lung cancer

First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer

First-line lorlatinib was compared against crizotinib and advanced ALK-positive non-small cell lung cancer. lorlatinib is a third-generation inhibitor of anaplastic lymphoma kinase.  It first showed efficacy in patients that progressed on crizotinib. the CROWN trial was a randomized, phase 3 clinical trial, that was global, comparing lorlatinib versus crizotinib in 296 patients.  Patients had advanced non-small cell lung cancer, with an ALK driver mutation.  No prior therapy was allowed.  The primary endpoint was progression free survival.  It was assessed by blind independent central review.  Secondary endpoints included objective response rate and intracranial responses.  An interim analysis of efficacy was planned after 130 301 177 expected events of disease progression or death that occurred.  78% of patients in the lorlatinib group were alive without disease progression at 12 months.  This is in comparison to 39% of the crizotinib would.  The hazard ratio was 0.28, 95% confidence interval of 0.19–0.41 with a P value of less than 0.001.  An objective response rate occurred in 76% of patients in the lorlatinib  group and 58% in the crizotinib group.  Among those of measurable brain metastases, 82% and 23% respectively had intracranial responses.  71% of patients who received lorlatinib had an intracranial complete response.  The most common adverse events with lorlatinib were dyslipidemia, edema, weight gain, neuropathy, and cognitive changes. lorlatinib had more grade 3 or 4 adverse events, predominantly lipid levels, versus crizotinib, 72 versus 56%.  Discontinuation rates were 7% and 9% respectively.  The authors concluded ” In an interim analysis of results among patients with previously untreated advanced ALK-positive NSCLC, those who received lorlatinib had significantly longer progression-free survival and a higher frequency of intracranial response than those who received crizotinib.”