Clinical Research Papers:
Biomarker analysis of the phase 3 TORCH trial for first line erlotinib versus chemotherapy in advanced non-small cell lung cancer patients
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Abstract
Lucia Kim1,12,*, Mauro Saieg1,13,*, Massimo Di Maio2,14,*, Ciro Gallo3,*, Charles Butts4, Fortunato Ciardiello5, Ronald Feld6, Dengxiao Cheng6, Vittorio Gebbia7, Marco Angelo Burgio8, Yasmin Alam9, Simona Signoriello3, Antonio Rossi10, Natasha Leighl6, Paolo Maione10, Alessandro Morabito2, Geoffrey Liu6,**, Ming-Sound Tsao1,**, Francesco Perrone2,** and Cesare Gridelli10,11,**
1 Department of Pathology, University Health Network, Princess Margaret Cancer Center and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
2 National Cancer Institute, G. Pascale Foundation, IRCCS, Naples, Italy
3 Department of Mental Health and Preventive Medicine, Chair of Statistics, Second University of Naples, Naples, Italy
4 Medical Oncology, Cross Cancer Institute, Edmonton, Canada
5 Medical Oncology, Second University, Naples, Italy
6 Division of Hematology and Oncology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada
7 Medical Oncology, Casa di Cura La Maddalena, Palermo, Italy
8 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy
9 Medical Oncology, Windsor Regional Cancer Centre, Windsor, Canada
10 Department of Oncology/Hematology, Division of Medical Oncology, “S.G. Moscati” Hospital, Avellino, Italy
11 On behalf of the TORCH Investigators
12 Department of Pathology, Inha University School of Medicine, Incheon, South Korea
13 Santa Casa Medical School, Sao Paulo, SP, Brazil
14 University of Turin, Turin, Italy
* Co-first author
** Co-last author
Correspondence to:
Cesare Gridelli, email:
Keywords: NSCLC, EGFR TKI, biomarker analysis, predictive factors, prognostic factors
Received: November 09, 2016 Accepted: February 01, 2017 Published: February 25, 2017
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.
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PII: 15725