Continuation of Lorlatinib in ALK-Positive NSCLC Beyond Progressive Disease

Ou, SHI; Solomon, BJ; Shaw, AT; Gadgeel, SM; Besse, B; Soo, RA; Abbattista, A; Toffalorio, F; Wiltshire, R; Bearz, A

Author(s): Ou, SHI; Solomon, BJ; Shaw, AT; Gadgeel, SM; Besse, B; Soo, RA; Abbattista, A; Toffalorio, F; Wiltshire, R; Bearz, A;
Details: Publication Year 2022-04,Volume 17,Issue #4,Page 568-577
Journal Title: Journal of Thoracic Oncology
Publication Type: Research article
Abstract: INTRODUCTION: Lorlatinib, a potent, selective third-generation ALK tyrosine kinase inhibitor (TKI), exhibited overall and intracranial antitumor activity in patients with ALK-positive NSCLC. METHODS: Retrospective analyses in the ongoing phase 2 trial (NCT01970865) investigated the clinical benefit of continuing lorlatinib beyond progressive disease (LBPD). Patients with previous crizotinib treatment as the only ALK TKI were group A (n = 28); those with at least one previous second-generation ALK TKIs were group B (n = 74). LBPD was defined as greater than 3 weeks of lorlatinib treatment after investigator-assessed progressive disease. Only patients with the best overall response of complete or partial response or stable disease were included. RESULTS: There were no major differences in baseline characteristics between groups. The median duration of treatment for patients who continued LBPD was 32.4 months (group A) and 16.4 months (group B) versus 12.5 months (group A) and 7.7 months (group B) for patients who did not continue LBPD. The median overall survival in group A was not reached (NR) in patients who continued LBPD versus 24.4 months (95% confidence interval [CI]: 12.1-NR); group B's median was 26.5 months (95% CI: 18.7-35.5) in patients who continued LBPD versus 14.7 months (95% CI: 9.3-38.5) in patients who did not continue LBPD. The median overall survival postprogression for groups A and B was NR (95% CI: 21.4-NR) and 14.6 months (95% CI: 11.2-19.2) in patients who continued LBPD and 8.0 months (95% CI: 1.5-NR) versus 5.3 months (95% CI: 2.8-14.3) in patients who did not continue LBPD. CONCLUSIONS: Continuing LBPD is a viable treatment strategy for select patients with ALK-positive NSCLC who progressed on lorlatinib.
Keywords: Aminopyridines; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology; Humans; Lactams; *Lactams, Macrocyclic/therapeutic use; *Lung Neoplasms/drug therapy/pathology; Protein Kinase Inhibitors/therapeutic use; Pyrazoles; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Alk+ nsclc; Lorlatinib; Lorlatinib beyond progressive disease; Postprogression treatment; Recist 1.1; Treatment beyond progression
Department(s): Medical Oncology
PubMed ID: 35026476
Publisher's Version: https://doi.org/10.1016/j.jtho.2021.12.011
Open Access at Publisher's Site: https://doi.org/10.1016/j.jtho.2021.12.011
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-02-14 04:06:14

Last Modified: 2025-02-14 04:08:15