Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis Journal Article
| Authors: | Shaw, A. T.; Yeap, B. Y.; Solomon, B. J.; Riely, G. J.; Gainor, J.; Engelman, J. A.; Shapiro, G. I.; Costa, D. B.; Ou, S. H. I.; Butaney, M.; Salgia, R.; Maki, R. G.; Varella-Garcia, M.; Doebele, R. C.; Bang, Y. J.; Kulig, K.; Selaru, P.; Tang, Y.; Wilner, K. D.; Kwak, E. L.; Clark, J. W.; Iafrate, A. J.; Camidge, D. R. |
| Article Title: | Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis |
| 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. © 2011 Elsevier Ltd. |
| Keywords: | epidermal growth factor; adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; aged; middle aged; survival rate; retrospective studies; gene mutation; major clinical study; overall survival; advanced cancer; drug efficacy; patient selection; antineoplastic agents; pyridines; united states; outcome assessment; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; proportional hazards models; cohort analysis; risk factors; wild type; time factors; risk assessment; protein kinase inhibitors; survival time; gene rearrangement; pyrazoles; australia; receptor protein-tyrosine kinases; cancer classification; clinical trials, phase i as topic; tumor gene; multicenter studies as topic; phase 1 clinical trial (topic); kaplan-meier estimate; multicenter study (topic); crizotinib; alk gene; clinical classification |
| Journal Title: | Lancet Oncology |
| Volume: | 12 |
| Issue: | 11 |
| ISSN: | 1470-2045 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2011-10-01 |
| Start Page: | 1004 |
| End Page: | 1012 |
| Language: | English |
| DOI: | 10.1016/s1470-2045(11)70232-7 |
| PROVIDER: | scopus |
| PUBMED: | 21933749 |
| PMCID: | PMC3328296 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 November 2011" - "CODEN: LOANB" - "Source: Scopus" |
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