Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

•In patients with ALK-rearranged NSCLC who received lorlatinib within the compassionate use program, the objective tumor response (OR) and disease control (DC) were observed in 43% and 94% cases, respectively.•Lorlatinib showed particularly high efficacy against brain metastases, with OR and DC for intracranial disease reaching 81% and 100%, respectively.•Patients with V.1 and V.3 ALK translocations had similar response to the therapy.•Complete lack of adverse events tended to correlate with poor outcome of lorlatinib treatment. Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug.