Consensus Recommendations for Management and Counseling of Adverse Events Associated With Lorlatinib: A Guide for Healthcare Practitioners

Abstract

Resistance to first-and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and development and progression of central nervous system metastases remain significant issues in the treatment of ALK-positive non-small-cell lung cancer. Lorlatinib is a novel third-generation ALK TKI that is able to penetrate the blood-brain barrier and has broad-spectrum potency against most known resistance mutations that can develop during treatment with crizotinib and second-generation ALK TKIs. The safety profile of lorlatinib is distinct from those of other ALK TKIs. Adverse events are typically mild to moderate in severity, seldom result in permanent discontinuations, and are generally manageable through lorlatinib dose modifications and/or standard medical therapy. This article provides guidance to advanced practice providers (e.g., nurses, nurse practitioners, physician assistants) and oncology pharmacists for the clinical management of key lorlatinib-emergent adverse reactions (i.e., hyperlipidemias, central nervous system effects, bodyweight increase, edema, and peripheral neuropathy). As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted.

Nursing Management and Adverse Events in Thyroid Cancer Treatments with Tyrosine Kinase Inhibitors. A Narrative Review

“…The management of AEs depends on the level of severity [ 4 ]: a dose reduction may be sufficient for mild toxicity (≤1), while for grade 2 and 3 toxicities, medical therapy and interruption of treatment may be necessary, even permanently so in case of grade 4 toxicity. The contribution of a multidisciplinary healthcare professional team (HCPs) is recommended in the management of TKIs [ 44 ], as is the support of a caregiver in the early stages of the therapeutic pathway [ 45 ].…”

“…As widely indicated in cancer care, a multidisciplinary approach is strongly recommended in the diagnostic-clinical-therapeutic pathway of thyroid cancers, including the contribution of a senior nurse [ 38 ]. The contribution of a multidisciplinary healthcare practitioner team (HCPs) improves the management of TKIs [ 44 ], and places the basis of the essential therapeutic alliance [ 68 ], made up of sharing cognitive and emotional experiences, and promoting resilience in patients and the care team. The creation of a therapeutic alliance between the patient and the care team is essential to create a climate of trust and the sharing of objectives [ 69 ].…”

Podcast on the Management of Adverse Events Associated with Lorlatinib

“…TB: Well, I've had the chance to use lorlatinib for a long time; I got to take part in the first-in-human dosing of this drug, so I've had patients on it for over 7 years at this point. What we see when we look at the CROWN data specifically in that first-line population, half of the patients, or 49%, on lorlatinib did have to be dose modified [49% had AEs leading to dose interruption and 21% had AEs leading to dose reduction], but after dose modification only 7% of patients had to come off lorlatinib because of toxicity [7], so it may take a little bit more effort on our part to manage that, but it is manageable [21][22][23].…”

Constitutional Thinness: tALKing the tALK or wALKing the wALK?

“…As might be expected from the widespread expression of ALK in the CNS, Lorlatinib frequently produces a wide range of CNS adverse effects including disturbances of cognition, mood, and speech. Notably, unwanted weight gain, rather than weight loss, appears to be a relatively common side effect of the drug (Reed et al, 2020). These findings would tend to diminish enthusiasm for pursuing ALK inhibition as a therapeutic strategy for obesity.…”