ALK in non-small cell lung cancer

23 EU-approved indications in non-small cell lung cancer need a ALK result: pembrolizumab (1st line, metastatic), nivolumab (1st line, metastatic), sugemalimab (1st line, metastatic), durvalumab (neoadjuvant, early), durvalumab (adjuvant, early), durvalumab (1st line, metastatic), serplulimab (1st line, advanced), crizotinib (1st line, advanced), crizotinib (2nd line, advanced), atezolizumab (1st line, metastatic), atezolizumab (2nd line, metastatic), atezolizumab (1st line, metastatic), lorlatinib (advanced), lorlatinib (2nd line, advanced), ipilimumab (1st line, metastatic), alectinib (adjuvant), alectinib (1st line, advanced), alectinib (2nd line, advanced), tremelimumab (1st line, metastatic), ceritinib (1st line, advanced), ceritinib (2nd line, advanced), brigatinib (advanced) and brigatinib (2nd line, advanced).

Histology

Disease setting

Approved indications, Non-small cell lung cancer
DrugBiomarker requirementRegimenSettingConditions
ALK fusion12
Alectinib
Alecensa
Monotherapy
Adj.
After complete tumour resection; High risk of recurrence
Alectinib
Alecensa
Monotherapy
1L
advanced
None
Ceritinib
Zykadia
Monotherapy
1L
advanced
None
Crizotinib
Xalkori
Monotherapy
1L
advanced
None
Alectinib
Alecensa
Monotherapy
2L
advanced
Previously treated with crizotinib
Atezolizumab
Tecentriq
+ bevacizumab, paclitaxel and carboplatin
2L
metastatic
Non-squamous only; After failure of appropriate targeted therapies
Brigatinib
Alunbrig
Monotherapy
2L
advanced
Previously treated with crizotinib
Ceritinib
Zykadia
Monotherapy
2L
advanced
Previously treated with crizotinib
Crizotinib
Xalkori
Monotherapy
2L
advanced
Previously treated
Lorlatinib
Lorviqua
Monotherapy
2L
advanced
Disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI
Brigatinib
Alunbrig
Monotherapy
Any line
advanced
No prior ALK inhibitor
Lorlatinib
Lorviqua
Monotherapy
Any line
advanced
Previously not treated with an ALK inhibitor
EGFR/ALK negative9
Durvalumab
Imfinzi
+ platinum-based chemotherapy
Neoadj.
early
Then adjuvant monotherapy after surgery; High risk of recurrence
Durvalumab
Imfinzi
Monotherapy
Adj.
early
After neoadjuvant durvalumab + platinum-based chemotherapy and surgical resection; High risk of recurrence
Atezolizumab
Tecentriq
EGFR/ALK-negative
+ bevacizumab, paclitaxel and carboplatin
1L
metastatic
Non-squamous only
Atezolizumab
Tecentriq
EGFR/ALK-negative
+ nab-paclitaxel and carboplatin
1L
metastatic
Non-squamous only
Durvalumab
Imfinzi
No sensitising EGFR mutations or ALK positive mutations
+ tremelimumab and platinum-based chemotherapy
1L
metastatic
None
No sensitising EGFR mutation or ALK translocation
+ nivolumab and 2 cycles of platinum-based chemotherapy
1L
metastatic
None
Nivolumab
Opdivo
No sensitising EGFR mutation or ALK translocation
+ ipilimumab and 2 cycles of platinum-based chemotherapy
1L
metastatic
None
EGFR/ALK-negative
+ pemetrexed and platinum chemotherapy
1L
metastatic
Non-squamous only
No sensitising EGFR mutations or ALK positive mutations
+ durvalumab and platinum-based chemotherapy
1L
metastatic
None
EGFR/ALK/ROS1 negative1
Serplulimab
Hetronifly
+ carboplatin and pemetrexed
1L
advanced
Non-squamous only; Not candidates for surgery or radiotherapy (if locally advanced)
EGFR/ALK/ROS1/RET negative1
No sensitising EGFR mutations, or ALK, ROS1 or RET genomic tumour aberrations
+ platinum-based chemotherapy
1L
metastatic
None

16 approvals for NSCLC need no biomarker and apply whatever the result. All approvals for NSCLC

See also

Label wording23

The sentence from section 4.1 of the SmPC that each indication above comes from.

  1. Pembrolizumab (Keytruda)
    KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous non-small cell lung carcinoma in adults whose tumours have no EGFR or ALK positive mutations.
  2. Nivolumab (Opdivo)
    OPDIVO in combination with ipilimumab and 2 cycles of platinum-based chemotherapy is indicated for the first-line treatment of metastatic non-small cell lung cancer in adults whose tumours have no sensitising EGFR mutation or ALK translocation.
  3. Sugemalimab (Cejemly)
    Cejemly in combination with platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic non-small-cell lung cancer (NSCLC) with no sensitising EGFR mutations, or ALK, ROS1 or RET genomic tumour aberrations.
  4. Durvalumab (Imfinzi)
    IMFINZI in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by IMFINZI as monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements (for selection criteria, see section 5.1).
  5. Durvalumab (Imfinzi)
    IMFINZI in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by IMFINZI as monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements (for selection criteria, see section 5.1).
  6. Durvalumab (Imfinzi)
    IMFINZI in combination with tremelimumab and platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic NSCLC with no sensitising EGFR mutations or ALK positive mutations.
  7. Serplulimab (Hetronifly)
    HETRONIFLY in combination with carboplatin and pemetrexed is indicated for the first-line treatment of adult non-squamous NSCLC patients with no EGFR, ALK or ROS1 positive mutations and who have:  locally advanced NSCLC who are not candidates for surgery or radiotherapy, or  metastatic NSCLC.
  8. Crizotinib (Xalkori)
    The first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC)
  9. Crizotinib (Xalkori)
    The treatment of adults with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC)
  10. Atezolizumab (Tecentriq)
    Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous NSCLC. In patients with EGFR-mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies (see section 5.1).
  11. Atezolizumab (Tecentriq)
    In patients with EGFR-mutant or ALK-positive NSCLC, Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies (see section 5.1).
  12. Atezolizumab (Tecentriq)
    Tecentriq, in combination with nab-paclitaxel and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous NSCLC who do not have EGFR-mutant or ALK-positive NSCLC (see section 5.1).
  13. Lorlatinib (Lorviqua)
    Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.
  14. Lorlatinib (Lorviqua)
    Lorviqua as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after: • alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy; or • crizotinib and at least one other ALK TKI.
  15. Ipilimumab (Yervoy)
    YERVOY in combination with nivolumab and 2 cycles of platinum-based chemotherapy is indicated for the first-line treatment of metastatic non-small cell lung cancer in adults whose tumours have no sensitising EGFR mutation or ALK translocation.
  16. Alectinib (Alecensa)
    Alecensa as monotherapy is indicated as adjuvant treatment following complete tumour resection for adult patients with ALK-positive NSCLC at high risk of recurrence (see section 5.1 for selection criteria).
  17. Alectinib (Alecensa)
    Alecensa as monotherapy is indicated for the first-line treatment of adult patients with ALK-positive advanced NSCLC.
  18. Alectinib (Alecensa)
    Alecensa as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib.
  19. Tremelimumab (Imjudo)
    IMJUDO in combination with durvalumab and platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitising EGFR mutations or ALK positive mutations.
  20. Ceritinib (Zykadia)
    Zykadia as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).
  21. Ceritinib (Zykadia)
    Zykadia as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib.
  22. Brigatinib (Alunbrig)
    Alunbrig is indicated as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.
  23. Brigatinib (Alunbrig)
    Alunbrig is indicated as monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib.