LORVIQUA

What it is

LORVIQUA contains lorlatinib. It is available as film-coated tablets in 25 mg and 100 mg strengths. Lorlatinib is an adenosine triphosphate-competitive, brain-penetrant, small molecule inhibitor of ALK and ROS1 tyrosine kinases that addresses mechanisms of resistance following previous treatment with ALK inhibitor therapy. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by a validated test.

Dosing overview

The recommended dose of LORVIQUA is 100 mg taken orally once daily. LORVIQUA may be taken with or without food. Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. Dose reduction levels are 75 mg once daily for the first reduction and 50 mg once daily for the second reduction. LORVIQUA should be permanently discontinued if the patient is unable to tolerate 50 mg taken orally once daily. A reduced dose of LORVIQUA is recommended in patients with severe renal impairment, for example a starting dose of 75 mg taken orally once daily.

Key safety warnings

LORVIQUA has been associated with increases in serum cholesterol and triglycerides. Serum cholesterol and triglycerides should be monitored before initiation, at 2, 4, and 8 weeks after initiating LORVIQUA, and periodically thereafter. Initiation or increase in the dose of lipid-lowering agents is required. Central nervous system effects have been observed in patients receiving LORVIQUA including psychotic effects, seizures, changes in cognitive function, mood, speech, and mental status changes. Dose modification or discontinuation may be required for those patients who develop CNS effects. PR interval prolongation and AV block events have been reported in patients receiving LORVIQUA. Monitor electrocardiogram prior to initiating LORVIQUA and monthly thereafter, particularly in patients with predisposing conditions to the occurrence of clinically significant cardiac events. Dose modification may be required for those patients who develop AV block. Severe or life-threatening pulmonary adverse drug reactions consistent with pneumonitis have occurred with lorlatinib. Any patient who presents with worsening of respiratory symptoms indicative of pneumonitis (for example dyspnoea, cough, and fever) should be promptly evaluated for pneumonitis. LORVIQUA should be withheld and/or permanently discontinued based on severity. Hypertension has been reported in patients receiving lorlatinib. Blood pressure should be controlled prior to initiation of lorlatinib. Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with lorlatinib. Hyperglycaemia has occurred in patients receiving lorlatinib. Fasting serum glucose should be assessed prior to initiation of lorlatinib and monitored periodically thereafter. There is a risk of fetal harm if exposed to LORVIQUA based on animal data and mechanism of action. Women of childbearing potential should be advised to avoid becoming pregnant while receiving LORVIQUA. Male fertility may be compromised during treatment with LORVIQUA. Men should seek advice on effective fertility preservation before treatment.

Contraindications

Hypersensitivity to lorlatinib or to any of the excipients. Concomitant use of strong CYP3A inducers with LORVIQUA is contraindicated due to the potential for serious hepatotoxicity.

PBS listing

LORVIQUA 100 mg and 25 mg tablets are each listed on the PBS with authority required restriction. The ex-manufacturer price is A$6272.46 per item.

Regulatory history

LORVIQUA received its first approval on 19 November 2019. The initial TGA approval was for treatment of patients with ALK-positive advanced NSCLC whose disease has progressed on specific prior ALK inhibitor therapies. This decision was based on tumour response rate and duration of response from a single-arm study, with ongoing approval subject to verification of clinical benefit in a confirmatory trial. In November 2019, PBAC recommended LORVIQUA as an authority required listing for ALK-positive metastatic NSCLC previously treated with ALK-TKIs, noting acceptable cost-effectiveness if cost-minimised to alectinib, with high unmet clinical need, broader mutational coverage, and intracranial activity. PBAC initially deferred consideration in July 2021 for locally advanced or metastatic ALK-positive NSCLC in treatment-naïve patients, then recommended this indication in December 2021.