.g. SABR or surgery) and continue afatinib OR erlotinib (± ramucirumab OR bevacizumab) OR dacomitinib OR gefitinib OR initial treatment options for adenocarcinoma or squamous cell carcinoma (if T790M-) OR osimertinib (if not previously given and T790M+)

Systemic multiple lesions

  • T790M+: osimertinib (if not given previously)
     
  • T790M–: initial treatment options for adenocarcinoma or squamous cell carcinoma 
Subsequent therapy
following progression on ≥2 EGFR TKIs

Initial treatment options for adenocarcinoma or squamous cell carcinoma
Consider afatinib AND cetuximab

*Limited number is undefined, but clinical trials have included 3 to 5 metastases.

†The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

 

Osimertinib is considered the preferred first-line option for patients with metastatic NSCLC and EGFR mutations (exon 19 deletion or L858R)2 

 
 
Recommendations for patients with metastatic NSCLC and EGFR Exon 20 insertion mutations discovered prior to first-line systemic therapy2†
 
Treatment sequencing Treatment options 
First-line therapy
Patients with an Exon 20 insertion mutation should receive first-line initial treatment options for adenocarcinoma (pembrolizumab + carboplatin + pemetrexed OR pembrolizumab + cisplatin + pemetrexed) or squamous cell carcinoma (pembrolizumab + carboplatin + paclitaxel OR pembrolizumab + carboplatin + albumin-bound paclitaxel)*
Subsequent therapy
following tumor response evaluation

Progression

Amivantamab-vmjw OR mobocertinib

Response or stable disease

Initial systemic therapy (with carboplatin or cisplatin) for 4–6 cycles administered prior to maintenance therapy, depending on patient tolerability
Subsequent therapy
following progression on second-line amivantamab-vmjw OR mobocertinib

Amivantamab-vmjw OR mobocertinib (whichever was not used previously) OR subsequent systemic therapy for adenocarcinoma or squamous cell carcinoma (nivolumab OR pembrolizumab OR atezolizumab)
Subsequent therapy
following second-line initial systemic therapy

Progression

Amivantamab-vmjw OR mobocertinib

Response or stable disease

Maintenance therapy for 2 years if patients have previously received first-line immunotherapy OR until disease progression if they have previously received second-line immunotherapy
Subsequent therapy
following progression on third-line maintenance therapy

Amivantamab-vmjw OR mobocertinib (whichever was not used previously)
Subsequent therapy
following progression on third- or fourth-line amivantamab-vmjw OR mobocertinib

Subsequent systemic therapy for adenocarcinoma or squamous cell carcinoma (nivolumab OR pembrolizumab OR atezolizumab)

*Only preferred Category 1 treatment recommendations are provided. Please refer to the full guidelines for more information.

†The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

Please note, all the treatments mentioned on this page may not be approved in respective countries.

 

LEARN ABOUT CLINICAL ENDPOINTS

ChT: chemotherapy; CNS: central nervous system; EGFR: epidermal growth factor receptor; ESMO: European Society for Medical Oncology; NCCN: National Comprehensive Cancer Network® (NCCN®); NSCLC: non-small-cell lung cancer; SABR: stereotactic ablative body radiotherapy; SRS: stereotactic radiosurgery; TKI: tyrosine kinase inhibitor.