Update of the Blue Book: What's New in the Treatment of Metastatic NSCLC with an ALK Gene Mutation?
As of March 1, 2022, the 28th update of the Blue Book by the Czech Society for Oncology of ČLS JEP was released. Let's take a look at what changes it has brought compared to the previous version in the treatment of metastatic non-small cell lung cancer (NSCLC) with a driver mutation in the ALK gene.
Molecular Examination
The chapter on stage IV (T, N any, M1a,b,c) now begins with a section on the necessity of histological and predictive molecular examination of the tumor. Specifically, the examination of the mutation status of the EGFR gene, chromosomal translocations of the ALK and ROS1 genes, and immunohistochemical examination of PD-L1 expression is recommended.
The chapter also mentions testing using the next-generation sequencing (NGS) method, which comprehensively covers the mutation status at the DNA level (27 genes) and RNA (12 genes). NGS testing should be performed exclusively based on the indication of a multidisciplinary indication seminar within a comprehensive oncology center, at the oncologist's request and does not replace the above-mentioned predictive testing. It can be indicated both at the establishment of the primary diagnosis and during the course of the disease.
First-line Treatment of Patients with ALK Gene Translocation
Alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib are effective in the first line of treatment. However, only alectinib, brigatinib, and crizotinib are covered by health insurance.
The Blue Book newly mentions lorlatinib in the first-line treatment, as monotherapy for adult patients with ALK+ NSCLC, who have not previously been treated with another anaplastic lymphoma kinase (ALK) inhibitor. However, health insurance coverage has not yet been established for this drug in the first line.
For crizotinib in the first-line treatment, the recommendation no longer mentions the necessity of proving the EML4-ALK mutation, only the proof of mutation in the ALK gene. For brigatinib, which received reimbursement last year, the indication has been refined to patients who have not yet been treated with another ALK inhibitor. There has been no change for alectinib and ceritinib since last year, and it still holds that ceritinib in the first line is not covered by health insurance.
Second and Subsequent Lines of Treatment for ALK+ NSCLC
With the update of the Blue Book, the administration of tyrosine kinase inhibitors (TKI) associated with ALK in the second and subsequent lines of NSCLC treatment has not changed significantly. After progression on chemotherapy, crizotinib is indicated (when the EML4-ALK mutation is positive). After progression on crizotinib as first-line treatment, alectinib, brigatinib, ceritinib, and lorlatinib can be used. However, in this indication, only alectinib and ceritinib are covered by health insurance. After progression on alectinib or ceritinib as first-line treatment, or after progression on crizotinib and at least one other TKI, lorlatinib is suitable and has been granted temporary health insurance coverage in these indications.
No new developments have emerged in the options for managing failures of targeted TKI therapy. Atezolizumab is effective, regardless of the level of PD-L1 expression, as monotherapy or in combination with bevacizumab, paclitaxel, and carboplatin in patients with good performance status (PS 0-1) and without contraindications to immunotherapy. Pembrolizumab also appears to be effective as monotherapy in patients with PD-L1 expression ≥ 1%. It still holds that neither of these options is covered by health insurance. Immunotherapy coverage is available only for patients without driver mutations in the ALK and EGFR genes.
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Sources:
1. Malignant tumor of the bronchus, lung, pleura, and thymus (C34, C33, C37). In: Kiss I. (ed.). Blue Book of the Czech Society for Oncology, 28th update. Masaryk Oncology Institute, Brno, March 1, 2022. Available at: https://www.linkos.cz/files/modra-kniha/21/805.pdf
2. Malignant tumor of the bronchus, lung, pleura, and thymus (C34, C33, C37). In: Kiss I. (ed.). Blue Book of the Czech Society for Oncology, 27th update. Masaryk Oncology Institute, Brno, March 1, 2021.
3. Information on reimbursement of medicinal products as of May 29, 2022. SÚKL, 2022 Available at: www.sukl.cz/modules/medication/search.php
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