An overview of alectinib hydrochloride as a treatment option for ALK positive non-small cell lung cancer

Introduction: Alectinib is a second-generation inhibitor of anaplastic lymphoma kinase (ALK) and RET. Phase III clinical trials have established its superiority to crizotinib in the first-line ALK inhibitor-naïve setting. Studies also support its use over chemotherapy in the post-crizotinib setting. It is currently one of several FDA- and EMA-approved ALK inhibitors, and it is listed as a preferred initial therapy for treatment-naïve ALK-positive non-small cell lung cancer (NSCLC).Areas covered: Herein, the authors provide the reader with details of the chemical structure, pharmacologic properties, resistance mutations, phase I, II, and III clinical trials, and safety profile of alectinib. Furthermore, the authors provide the reader with the expert opinion and future perspectives on the drug.Expert opinion: Alectinib compares favorably to other second-generation ALK inhibitors with regards to safety, tolerability, and efficacy. Based on currently available data, it is an appropriate first-line option. Ongoing studies will better resolve the ideal sequencing of ALK inhibitors in the treatment of ALK-positive NSCLC. READ ARTICLE

Expert Opinion on Pharmacotherapy DOI: 10.1080/14656566.2021.1948014

Authors: Schokrpur S, Hilburn V, Giustini N and Bazhenova L.

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer

Objectives: Alectinib demonstrated superior efficacy and a safety profile that compared favorably with crizotinib in treatment-naïve ALK+ non-small-cell lung cancer (NSCLC) in the phase III ALEX study. We present patient-reported outcomes (PROs) from ALEX to assess disease burden, treatment-related symptom tolerability, and health-related quality of life (HRQoL) with alectinib versus crizotinib. Conclusion: PRO data support the superior efficacy and tolerability of alectinib relative to crizotinib demonstrated in the ALEX study.

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Lung Cancer DOI: 10.1016/j.lungcan.2019.10.002

AUTHORS: Maurice Pérol, Nick Pavlakis, Evgeny Levchenko, Marco Platania, Julio Oliveira, Silvia Novello, Rita Chiari, Teresa Moran, Emmanuel Mitry, Eveline Nüesch, Ting Liu, Bogdana Balas, Krzysztof Konopa, Solange Peters

Clinical TrialsKirk SmithOctober 11, 2019Alectinib, ALK-positive, Crizotinib, NSCLC, Patient-reported outcomes, ALEX

Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study

The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX. Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy. READ ARTICLE

Annals of Oncology DOI:10.1093/annonc/mdy405

Authors: S.Gadgeel, S.Peters, T.Mok, A.T.Shaw, D.W.Kim, S.I.Ou, M.Pérol, A.Wrona, S.Novello, R.Rosell, A.Zeaiter, T.Liu, E.Nüesch, B.Balas, D.R.Camidge

Clinical TrialsKirk SmithNovember 1, 2018alectinib, ALK-positive, CNS, non-small cell lung cancer (NSCLC), ALEX

Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer

During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee–assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib).
As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC READ ARTICLE

the New England Journal of Medicine DOI:10.1056/NEJMoa1704795

Authors: Solange Peters, M.D., Ph.D., D. Ross Camidge, M.D., Ph.D., Alice T. Shaw, M.D., Ph.D., Shirish Gadgeel, M.D., Jin S. Ahn, M.D., Dong-Wan Kim, M.D., Ph.D., Sai-Hong I. Ou, M.D., Ph.D., Maurice Pérol, M.D., Rafal Dziadziuszko, M.D., Rafael Rosell, M.D., Ph.D., Ali Zeaiter, M.D., Emmanuel Mitry, M.D., Ph.D., Sophie Golding, M.Sc., Bogdana Balas, M.D., Johannes Noe, Ph.D., Peter N. Morcos, Pharm.D., and Tony Mok, M.D.

Clinical TrialsKirk SmithAugust 31, 2017Alectinib, Crizotinib, ALEX