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

2020 ◽  
Vol 13 (11) ◽  
pp. 371
Author(s):  
Maximilian J. Hochmair ◽  
Hannah Fabikan ◽  
Oliver Illini ◽  
Christoph Weinlinger ◽  
Ulrike Setinek ◽  
...  

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.

2020 ◽  
Author(s):  
David Heredia ◽  
Feliciano Barrón ◽  
Andrés F. Cardona ◽  
Saul Campos ◽  
Jerónimo Rodriguez-Cid ◽  
...  

Background: Brigatinib has demonstrated its efficacy as first-line therapy and in further lines for ALK-positive non-small cell lung cancer (NSCLC) patients; however, real-world data in Latin America are scarce. Methods: From January 2018 to March 2020, 46 patients with advanced ALK-positive NSCLC received brigatinib as second or further line of therapy in Mexico and Colombia. The primary endpoint was progression-free survival (PFS); secondary endpoint was time to treatment discontinuation (TTD). Results: At a median follow-up of 9.3 months, the median PFS was 15.2 months (95% CI: 11.6–18.8), and TTD was 18.46 months (95% CI: 9.54–27.38). The estimated overall survival at 12 months was 80%. Safety profile was consistent with previously published data. Conclusion: Brigatinib is an effective treatment for previously treated ALK-positive NSCLC patients in a real-world setting.


2021 ◽  
Vol 4 (10) ◽  
pp. e2126306
Author(s):  
Samantha Wilkinson ◽  
Alind Gupta ◽  
Nicolas Scheuer ◽  
Eric Mackay ◽  
Paul Arora ◽  
...  

2020 ◽  
Vol 31 ◽  
pp. S1400
Author(s):  
A. Kapoor ◽  
V. Noronha ◽  
V.M. Patil ◽  
A.S. Joshi ◽  
N. Menon ◽  
...  

2020 ◽  
Vol 31 ◽  
pp. S1044
Author(s):  
N. Saoudi Gonzalez ◽  
A. Navarro ◽  
G. Villacampa Javierre ◽  
A. Garcia-Alvarez ◽  
J.D.D. Assaf Pastrana ◽  
...  

2019 ◽  
Vol 22 (3) ◽  
pp. 322-331 ◽  
Author(s):  
Marscha S. Holleman ◽  
Carin A. Uyl-de Groot ◽  
Stephen Goodall ◽  
Naomi van der Linden

2013 ◽  
Vol 31 (31) ◽  
pp. 3987-3996 ◽  
Author(s):  
Justin F. Gainor ◽  
Alice T. Shaw

The success of tyrosine kinase inhibitors (TKIs) in select patients with non–small-cell lung cancer (NSCLC) has transformed management of the disease, placing new emphasis on understanding the molecular characteristics of tumor specimens. It is now recognized that genetic alterations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes of NSCLC that are highly responsive to genotype-directed TKIs. Despite this initial sensitivity, however, the long-term effectiveness of such therapies is universally limited by the development of resistance. Identifying the mechanisms underlying this resistance is an area of intense, ongoing investigation. In this review, we provide an overview of recent experience in the field, focusing on results from preclinical resistance models and studies of patient-derived, TKI-resistant tumor specimens. Although diverse TKI resistance mechanisms have been identified within EGFR-mutant and ALK-positive patients, we highlight common principles of resistance shared between these groups. These include the development of secondary mutations in the kinase target, gene amplification of the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant and ALK-positive patients alike, acquired resistance may also be a dynamic and multifactorial process that may necessitate the use of treatment combinations. We believe that insights into the mechanisms of TKI resistance in patients with EGFR mutations or ALK rearrangements may inform the development of novel treatment strategies in NSCLC, which may also be generalizable to other kinase-driven malignancies.


2021 ◽  
Vol 17 ◽  
Author(s):  
Mauro Daniel Spina Donadio ◽  
Audrey Cabral F Oliveira ◽  
Luciana Leite Moura ◽  
Victor Hugo Fonseca de Jesus ◽  
Tiago Cordeiro Felisimino ◽  
...  

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