Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis

Abstract

In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for the ALK- and ROS1-positive groups, respectively. In the ALK-positive group, lorlatinib proved efficacy after both brigatinib and alectinib. Lorlatinib treatment was well tolerated. Later-line lorlatinib treatment can induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer.

Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study

“…13 Similar efficacy was also seen in smaller, real-life studies. 14,16 Although lorlatinib is not yet approved for use in ROS1þ NSCLC, our results strongly support lorlatinib as a salvage therapy after the failure of at least one ROS1 TKI in these patients.…”

Efficacy of different sequential patterns after crizotinib progression in advanced anaplastic lymphoma kinase‐positive non–small cell lung cancer

“…Additionally, 16 of 48 patients with first‐and second‐generation ALK inhibitor progression had significantly longer survival with sequential lorlatinib. Some prospective studies showed good clinical efficacy of lorlatinib in second‐generation ALK‐TKIs resistant patients 22–25 . Previous real‐world studies in Japan (WJOG9516L) and France (IFCT‐1302 CLINALK) demonstrated the importance of sequential therapy 26,27 .…”

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.…”

“…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 ].…”