LORVIQUA® (lorlatinib) as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) or for patients with ALK-positive metastatic NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI1
First Line Prior ALK TKI

Efficacy in the First Line

Study Design: LORVIQUA® in First-Line Treatment

LORVIQUA® is a third-generation ALK inhibitor that was evaluated in a global, open-label, randomised, multicenter, Phase 3 trial2–4*
The demographic characteristics of the overall study population were: median age 59 years (range: 26 to 90 years), age ≥65 years (35%), 59% female, 49% White, 44% Asian, and 0.3% Black. The majority of patients had adenocarcinoma (94%) and never smoked (59%). CNS metastases as determined by BICR neuroradiologists were present in 26% (n=78) of patients: of these, 30 patients had measurable CNS lesions.1
*Study B7461006; NCT03052608.
†Including recent (within the past year) or active suicidal ideation or behaviour.
‡Assessed by BICR according to RECIST v1.1.
BICR=Blinded Independent Central Review; BID=twice daily; CNS=central nervous system; ECOG PS=Eastern
Cooperative Oncology Group Performance Status; QD=once daily; RECIST v1.1=Response Evaluation Criteria in Solid Tumours version 1.1; TKI=tyrosine kinase inhibitor.

Superior Progression-Free Survival With LORVIQUA® vs Crizotinib

Adapted from Shaw et al. N Engl J Med. 2020;383(21):2018–2029.3

•     Median PFS for LORVIQUA® was not estimable. Probability of PFS at 12 months was 0.78 for LORVIQUA® (95% CI: 0.70–0.84)
​​​​​​​       and 0.39 for crizotinib (95% CI: 0.30–0.48)3**

At the data cutoff point OS data was not mature.

§The NCCN Guidelines® for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.
‖See the NCCN Guidelines for detailed recommendations, including other preferred options.
Primary endpoint.
#Based on 1-sided log-rank test.
**Shaw et al. N Engl J Med. 2020;383(21):2018–2029.
HR=hazard ratio; PFS=progression-free survival.

Overall and Intracranial Response Rates

Adapted from Shaw et al. N Engl J Med. 2020;383(21):2018–2029.3
††Assessed by BICR according to RECIST v1.1.
‡‡Intracranial response and duration of response were evaluated in a prespecified exploratory analysis of 30 patients with measurable CNS lesions at baseline.
CNS=central nervous system; ORR=overall response rate.
 

Time to Intracranial Progression§§ ‖‖

The secondary endpoint of intracranial time to progression was not part of the statistical testing hierarchy. The small patient numbers are a limitation to this analysis. In addition, the clinical relevance of these data is unknown because they do not include disease status in the rest of the body.
•    Percentage of patients who were alive without CNS progression at 12 months3‖
                -    96% (95% CI: 91–98) with LORVIQUA®
                -    60% (95% CI: 49–69) with crizotinib

§§Time from randomisation to the first objective progression of CNS disease (either new brain metastases or progression of existing brain metastases).3
‖ ‖ Shaw et al. N Engl J Med. 2020;383(21):2018–2029.
CNS=central nervous system
​​

​​​​​​​LORVIQUA® Efficacy

​​​​​​​LORVIQUA® Safety Profile
LORVIQUA® Dosing and Therapy
​​​​​​​Management
References 
1. Pfizer. LORVIQUA® (lorlatinib) Prescribing Information, Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=12540 Accessed 6 January 2022.
2. Recondo G, Facchinetti F, Olaussen KA, Besse B, Friboulet L. Nat Rev Clin Oncol. 2018;15(11):694-708. 
3. Shaw AT, Bauer TM, de Marinis F, et al; CROWN Trial Investigators. N Engl J Med. 2020;383(21):2018-2029.
4. Protocol for: Shaw AT, Bauer TM, de Marinis F, et al; CROWN Trial Investigators. N Engl J Med. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187.
5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V4.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 4, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warrantiesof 
​​​​​​​any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides. Serum cholesterol and triglycerides should be monitored before the initiation of lorlatinib; 2, 4, and 8 weeks after initiating lorlatinib, and periodically thereafter. Initiation, or increase in the dose, of lipid-lowering agents is required.
Central nervous system (CNS) effects have been observed in patients receiving lorlatinib including seizures, psychotic effects, changes in cognitive function, mood (including suicidal ideation), mental status, sleep, and speech. Dose modification or discontinuation may be required for those patients who develop CNS effects.
PR interval prolongation and atrioventricular (AV) block events have been reported in patients receiving lorlatinib. Monitor electrocardiogram (ECG) prior to initiating lorlatinib 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.
Elevations of lipase and/or amylase have occurred in patients receiving lorlatinib. Median time of occurrence of increase in serum lipase and amylase is 70 days (range: 7 days to 696 days) and 41 days (range: 7 days to 489 days), respectively. Risk of pancreatitis should be considered in patients receiving lorlatinib due to concomitant hypertriglyceridemia and/or a potential intrinsic mechanism. Patients should be monitored for lipase and amylase elevations prior to the start of lorlatinib treatment and regularly thereafter as clinically indicated.
Severe or life threatening pulmonary adverse drug reactions consistent with ILD/pneumonitis have occurred with lorlatinib. Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough and fever) should be promptly evaluated for ILD/pneumonitis. Lorlatinib 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 the initiation of lorlatinib. Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with lorlatinib. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Hyperglycemia has occurred in patients receiving lorlatinib. Fasting serum glucose should be assessed prior to the initiation of lorlatinib and monitored periodically thereafter. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Concomitant use of any strong CYP3A inducer is contraindicated. Any strong CYP3A inducers have to be discontinued for at least 3 plasma half-lives of the strong CYP3A inducer before lorlatinib treatment is started. No clinically meaningful changes in liver function tests were seen in healthy subjects after receiving a combination of lorlatinib with the moderate CYP3A inducer modafinil.
Women of childbearing potential should be advised to avoid getting pregnant while receiving lorlatinib. Male fertility may be compromised during treatment with lorlatinib. Men should seek advice on effective fertility preservation before treatment.
Click here for LORVIQUA® Prescribing Information

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