LORVIQUA® (lorlatinib) as monotherapy is indicated for the treatment of patients with ALK+ metastatic NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK TKI therapy, or crizotinib and at least one other ALK TKI therapy1
Efficacy
ORR,PFS,DoR Individual Responses Prior ALK TKI CNS Efficacy
Guidelines ALK Resistance Mutations
Meet the challenge of ALK resistance mutations head on2
  • Data show that ALK resistance mutations were present in 56% of patients progressing on  second-generation ALK TKIs (n=48) *2​​​​​​​
  • Preclinical and clinical results demonstrate that LORVIQUA® has broad-spectrum potency against  a range of known ALK resistance mutations, including the hard-to-treat G1202R mutation2,3
In vitro ALK TKI IC50 values for the inhibition of ALK resistance mutations2
Adapted from  Gainor J  F,  et al. 2016.
Clinical results demonstrate the antitumor activity of LORVIQUA® against  ALK resistance mutations3
Individual responses of patients who have failed 1 prior 2nd-generation ALK TKI (EXP3B-5), according to ALK mutation status 3
Adapted from Shaw AT, et al. J Clin Oncol. 2019
*Ceritinib, 54%; alectinib, 53%; and brigatinib, 71%.  A  retrospective analysis of 103 repeat biopsies taken from ALK+ patients following progression on a 1st or 2nd-generation ALK inhibitor.2
In vitro data; absolute  IC50 values of crizotinib, ceritinib, alectinlb,  brigatinib and LORVIQUA® on cellular ALK phosphorylation in Ba/F3 cells harbouring wild-type EML4-ALK variant 1 or various  EML4-ALK resistance mutations are depicted. In Ba/F3 cells, ALKF1174C and ALKI1171T appear sensitive to ceritinib and alectinib, respectively; however, these mutations may not be susceptible to these  agents in vivo based upon previous clinical reports. 2
ALK mutation status determined by tissue genotyping.3
For Healthcare Professionals only
Abbreviations ALK+, Anaplastic lymphoma kinase positive;  CI, confidence interval; CNS, central nervous system; DoR, duration of response; IC50,half maximal inhibitory concentration;  NSCLC, non-small cell lung cancer; ORR, objective response rate; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.
References

1. Pfizer. LORVIQUA® (lorlatinib) Prescribing Information, Available from:  http://labeling.pfizer.com/ShowLabeling.aspx?id=12540 Accessed September 23,2021.
2. Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first-and second-generation ALK  inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118-1133.
3. Shaw AT, Solomon BJ, Besse  B, et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer.  J Clin Oncol. 2019;37(16):1370-1379.

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.

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® Safety Profile
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