Fabrizio Tabbò1, Francesco Passiglia1, Silvia Novello2. 1. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, TO, Italy. 2. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, TO, Italy. silvia.novello@unito.it.
Abstract
PURPOSE OF REVIEW: Anaplastic lymphoma kinase (ALK) rearrangements represent a seldom event in non-small cell lung cancer (NSCLC). Given the oncogene alteration, ALK targeting represents the main therapeutic strategy. Here, we review evidence regarding ALK inhibitors (ALKi): clinical activity, safety profiles, financial costs, and biomarkers of efficacy. RECENT FINDINGS: During the past 10 years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients: crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers.
PURPOSE OF REVIEW: Anaplastic lymphoma kinase (ALK) rearrangements represent a seldom event in non-small cell lung cancer (NSCLC). Given the oncogene alteration, ALK targeting represents the main therapeutic strategy. Here, we review evidence regarding ALK inhibitors (ALKi): clinical activity, safety profiles, financial costs, and biomarkers of efficacy. RECENT FINDINGS: During the past 10 years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients: crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers.
Authors: Solange Peters; D Ross Camidge; Alice T Shaw; Shirish Gadgeel; Jin S Ahn; Dong-Wan Kim; Sai-Hong I Ou; Maurice Pérol; Rafal Dziadziuszko; Rafael Rosell; Ali Zeaiter; Emmanuel Mitry; Sophie Golding; Bogdana Balas; Johannes Noe; Peter N Morcos; Tony Mok Journal: N Engl J Med Date: 2017-06-06 Impact factor: 91.245
Authors: Neal I Lindeman; Philip T Cagle; Dara L Aisner; Maria E Arcila; Mary Beth Beasley; Eric H Bernicker; Carol Colasacco; Sanja Dacic; Fred R Hirsch; Keith Kerr; David J Kwiatkowski; Marc Ladanyi; Jan A Nowak; Lynette Sholl; Robyn Temple-Smolkin; Benjamin Solomon; Lesley H Souter; Erik Thunnissen; Ming S Tsao; Christina B Ventura; Murry W Wynes; Yasushi Yatabe Journal: J Mol Diagn Date: 2018-01-23 Impact factor: 5.568
Authors: Jason K Sicklick; Shumei Kato; Ryosuke Okamura; Maria Schwaederle; Michael E Hahn; Casey B Williams; Pradip De; Amy Krie; David E Piccioni; Vincent A Miller; Jeffrey S Ross; Adam Benson; Jennifer Webster; Philip J Stephens; J Jack Lee; Paul T Fanta; Scott M Lippman; Brian Leyland-Jones; Razelle Kurzrock Journal: Nat Med Date: 2019-04-22 Impact factor: 53.440
Authors: A Kron; C Alidousty; M Scheffler; S Merkelbach-Bruse; D Seidel; R Riedel; M A Ihle; S Michels; L Nogova; J Fassunke; C Heydt; F Kron; F Ueckeroth; M Serke; S Krüger; C Grohe; D Koschel; J Benedikter; B Kaminsky; B Schaaf; J Braess; M Sebastian; K-O Kambartel; R Thomas; T Zander; A M Schultheis; R Büttner; J Wolf Journal: Ann Oncol Date: 2018-10-01 Impact factor: 32.976