Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb 25;8(34):57528-57536.
doi: 10.18632/oncotarget.15725. eCollection 2017 Aug 22.

Biomarker analysis of the phase 3 TORCH trial for first line erlotinib versus chemotherapy in advanced non-small cell lung cancer patients

Lucia Kim  1   2 , Mauro Saieg  1   3 , Massimo Di Maio  4   5 , Ciro Gallo  6 , Charles Butts  7 , Fortunato Ciardiello  8 , Ronald Feld  9 , Dengxiao Cheng  9 , Vittorio Gebbia  10 , Marco Angelo Burgio  11 , Yasmin Alam  12 , Simona Signoriello  6 , Antonio Rossi  13 , Natasha Leighl  9 , Paolo Maione  13 , Alessandro Morabito  4 , Geoffrey Liu  9 , Ming-Sound Tsao  1 , Francesco Perrone  4 , Cesare Gridelli  13   14
Affiliations

Biomarker analysis of the phase 3 TORCH trial for first line erlotinib versus chemotherapy in advanced non-small cell lung cancer patients

Lucia Kim et al. Oncotarget. .

Abstract

Background: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses.

Methods: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting. Progression-free survival (PFS) was the primary end-point, overall survival, response rate and side effects (diarrhoea and skin toxicity) were secondary end-points. Interactions between biomarkers and treatment were studied with multivariable models (either Cox model or logistic regression). Statistical analyses accounted for multiple comparisons.

Results: At least one biomarker was assessed in 324 out of 760 patients in the TORCH study. EGFR mutation was more common in female (P = 0.0001), East Asians (P < 0.0001) and never smoker (P < 0.0001) patients; low MET protein expression by IHC (H-score <200) was more frequent in squamous (P < 0.00009) and ABCG2 C/A or A/A polymorphism was more frequent among East-Asian patients (P = 0.0003). A significant interaction was found for EGFR mutation in PFS and response rate analyses while no predictive effect on OS was found for any biomarker. No biomarker tested was prognostic for PFS and OS. No polymorphism was significantly associated with skin toxicity or diarrhea.

Conclusion: In the present study, beyond the known role of EGFR mutation, no other biomarker has predictive or prognostic role.

Keywords: EGFR TKI; NSCLC; biomarker analysis; predictive factors; prognostic factors.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST M.Tsao and F.Perrone have received research funding from Roche. G.Liu, C.Butts, F.Ciardiello, A.Morabito, F.Perrone and C.Gridelli have received honoraria from AstraZeneca, Boeringher Ingelheim and Roche. A. Rossi has received honoraria from AstraZeneca and Boeringher Ingelheim.

Figures

Figure 1
Figure 1. Forest plot of progression free survival by treatment arm and biomarkers
Hazard ratio (HR) < 1 means a lower risk of progression or death for patients treated with first-line erlotinib.
Figure 2
Figure 2. Forest plot of overall survival by treatment arm and biomarkers
Hazard ratio (HR) < 1 means a lower risk of death for patients treated with first-line erlotinib.
Figure 3
Figure 3. Forest plot of response by treatment arm and biomarkers
Odds ratio (OR) >1 means a higher probability of response for patients treated with first-line erlotinib.
See this image and copyright information in PMC

References

    1. Besse B, Adjei A, Baas P, Meldgaard P, Nicolson M, Paz-Ares L, Reck M, Smit EF, Syrigos K, Stahel R, Felip E, Peters S, Panel M, et al. 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014;25:1475–84. doi: 10.1093/annonc/mdu123. - DOI - PubMed
    1. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8. doi: 10.1016/S1470-2045(09)70364-X. - DOI - PubMed
    1. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57. doi: 10.1056/NEJMoa0810699. - DOI - PubMed
    1. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46. doi: 10.1016/S1470-2045(11)70393-X. - DOI - PubMed
    1. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12:735–42. doi: 10.1016/S1470-2045(11)70184-X. - DOI - PubMed