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Clinical Trial
. 2011 Sep 10;29(26):3567-73.
doi: 10.1200/JCO.2010.34.4929. Epub 2011 Aug 8.

A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer

Fred R Hirsch  1 , Fairooz Kabbinavar, Tim Eisen, Renato Martins, Fredrick M Schnell, Rafal Dziadziuszko, Katherine Richardson, Frank Richardson, Bret Wacker, David W Sternberg, Jason Rusk, Wilbur A Franklin, Marileila Varella-Garcia, Paul A Bunn Jr, D Ross Camidge
Affiliations
Clinical Trial

A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer

Fred R Hirsch et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2011 Oct 10;29(29):3948. Camidge, Ross [corrected to Camidge, D Ross]

Abstract

Purpose: Erlotinib prolongs survival in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a randomized, phase II study of erlotinib alone or intercalated with chemotherapy (CT + erlotinib) in chemotherapy-naïve patients with advanced NSCLC who were positive for epidermal growth factor receptor (EGFR) protein expression and/or with high EGFR gene copy number.

Patients and methods: A total of 143 patients were randomly assigned to either erlotinib 150 mg daily orally until disease progression (PD) occurred or to chemotherapy with paclitaxel 200 mg/m(2) intravenously (IV) and carboplatin dosed by creatinine clearance (AUC 6) IV on day 1 intercalated with erlotinib 150 mg orally on days 2 through 15 every 3 weeks for four cycles followed by erlotinib 150 mg orally until PD occurred (CT + erlotinib). The primary end point was 6-month progression-free survival (PFS); secondary end points included response rate, PFS, and survival. EGFR, KRAS mutation, EGFR fluorescent in situ hybridization and immunohistochemistry, and E-cadherin and vimentin protein levels were also assessed.

Results: Six-month PFS rates were 26% and 31% for the two arms (CT + erlotinib and erlotinib alone, respectively). Both were less than the historical control of 45% (P = .001 and P = .011, respectively). Median PFS times were 4.57 and 2.69 months, respectively. Patients with tumors harboring EGFR activating mutations fared better on erlotinib alone (median PFS, 18.2 months v 4.9 months for CT + erlotinib).

Conclusion: The feasibility of a multicenter biomarker-driven study was demonstrated, but neither treatment arms exceeded historical controls. This study does not support combined chemotherapy and erlotinib in first-line treatment of EGFR-selected advanced NSCLC, and the patients with tumors harboring EGFR mutations had a better outcome on erlotinib alone.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. AUC, area under the curve; AE, adverse event; CBDP, carboplatin; FISH, fluorescent in situ hybridization; IHC, immunohistochemistry; PD, progressive disease; UCCC, University of Colorado Cancer Center; UNK, unknown.
Fig 2.
Fig 2.
Thirty-six patients were fluorescent in situ hybridization negative, KRAS wild type (WT), and EGFR WT.
Fig 3.
Fig 3.
Kaplan-Meier plots of progression-free survival. (A) All patients; (B) EGFR wild-type patients; (C) EGFR mutant patients. CP, carboplatin/paclitaxel.
Fig 4.
Fig 4.
Kaplan-Meier plots of overall survival. (A) All patients; (B) EGFR wild-type patients; (C) EGFR mutant patients. CP, carboplatin/paclitaxel.
See this image and copyright information in PMC

References

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