Shaw, Alice T., Yeap, Beow Y., Solomon, Benjamin J., Riely, Gregory J., Gainor, Justin, Engelman, Jeffrey A., Shapiro, Geoffrey I., Costa, Daniel B., Ou, Sai-Hong I., Butaney, Mohit, Salgia, Ravi, Maki, Robert G., Varella-Garcia, Marileila, Doebele, Robert C., Bang, Yung-Jue, Kulig, Kimary, Selaru, Paulina, Tang, Yiyun, Wilner, Keith D., Kwak, Eunice L., Clark, Jeffrey W., Iafrate, A. John, Camidge, D. Ross (2011) Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. The Lancet Oncology, 12 (11). pp. 1004-1012. ISSN 1470-2045
Abstract
BACKGROUND: ALK gene rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients with advanced, ALK-positive NSCLC. To assess whether crizotinib affects overall survival in these patients, we did a retrospective study comparing survival outcomes in crizotinib-treated patients in the trial and crizotinib-naive controls screened during the same time period. METHODS: We examined overall survival in patients with advanced, ALK-positive NSCLC who enrolled in the phase 1 clinical trial of crizotinib, focusing on the cohort of 82 patients who had enrolled through Feb 10, 2010. For comparators, we identified 36 ALK-positive patients from trial sites who were not given crizotinib (ALK-positive controls), 67 patients without ALK rearrangement but positive for EGFR mutation, and 253 wild-type patients lacking either ALK rearrangement or EGFR mutation. To assess differences in overall survival, we assessed subsets of clinically comparable ALK-positive and ALK-negative patients. FINDINGS: Among 82 ALK-positive patients who were given crizotinib, median overall survival from initiation of crizotinib has not been reached (95% CI 17 months to not reached); 1-year overall survival was 74% (95% CI 63-82), and 2-year overall survival was 54% (40-66). Overall survival did not differ based on age, sex, smoking history, or ethnic origin. Survival in 30 ALK-positive patients who were given crizotinib in the second-line or third-line setting was significantly longer than in 23 ALK-positive controls given any second-line therapy (median overall survival not reached [95% CI 14 months to not reached] vs 6 months [4-17], 1-year overall survival 70% [95% CI 50-83] vs 44% [23-64], and 2-year overall survival 55% [33-72] vs 12% [2-30]; hazard ratio 0·36, 95% CI 0·17-0·75; p=0·004). Survival in 56 crizotinib-treated, ALK-positive patients was similar to that in 63 ALK-negative, EGFR-positive patients given EGFR TKI therapy (median overall survival not reached [95% CI 17 months to not reached] vs 24 months [15-34], 1-year overall survival 71% [95% CI 58-81] vs 74% [61-83], and 2-year overall survival 57% [40-71] vs 52% [38-65]; p=0·786), whereas survival in 36 crizotinib-naive, ALK-positive controls was similar to that in 253 wild-type controls (median overall survival 20 months [95% CI 13-26] vs 15 months [13-17]; p=0·244). INTERPRETATION: In patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival compared with that of crizotinib-naive controls. ALK rearrangement is not a favourable prognostic factor in advanced NSCLC. FUNDING: Pfizer Inc, V Foundation for Cancer Research. TRIAL REGISTRATION: ClinicalTrials.gov NCT00585195.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > cancer types > lung cancer diseases & disorders > cancer > prognosis |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | 2011 |
| Date Deposited: | 21 Oct 2016 15:51 |
| Last Modified: | 21 Oct 2016 15:51 |
| PMCID: | PMC3328296 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33726 |
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