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J Clin Oncol. 2015 Mar 20;33(9):1008-14. doi: 10.1200/JCO.2014.59.0489. Epub 2015 Feb 9.

Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses.

Author information

1
All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD. Gideon.Blumenthal@fda.hhs.gov.
2
All authors: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, White Oak, MD.

Abstract

PURPOSE:

To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) trials.

METHODS:

We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies.

RESULTS:

In the trial-level analysis, the association between PFS and ORR was strong (R(2) = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R(2) = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R(2) = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43).

CONCLUSION:

On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.

PMID:
25667291
PMCID:
PMC4356710
DOI:
10.1200/JCO.2014.59.0489
[Indexed for MEDLINE]
Free PMC Article

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