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Meta-Analysis
. 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

Gideon M Blumenthal  1 , Stella W Karuri  2 , Hui Zhang  2 , Lijun Zhang  2 , Sean Khozin  2 , Dickran Kazandjian  2 , Shenghui Tang  2 , Rajeshwari Sridhara  2 , Patricia Keegan  2 , Richard Pazdur  2
Affiliations
Meta-Analysis

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

Gideon M Blumenthal et al. J Clin Oncol. .

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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Study flow chart.
Fig 2.
Fig 2.
(A) Scatter plot of trial-level association between treatment effects on progression-free survival (PFS) and overall response rate (ORR). Trials with targeted treatments in molecularly enriched populations (n ≤ 500 patients per trial) are represented by red circles. (B) Scatter plot of trial-level association between treatment effects on PFS and ORR by study design. Add-on (A-O) trials are represented by blue circles and head-to-head (H-H) trials are denoted by gold circles.
Fig 3.
Fig 3.
(A) Scatter plot of trial-level association between treatment effects on overall survival (OS) and overall response rate (ORR). (B) Scatter plot of trial-level association between treatment effects on OS and progression-free survival (PFS). Trials with targeted treatments in molecularly enriched populations (n ≤ 500 patients per trial) are represented by red circles.
Fig 4.
Fig 4.
Kaplan-Meier estimates of (A) progression-free survival and (B) overall survival between responders and nonresponders. Exp, experimental; HR, hazard ratio.
See this image and copyright information in PMC

References

    1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. - PubMed
    1. Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM) A genomics-based classification of human lung tumors. Sci Transl Med. 2013;5:209ra153. - PMC - PubMed
    1. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175–180. - PubMed
    1. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311:1998–2006. - PMC - PubMed
    1. Khozin S, Blumenthal GM, Jiang X, et al. US Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. Oncologist. 2014;19:774–779. - PMC - PubMed

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