Canadian Perspectives Revisited: Consensus on the management of ALK-rearranged NSCLC

Inhibition of the anaplastic lymphoma kinase (ALK) oncogenic driver in advanced non-small cell lung carcinoma (NSCLC) improves survival. In 2016 and 2018, Canadian thoracic oncology specialists published consensus on the identification and treatment of ALK-rearranged patients, recommending use of first- and second-generation ALK inhibitors, as initial and subsequent treatment in the advanced setting. New scientific literature warrants a consensus update.

ALK inhibitor pivotal and phase III clinical trials were reviewed to assess benefits, risks, and implications relative to current Canadian guidance for ALK-rearranged NSCLC patients.

Updated Canadian recommendations for management of ALK-rearranged NSCLC:

• •
  Resected patients considered to be at high risk of recurrence (stage IB [tumors ≥ 4 cm] to IIIA) should receive alectinib as the new standard of care for adjuvant treatment.
• •
  Patients with treatment-naïve advanced disease should be treated with lorlatinib (preferred), alectinib or brigatinib.
• •
  Patients previously-treated with second-generation inhibitors should receive lorlatinib.
• •
  Patients progressing on crizotinib can be offered alectinib (preferred), brigatinib (preferred), lorlatinib or ceritinib.
• •
  Patients exhausting ALK-directed therapy options should be considered for pemetrexed-based chemotherapy or clinical trials.
• •
  Use of immunotherapy regimens is not recommended.
• •
  Patients with early and advanced stage NSCLC must undergo molecular testing for ALK rearrangements.

Our consensus recommendations highlight major developments in management of ALK-rearranged NSCLC and their relevance to the Canadian context. We strongly support upfront ALK testing, treatment of high-risk resected patients with adjuvant alectinib, and use of next-generation ALK inhibitors (lorlatinib, alectinib, brigatinib) as initial treatment of advanced patients.