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Cited by 265

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Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-Cell Lung Cancer

Open access
Scagliotti, Giorgio, von Pawel, Joachim, Novello, Silvia, Ramlau, Rodryg, Favaretto, Adolfo, Barlesi, Fabrice, Akerley, Wallace, Orlov, Sergey, Santoro, Armando, Spigel, David, Hirsh, Vera, Shepherd, Frances A., Sequist, Lecia V., Sandler, Alan, Ross, Jeffrey S., Wang, Qiang, von Roemeling, Reinhard, Shuster, Dale, Schwartz, Brian·2015·Journal of Clinical Oncology

Abstract

Purpose: Tivantinib, a MET receptor tyrosine kinase inhibitor, demonstrated increased anticancer activity in preclinical and early clinical studies when combined with erlotinib. Our study aimed to confirm efficacy and safety of the combination in previously treated patients with non–small-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced nonsquamous NSCLC previously treated with one to two systemic regimens, including a platinum doublet, were randomly assigned at a 1:1 ratio to receive erlotinib 150 mg daily plus oral tivantinib 360 mg twice daily (E + T) or erlotinib plus placebo (E + P) until disease progression. Tumor specimens were evaluated for EGFR and KRAS mutations, MET expression, and MET gene amplification. The primary end point was overall survival (OS). Secondary and exploratory objectives included progression-free survival (PFS), OS in molecular subgroups, and safety. Results: The study enrolled 1,048 patients and was discontinued for futility at the interim analysis. OS did not improve with E + T versus E + P (median OS, 8.5 v 7.8 months, respectively; hazard ratio [HR], 0.98; 95% CI, 0.84 to 1.15; P = .81), even though PFS increased (median PFS, 3.6 v 1.9 months; HR, 0.74; 95% CI, 0.62 to 0.89; P < .001). Exploratory subgroup analyses suggested OS improvement in patients with high MET expression (HR, 0.70; 95% CI, 0.49 to 1.01). Most common adverse events occurring with E + T versus E + P were rash (33.1% v 37.3%, respectively), diarrhea (34.6% v 41.0%), asthenia or fatigue (43.5% v 38.1%), and neutropenia (grade 3 to 4; 8.5% v 0.8%). Conclusion: E + T was well tolerated and increased PFS but did not improve OS in the overall nonsquamous NSCLC population.

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Metadata

Authors
Scagliotti, G., von Pawel, J., Novello, S., Ramlau, R., Favaretto, A., Barlesi, F., Akerley, W., Orlov, S., Santoro, A., Spigel, D., Hirsh, V., Shepherd, F. A., Sequist, L. V., Sandler, A., Ross, J. S., Wang, Q., von Roemeling, R., Shuster, D., & Schwartz, B.
Venue
Journal of Clinical Oncology
Published
2015-08-20
Volume
33
Issue
24
Pages
2667-2674
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2160725767
Cited by
265
References
6
FWCI
33.78
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-Cell Lung Cancer. https://app.cochat.ai/papers/10.1200/jco.2014.60.7317
The paper
Scagliotti, G., von Pawel, J., Novello, S., Ramlau, R., Favaretto, A., Barlesi, F., Akerley, W., Orlov, S., Santoro, A., Spigel, D., Hirsh, V., Shepherd, F. A., Sequist, L. V., Sandler, A., Ross, J. S., Wang, Q., von Roemeling, R., Shuster, D., & Schwartz, B. (2015). Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2014.60.7317

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.