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Review
. 2024 Aug;44(8):553-576.
doi: 10.1007/s40261-024-01379-7. Epub 2024 Jul 31.

Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer

Edurne Arriola  1 , Javier de Castro  2 , Rosario García-Campelo  3 , Beatriz Bernárdez  4 , Reyes Bernabé  5 , Jordi Bruna  6 , Manuel Dómine  7 , Dolores Isla  8 , Óscar Juan-Vidal  9 , Teresa López-Fernández  10 , Ernest Nadal  11 , Delvys Rodríguez-Abreu  12 , María Vares  13 , Úrsula Asensio  14 , Luis F García  14 , Enriqueta Felip  15
Affiliations
Review

Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer

Edurne Arriola et al. Clin Drug Investig. 2024 Aug.

Abstract

The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK-positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.

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Conflict of interest statement

Edurne Arriola has received speaking and/or advisory honoraria from Pfizer, Janssen, Sanofi, AstraZeneca, Bristol Myers Squibb, Lilly, Boehringer Ingelheim, Takeda, Roche, and MSD; and travel support from Takeda, Roche, and AstraZeneca. Javier de Castro has received research funding and educational fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, and Hoffmann-La Roche; honoraria or held advisory role for AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, GSK, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Hoffmann-La Roche, Sanofi, and Takeda. Rosario García-Campelo has received research funding and grant support from Roche, Pfizer, Merck Serono, and Bristol Myers Squibb and received honoraria or held advisory role for Pfizer, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sanofi, Lilly, Amgen, Janssen, Boehringer Ingelheim, AstraZeneca, Takeda, Regeneron, and Sanofi; and travel support from Roche, Takeda, Astra Zeneca, Roche, and MSD. Reyes Bernabé has received speaking and/or advisory honoraria from Pfizer, Janssen, Sanofi, AstraZeneca, Bristol Myers Squibb, Roche, Takeda, and Jannsen. Beatriz Bernárdez has received speaking and/or advisory honoraria from Pfizer, Janssen, Astellas, Sanofi, AstraZeneca, Bristol Myers Squibb, Merck, Daiichi Sankyo, Takeda, and MSD. Jordi Bruna has received personal consulting fees or congress travel support from Takeda, Eisai, CSL Behring, Pfizer, and Novocure. Manuel Dómine has received honoraria for advisory board/consultancy from AstraZeneca, Boehringer Ingelheim, Janssen Cilag, MSD, Pfizer, Roche, Sanofi, and Takeda; and honoraria for speaker from AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, and Takeda. Dolores Isla has received honoraria and held advisory role for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, F. Hoffmann-La Roche, Janssen, Lilly, Merck, MSD, Novartis, Pfizer, Sanofi, and Takeda. Óscar Juan received honoraria and held advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli Lilly, Takeda, and Janssen; and travel, support from Takeda and AstraZeneca. Teresa López-Fernández has received honoraria for advisory board/speaker from Philips, Pfizer, Bristol Myers Squibb, Janssen, Daichi Sankyo, Myocardial Solutions, AstraZeneca, Beigene, and Bayer. Ernest Nadal has received research funding and grant support from Roche, Pfizer, Merck-Serono, and Bristol Myers Squibb; received honoraria or held advisory role for Pfizer, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sanofi, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer Ingelheim, AstraZeneca, Qiagen, Pierre Fabre, Takeda, Regeneron, and Sanofi; and travel support from Roche, Takeda, and MSD. Delvys Rodríguez has received personal fees/honoraria for consultancy/advisory role and lectures from Roche/Genentech, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Merck Serono, Eli Lilly, Gilead, Sanofi, Regeneron, Incyte, Pfizer, Takeda, and Novartis; travel expenses from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Regeneron, and Novartis; and grant support for studies from Bristol Myers Squibb. María Vares has no conflicts of interest. Úrsula Asensio was a Pfizer employee when this manuscript was written. Luis F García is a Pfizer employee. Enriqueta Felip has received personal fees/honoraria for consultancy/advisory roles and speaker bureau from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peervoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Touch Oncology, and Turning Point Therapeutics and has been an independent member of the board for Grifols.

Figures

Fig. 1
Fig. 1
Recommendations for the management of hypercholesterolemia and hypertriglyceridemia. LDL low-density lipoprotein
Fig. 2
Fig. 2
Recommendations for the management of arterial hypertension
Fig. 3
Fig. 3
Recommendations for the management of hyperglycemia. GLP1-RA glucagon-like peptide-1 receptor agonist, HbA1c glycosylated hemoglobin, iSGLT2 sodium/glucose cotransporter 2 inhibitor
Fig. 4
Fig. 4
Recommendations for the management of neurological adverse events. Part 1: Before initiating lorlatinib treatment and how to assess toxicity during treatment. Part 2: After toxicity appears. MRI magnetic resonance imaging
Fig. 5
Fig. 5
Recommendations for the management of edema
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Fig. 6
Recommendations for the management of diarrhea, nausea, vomiting, and constipation. 5-HT3 5-hydroxytryptamine
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Fig. 7
Recommendations for the management of alterations in amylase or lipase levels
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Fig. 8
Recommendations for the management of interstitial lung disease or pneumonitis. COPD chronic obstructive pulmonary disease, CT computerized tomography, ECOG Eastern Cooperative Oncology Group, ICU intensive care unit, IFN interferon, TNF tumor necrosis factor
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