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ESMO 2020: Lorlatinib Versus Crizotinib in First-Line Treatment of ALK-Positive NSCLC

By: Julia Fiederlein
Posted: Thursday, September 24, 2020

According to Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre, Melbourne, and colleagues, lorlatinib appears to provide longer progression-free survival than crizotinib in patients with ALK-positive non–small cell lung cancer (NSCLC). The interim data from the multicenter phase III CROWN study, which were presented during the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (Abstract LBA2), support the use of this third-generation ALK tyrosine kinase inhibitor as a new first-line treatment option for these patients.

In a 1:1 allocation ratio, untreated patients with ALK-positive stage IIIB or IV NSCLC were randomly assigned to receive either oral lorlatinib (n = 149) or crizotinib (n = 147). Of the 296 enrolled patients, 291 received study treatment. Patients were stratified based on their ethnicity and central nervous system metastasis status.

Progression-free survival by blinded independent central review was significantly longer with lorlatinib than with crizotinib (hazard ratio = 0.28; P < .001). The median progression-free survival was not estimable with lorlatinib and was 9.3 months with crizotinib. Compared with crizotinib, lorlatinib demonstrated improved progression-free survival by investigator, objective response, and intracranial objective response. The majority of patients (76%) achieved a complete response (n = 4) or a partial response (n = 109) after treatment with lorlatinib. The best overall response rate was 58% with crizotinib; no complete responses were observed, and 85 patients achieved a partial response.

Grade 3 to 4 adverse events were reported in 72.5% of the lorlatinib arm and in 55.6% of the crizotinib arm; adverse events leading to treatment discontinuation occurred in 6.7% and 9.2% of patients, respectively. In the lorlatinib arm, the majority of grade 3 to 4 adverse events were laboratory abnormalities, with lipid abnormalities occurring most frequently.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.



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