FYI on clinical studies and survival rate. Believe she is healing!

The Lancet Oncology, Volume 12, Issue 11, Pages 1004 - 1012, October 2011

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doi:10.1016/S1470-2045(11)70232-7Cite or Link Using DOI

Published Online: 19 September 2011

Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis

Original Text

Dr Alice T Shaw MD a , Beow Y Yeap ScD a, Benjamin J Solomon MD b, Gregory J Riely MD c, Justin Gainor MD a, Jeffrey A Engelman MD a, Geoffrey I Shapiro MD d, Daniel B Costa MD e, Sai-Hong I Ou MD f, Mohit Butaney BS d, Prof Ravi Salgia MD g, Robert G Maki MD c, Prof Marileila Varella-Garcia PhD h, Robert C Doebele MD h, Prof Yung-Jue Bang MD i, Kimary Kulig PhD j, Paulina Selaru MSPH j, Yiyun Tang PhD j, Keith D Wilner PhD j, Eunice L Kwak MD a, Jeffrey W Clark MD a, A John Iafrate MD k, D Ross Camidge MD h

Summary

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.