Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov 20;30(11):10033-10042.
doi: 10.3390/curroncol30110729.

Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion

Cesare Gridelli  1 , Marcello Tiseo  2   3 , Diego Luigi Cortinovis  4 , Maria Rita Migliorino  5 , Vito Barbieri  6 , Paolo Bironzo  7 , Alessandra Bearz  8 , Ilaria Attili  9 , Filippo de Marinis  9
Affiliations
Review

Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion

Cesare Gridelli et al. Curr Oncol. .

Abstract

Background: ALK tyrosine kinase inhibitors (TKIs) have revolutionized the treatment and largely improved the survival outcomes of patients with NSCLC harboring ALK rearrangements. Different ALK TKI compounds have demonstrated antitumor activity in these patients and are available in clinical practice. However, clinical expertise across countries varies according to local regulatory approval of different drugs, identifying multiple treatment scenarios to comply with international guidelines and clinical practice.

Methods: A virtual webinar was held on July 2023 to discuss the state of the art and future perspectives in the treatment of ALK rearrangement in advanced NSCLC in Italy. The faculty hosting the webinar was composed of eight medical oncologists from different regions of Italy with clinical expertise in treating patients with lung cancer. Live-shared notes were used to produce a report to serve as the basis of a review manuscript on the topic.

Results: Alectinib and brigatinib are the preferred front-line treatment options in Italy, pending approval of the front-line medicine lorlatinib, which would be considered among the choices. Due to a local regulatory limitation of second-line lorlatinib, which is not allowed after front-line brigatinib, alectinib is commonly the preferred front-line choice to follow a sequence of alectinib, followed by lorlatinib, followed by platinum plus pemetrexed chemotherapy. Age and performance status were not considered per se as clinical features influencing treatment choice. However, treatment compliance is deemed a relevant factor in decision making with regard to the number of pills to be administered. In general, given the availability of alternative choices, the spectrum of patients' comorbidities and polypharmacotherapy interactions should be taken into account in treatment selection according to the toxicity profile of each compound. In addition, several issues were debated with regard to improving treatment outcomes, including testing, brain metastases, and management of an oligoprogressive disease.

Conclusions: The treatment scenario of ALK-positive disease is dynamically evolving. Furthermore, not all FDA- and EMA-approved compounds are approved in Italy with the same indications. This influences therapeutic opportunities and increases the need for greater clinical expertise to help and guide treatment selection.

Keywords: ALK; alectinib; brigatinib; lorlatinib; lung cancer.

PubMed Disclaimer

Conflict of interest statement

C. Gridelli received honoraria as a speaker bureau or advisory board member or as a consultant from MSD, BMS, Roche, Astra Zeneca, Novartis, Pfizer, Menarini, Boehringer, Karyopharm, Eli Lilly, Amgen, Sanofi, GSK, and Boehringer Ingelheim. M. Tiseo received honoraria as a speaker bureau/scientific advisor from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda, Amgen, Merck, and Sanofi. M. Tiseo received research grants from Astra-Zeneca and Boehringer Ingelheim. D. Cortinovis received honoraria as a speaker bureau/scientific advisor from MSD, BMS, Astra Zeneca, Sanofi Genzyme, Seagen, Novartis, Amgen, Roche, and Takeda. M. R. Migliorino received honoraria as a speaker bureau/scientific advisor from MSD, Astra Zeneca, Sanofi Genzyme, Novartis, Roche, and Takeda. P. Bironzo received honoraria as speaker bureau or advisory board member from Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Astra Zeneca, Sanofi, Regeneron, Seagen, Janssen, Takeda, and Amgen. F. de Marinis received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Novartis, Takeda, Xcovery, and Roche. The other authors report no conflict of interests.

References

    1. Shaw A.T., Yeap B.Y., Mino-Kenudson M., Digumarthy S.R., Costa D.B., Heist R.S., Solomon B., Stubbs H., Admane S., McDermott U., et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 2009;27:4247–4253. doi: 10.1200/JCO.2009.22.6993. - DOI - PMC - PubMed
    1. Soda M., Choi Y.L., Enomoto M., Takada S., Yamashita Y., Ishikawa S., Fujiwara S., Watanabe H., Kurashina K., Hatanaka H., et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–566. doi: 10.1038/nature05945. - DOI - PubMed
    1. Koivunen J.P., Mermel C., Zejnullahu K., Murphy C., Lifshits E., Holmes A.J., Choi H.G., Kim J., Chiang D., Thomas R., et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin. Cancer Res. 2008;14:4275–4283. doi: 10.1158/1078-0432.CCR-08-0168. - DOI - PMC - PubMed
    1. Pacheco J.M., Gao D., Smith D., Purcell T., Hancock M., Bunn P., Robin T., Liu A., Karam S., Gaspar L., et al. Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non-Small Cell Lung Cancer. J. Thorac. Oncol. 2019;14:691–700. doi: 10.1016/j.jtho.2018.12.014. - DOI - PMC - PubMed
    1. Mok T., Camidge D.R., Gadgeel S.M., Rosell R., Dziadziuszko R., Kim D.W., Pérol M., Ou S.I., Ahn J.S., Shaw A.T., et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann. Oncol. 2020;31:1056–1064. doi: 10.1016/j.annonc.2020.04.478. - DOI - PubMed

Publication types

MeSH terms