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

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, ALEX Trial Investigators, Marco Platania

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.

METHODS: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.

RESULTS: 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).

CONCLUSIONS: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number9
DOIs
Publication statusPublished - Aug 31 2017

Fingerprint

Non-Small Cell Lung Carcinoma
Disease-Free Survival
Confidence Intervals
Central Nervous System
Advisory Committees
Disease Progression
crizotinib
anaplastic lymphoma kinase
CH5424802
Survival Rate
Research Personnel
Central Nervous System Diseases

Keywords

  • Adult
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents
  • Carbazoles
  • Carcinoma, Non-Small-Cell Lung
  • Central Nervous System Neoplasms
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Receptor Protein-Tyrosine Kinases
  • Young Adult
  • Clinical Trial, Phase III
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

Cite this

Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. / Peters, Solange; Camidge, D Ross; Shaw, Alice T; Gadgeel, Shirish; Ahn, Jin S; Kim, Dong-Wan; Ou, Sai-Hong I; Pérol, Maurice; Dziadziuszko, Rafal; Rosell, Rafael; Zeaiter, Ali; Mitry, Emmanuel; Golding, Sophie; Balas, Bogdana; Noe, Johannes; Morcos, Peter N; Mok, Tony; ALEX Trial Investigators ; Platania, Marco.

In: New England Journal of Medicine, Vol. 377, No. 9, 31.08.2017, p. 829-838.

Research output: Contribution to journalArticle

Peters, S, Camidge, DR, Shaw, AT, Gadgeel, S, Ahn, JS, Kim, D-W, Ou, S-HI, Pérol, M, Dziadziuszko, R, Rosell, R, Zeaiter, A, Mitry, E, Golding, S, Balas, B, Noe, J, Morcos, PN, Mok, T, ALEX Trial Investigators & Platania, M 2017, 'Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer', New England Journal of Medicine, vol. 377, no. 9, pp. 829-838. https://doi.org/10.1056/NEJMoa1704795
Peters, Solange ; Camidge, D Ross ; Shaw, Alice T ; Gadgeel, Shirish ; Ahn, Jin S ; Kim, Dong-Wan ; Ou, Sai-Hong I ; Pérol, Maurice ; Dziadziuszko, Rafal ; Rosell, Rafael ; Zeaiter, Ali ; Mitry, Emmanuel ; Golding, Sophie ; Balas, Bogdana ; Noe, Johannes ; Morcos, Peter N ; Mok, Tony ; ALEX Trial Investigators ; Platania, Marco. / Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 9. pp. 829-838.
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abstract = "BACKGROUND: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.METHODS: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.RESULTS: 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).CONCLUSIONS: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).",
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author = "Solange Peters and Camidge, {D Ross} and Shaw, {Alice T} and Shirish Gadgeel and Ahn, {Jin S} and Dong-Wan Kim and Ou, {Sai-Hong I} and Maurice P{\'e}rol and Rafal Dziadziuszko and Rafael Rosell and Ali Zeaiter and Emmanuel Mitry and Sophie Golding and Bogdana Balas and Johannes Noe and Morcos, {Peter N} and Tony Mok and {ALEX Trial Investigators} and Marco Platania",
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TY - JOUR

T1 - Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer

AU - Peters, Solange

AU - Camidge, D Ross

AU - Shaw, Alice T

AU - Gadgeel, Shirish

AU - Ahn, Jin S

AU - Kim, Dong-Wan

AU - Ou, Sai-Hong I

AU - Pérol, Maurice

AU - Dziadziuszko, Rafal

AU - Rosell, Rafael

AU - Zeaiter, Ali

AU - Mitry, Emmanuel

AU - Golding, Sophie

AU - Balas, Bogdana

AU - Noe, Johannes

AU - Morcos, Peter N

AU - Mok, Tony

AU - ALEX Trial Investigators

AU - Platania, Marco

PY - 2017/8/31

Y1 - 2017/8/31

N2 - BACKGROUND: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.METHODS: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.RESULTS: 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).CONCLUSIONS: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).

AB - BACKGROUND: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.METHODS: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.RESULTS: 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).CONCLUSIONS: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).

KW - Adult

KW - Aged, 80 and over

KW - Animals

KW - Antineoplastic Agents

KW - Carbazoles

KW - Carcinoma, Non-Small-Cell Lung

KW - Central Nervous System Neoplasms

KW - Disease-Free Survival

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Intention to Treat Analysis

KW - Kaplan-Meier Estimate

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Piperidines

KW - Protein Kinase Inhibitors

KW - Pyrazoles

KW - Pyridines

KW - Receptor Protein-Tyrosine Kinases

KW - Young Adult

KW - Clinical Trial, Phase III

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

U2 - 10.1056/NEJMoa1704795

DO - 10.1056/NEJMoa1704795

M3 - Article

C2 - 28586279

VL - 377

SP - 829

EP - 838

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 9

ER -