TY - JOUR
T1 - Biomarker analysis of the phase 3 TORCH trial for first line erlotinib versus chemotherapy in advanced non-small cell lung cancer patients
AU - Kim, Lucia
AU - Saieg, Mauro
AU - Di Maio, Massimo
AU - Gallo, Ciro
AU - Butts, Charles
AU - Ciardiello, Fortunato
AU - Feld, Ronald
AU - Cheng, Dengxiao
AU - Gebbia, Vittorio
AU - Burgio, Marco Angelo
AU - Alam, Yasmin
AU - Signoriello, Simona
AU - Rossi, Antonio
AU - Leighl, Natasha
AU - Maione, Paolo
AU - Morabito, Alessandro
AU - Liu, Geoffrey
AU - Tsao, Ming Sound
AU - Perrone, Francesco
AU - Gridelli, Cesare
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Biomarker analysis
KW - EGFR TKI
KW - NSCLC
KW - Predictive factors
KW - Prognostic factors
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U2 - 10.18632/oncotarget.15725
DO - 10.18632/oncotarget.15725
M3 - Article
AN - SCOPUS:85029059615
VL - 8
SP - 57528
EP - 57536
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 34
ER -