Real-world efficacy and safety of lorlatinib in treating advanced ALK-positive non–small cell lung cancer patients

Abstract

Anaplastic lymphoma kinase (ALK) translocation is a rare driver mutation in lung cancer. This study was aimed to report on the efficacy of lorlatinib in real-world practice and to evaluate the impact of prior ALK inhibitor treatments. We retrospectively evaluated patients with ALK-positive non-small cell lung cancer (NSCLC) treated with lorlatinib regarding its efficacy, the impact of prior ALK inhibitor treatments and the adverse events, in particular dyslipidemia. A total of 22 ALK-positive patients were analyzed. All patients had received at least one second-generation ALK inhibitor(s), while 12 patients had a history of crizotinib treatment. For lorlatinib, the objective response rate was 35.7%, and disease control rate was 64.3%. Their progression-free survival (PFS) was 6.2 months. With prior therapies, patients receiving only second-generation ALK inhibitor(s) treatment showed PFS longer than those with both crizotinib and second-generation ALK inhibitor(s) treatments (15.2 vs. 6.2 months). Moreover, patients who showed benefits from prior ALK inhibitor(s) also had a PFS longer than those who did not (6.5 vs. 3.5 months). Regarding adverse events, 94.7% of patients had dyslipidemia and 21.1% of them were in grade 3 or 4. None of these patients discontinued the treatment due to dyslipidemia.No acute complication occurred with dyslipidemia. The real-world efficacy of lorlatinib and adverse events were similar to those reported in clinical trials. Interestingly, the history and responses of prior ALK inhibitor treatments may influence the efficacy of subsequent lorlatinib treatment.

Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study

“…Lorlatinib efficacy in this context was also analyzed in several studies [ 23 , 24 , 25 , 26 ]. Lorlatinib was accorded marketing authorization for second-line treatment after failure of a first-line second-generation TKI, regardless of the existence of a resistance mechanism.…”

“…These observations are quite similar to ours and are further supported by real-life data. In a multicenter retrospective analysis of lorlatinib in 37 heavily pretreated, ALK + advanced NSCLC patients, median lorlatinib DOT was 4.4 months, with 43.2% ORR and median OS from lorlatinib onset lasting 10.2 months [ 24 ]. Another analysis of 22 patients in the same setting found 35.7% ORR and 64.3% DCR, with median PFS at 6.2 months.…”

“…Another analysis of 22 patients in the same setting found 35.7% ORR and 64.3% DCR, with median PFS at 6.2 months. PFS was longer for patients who benefited from prior ALKi(s) than those who did not (6.5 vs. 3.5 months, respectively) [ 24 ]. In a real-world analysis of 76 ALK + NSCLC patients enrolled in early or expanded access programs for lorlatinib in Asia and the United States, respective ORR and median PFS for those treated with <2 previous TKIs, 2 previous TKIs and 3 previous TKIs, were 42% and NR months, 35% and 11.2 months and 18% and 6.5 months [ 27 ].…”

“…At the end of the study, respective 3-year PFS determined by a blinded independent review committee was 43% vs. 19%, with a median OS not reached (NR) for either group. At present, several alternatives to crizotinib are available [ 10 , 11 , 12 , 13 , 14 , 15 ], rendering real-life data essential [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] to attempt to evaluate optimal therapeutic sequences [ 28 ].…”

Clinical research progress of lorlatinib in progressive non-small cell lung cancer

“…Besides, among patients who received second-generation ALK inhibitors, 50% to 70% developed secondary ALK resistance mutations [5]. A study was conducted prospectively to demonstrate the rate of incidents of brain metastases in NSCLC participants with ALK positivity who had not been given any treatment ranged from 26% to 38% [6]. According to the data from real-world studies, 70%-80% of individuals had brain metastases prior to receiving Lorlatinib [6].…”