Lorlatinib Salvages CNS Relapse in an ALK-Positive Non–Small-Cell Lung Cancer Patient Previously Treated With Crizotinib and High-Dose Brigatinib

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase‐positive non‐small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia—a case report

“…Previous reports showed that lorlatinib treatment is effective in patients with ALK‐ positive NSCLC, showing CNS relapse and impaired consciousness with poor PS upon failure of other ALK inhibitors [4–6]. However, few case studies have reported long‐term survivorship similar to this case.…”

Intracranial Response of ALK+ Non-Small-cell Lung Cancer to Second-line Dose-escalated Brigatinib After Alectinib Discontinuation Due to Drug-induced Hepatitis and Relapse After Whole Brain Radiotherapy Followed by Stereotactic Radiosurgery

“…4 Additionally, another patient received high-dose brigatinib because of CNS relapse after treatment with crizotinib preceded by cisplatin/pemetrexed/bevacizumab, cisplatin/vinorelbine/ cetuximab, erlotinib, and nanoparticle albumin-bound paclitaxel/ cetuximab. 5 The patient had successfully responded for 4 years to treatment in the initial phase I trial with brigatinib 240 mg once daily. However, further escalation of the brigatinib dose to 300 mg did not lead to a response at a later CNS relapse, and the patient instead achieved a new remission with lorlatinib.…”

Personalized Medicine in Oncology

“…The toxicity profile should be considered before the use of any TKI in the management of ALK-rearranged NSCLC, such as myalgia, edema, hepatotoxicity, interstitial lung disease/pneumonitis and bradycardia with alectinib and respiratory symptoms [264,265], vision change, amylase and lipase elevation, hypertension and similarly bradycardia with brigatinib. Although associated with undesirable toxicities including cognitive effects, mood changes, peripheral neuropathy and elevated triglycerides or cholesterol, lorlatinib is a third-generation TKI that has ample CNS penetration and has emerged as an effective agent with not only front-line activity, but efficacy at progression for multiple ALK resistance mutations from early-generation inhibitors [255,[266][267][268]. As with EGFR, the mechanism of resistance to ALK-inhibition should be sought with repeat tissue or liquid biopsy as targetable resistance mechanisms aside from ALK mutations may be identified [269].…”