This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Felip E , Shaw AT , Bearz A , Camidge DR , Solomon BJ , Bauman JR , Bauer TM , Peters S , Toffalorio F , Abbattista A , Thurm H , Peltz G , Wiltshire R , Besse B
Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs
Ann Oncol. 2021 Feb 24
PMID: 33639216 URL: https://www.ncbi.nlm.nih.gov/pubmed/33639216
AbstractBACKGROUND: Lorlatinib, a potent, brain-penetrant, third-generation ALK tyrosine kinase inhibitor (TKI), has substantial activity against ALK-positive non-small-cell lung cancer (NSCLC). This study assessed the overall, intracranial, and extracranial efficacy of lorlatinib in ALK-positive NSCLC that progressed on second-generation ALK TKIs. PATIENTS AND METHODS: In the ongoing phase II study (NCT01970865), patients with ALK-positive advanced NSCLC treated with ≥1 prior second-generation ALK TKI ± chemotherapy were enrolled in expansion cohorts (EXP) based on treatment history. Overall, intracranial, and extracranial antitumor activity were assessed independently per modified RECIST v1.1. RESULTS: Of the 139 patients with ≥1 prior second-generation ALK TKI (EXP3B-5), 28 received one prior second-generation ALK TKI (EXP3B), 65 two prior ALK TKIs (EXP4), and 46 three prior ALK TKIs (EXP5). In EXP3B-5, the ORR (95% CI) was 39.6% (31.4-48.2), intracranial ORR (IC-ORR) was 56.1% (42.4-69.3), extracranial ORR (EC-ORR) was 36.7% (28.7-45.3), median duration of response (DOR) was 9.6 months (5.6-16.7; IC-DOR, 12.4 [6.0-37.1]; EC-DOR, 9.7 [6.1-33.3]), median PFS was 6.6 (5.4-7.4) months, and median OS was 20.7 months (16.1-30.3). In EXP3B, the ORR was 42.9% (24.5-62.8), the IC-ORR was 66.7% (29.9-92.5), and the EC-ORR was 32.1% (15.9-52.4). In EXP4-5, the ORR was 38.7% (29.6-48.5), the IC-ORR was 54.2% (39.2-68.6), and the EC-ORR was 37.8% (28.8-47.5). CONCLUSIONS: Lorlatinib had clinically meaningful intracranial and extracranial antitumor activity in the post-second-generation ALK TKI setting, with elevated intracranial versus extracranial ORR, particularly in patients with fewer lines of therapy.
Notes1569-8041 Felip, E Shaw, A T Bearz, A Camidge, D R Solomon, B J Bauman, J R Bauer, T M Peters, S Toffalorio, F Abbattista, A Thurm, H Peltz, G Wiltshire, R Besse, B Journal Article England Ann Oncol. 2021 Feb 24:S0923-7534(21)00129-0. doi: 10.1016/j.annonc.2021.02.012.