Summary of ALK+ 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 next-generation ALK TKI therapy1

Treatment sequencing Treatment options
First-line therapy

Patients with ALK-rearranged NSCLC should receive first-line ALK TKI (alectinib OR brigatinib OR ceritinib OR crizotinib)

  • Alectinib and brigatinib have both demonstrated PFS improvement over crizotinib
     
  • CNS involvement: alectinib OR brigatinib OR ceritinib is preferred

Ensartinib has shown PFS improvement compared with frontline crizotinib, but is not EMA-approved

Subsequent therapy 
following systemic progression on first-line crizotinib

Patients with ALK-rearranged NSCLC should receive a next-generation ALK TKI as next-line therapy if not received previously (alectinib OR brigatinib OR ceritinib)

  • Crizotinib progression or intolerance: alectinib OR ceritinib is recommended
     
  • Crizotinib resistance: brigatinib is an option
     
  • CNS progression with crizotinib: treatment should be a next-generation ALK TKI

Ensartinib possesses high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases, but is not EMA-approved
Subsequent therapy
following systemic progression on ≥1 first-line ALK TKI (other than crizotinib)		 Lorlatinib is an option if available

 

Use of ALK TKIs is effective for treatment of patients with ALK+ NSCLC and CNS involvement, and evidence supports alectinib, brigatinib or ceritinib in this setting as first-line therapy.

 

National Comprehensive Cancer Network® (NCCN®)

Recommendations for patients with ALK+ biomarker discovered prior to first-line systemic therapy2

Treatment sequencing Treatment options
First-line therapy Patients with ALK-rearranged NSCLC should receive first-line ALK TKI (alectinib OR brigatinib OR ceritinib OR crizotinib OR lorlatinib)
 
  • Preferred: alectinib OR brigatinib OR lorlatinib
     
  • Other recommended option: ceritinib
     
  • Useful in some circumstances: crizotinib
Subsequent therapy
following progression on first-line alectinib OR brigatinib OR lorlatinib OR ceritinib

Asymptomatic

Consider definitive local therapy (e.g. SABR or surgery) for limited lesions* and continue alectinib OR brigatinib OR ceritinib OR lorlatinib

Symptomatic

  • CNS involvement: consider definitive local therapy (e.g. SRS) for limited lesions* and continue alectinib OR brigatinib OR ceritinib OR lorlatinib
     
  • Systemic limited metastases:* consider definitive local therapy (e.g. SABR or surgery) and continue alectinib OR brigatinib OR ceritinib OR lorlatinib
     
  • Systemic multiple lesions: lorlatinib (if not used previously) OR initial treatment options for adenocarcinoma or squamous cell carcinoma
Subsequent therapy
following progression on first-line crizotinib

Asymptomatic

Consider definitive local therapy (e.g. SABR or surgery) for limited lesions* and continue crizotinib OR switch to alectinib OR brigatinib OR ceritinib

Symptomatic

  • CNS involvement: consider definitive local therapy (e.g. SRS) for limited lesions* and switch to alectinib OR brigatinib OR ceritinib
     
  • Systemic limited metastases:* consider definitive local therapy (e.g. SABR or surgery) and continue crizotinib
     
  • Systemic multiple lesions: alectinib OR brigatinib OR ceritinib OR initial systemic therapy options for adenocarcinoma or squamous cell carcinoma
Subsequent therapy
following progression on ≥2 ALK TKIs		 Lorlatinib (if not used previously) OR initial treatment options for adenocarcinoma or squamous cell carcinoma

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

LEARN ABOUT EGFR

ALK: anaplastic lymphoma kinase; ChT: chemotherapy; CNS: central nervous system; EMA: European Medicines Agency; ESMO: European Society for Medical Oncology; NCCN: National Comprehensive Cancer Network®; NSCLC: non-small-cell lung cancer; PFS: progression-free survival; SABR: stereotactic ablative body radiotherapy; SRS: stereotactic radiosurgery; TKI: tyrosine kinase inhibitor.