TY - JOUR
T1 - Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer
AU - Mellema, Wouter W.
AU - Masen-Poos, Lucie
AU - Smit, Egbert F.
AU - Hendriks, Lizza E. L.
AU - Aerts, Joachim G.
AU - Termeer, Arien
AU - Goosens, Martijn J.
AU - Smit, Hans J. M.
AU - van den Heuvel, Michel M.
AU - Wekken, van der, Anthonie J.
AU - Herder, Gerarda J. M.
AU - Krouwels, Frans H.
AU - Stigt, Jos A.
AU - van den Borne, Ben E. E. M.
AU - Haitjema, Tjeerd J.
AU - Staal-Van den Brekel, Agnes J.
AU - van Heemst, Robbert C.
AU - Pouw, Ellen
AU - Dingemans, Anne-Marie C.
PY - 2015/11
Y1 - 2015/11
N2 - Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens.Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved from hospital databases. Primary objective: to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation.Results: 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of ICRAS mutation were G12C (46%), G12V (20%) and G1 2D (10%). Platinum was combined with pemetrexed (n =334), taxanes (n = 68) or gemcitabine (n = 62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p <0.01). Patients treated with bevacizumab in addition to taxanes (n =38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR = 0.72, p = 0.02), but not OS (HR= 0.87, p = 0.41). In patients with G12V, significantly improved ORR (p <0.01) was observed for taxanes, but not PFS or OS. Patients with G1 2C or G12D mutation had comparable ORR, PFS and OS in all treatment groups.Conclusion: KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR Response to chemotherapy regimens was different in types of ICRAS mutation. Especially patients with G12V had better response to taxane treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
AB - Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens.Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved from hospital databases. Primary objective: to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation.Results: 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of ICRAS mutation were G12C (46%), G12V (20%) and G1 2D (10%). Platinum was combined with pemetrexed (n =334), taxanes (n = 68) or gemcitabine (n = 62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p <0.01). Patients treated with bevacizumab in addition to taxanes (n =38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR = 0.72, p = 0.02), but not OS (HR= 0.87, p = 0.41). In patients with G12V, significantly improved ORR (p <0.01) was observed for taxanes, but not PFS or OS. Patients with G1 2C or G12D mutation had comparable ORR, PFS and OS in all treatment groups.Conclusion: KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR Response to chemotherapy regimens was different in types of ICRAS mutation. Especially patients with G12V had better response to taxane treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
KW - Non-small cell lung cancer
KW - KRAS mutation
KW - Chemotherapy
KW - Outcome
KW - Type of KRAS mutation
KW - ENDOTHELIAL GROWTH-FACTOR
KW - K-RAS ONCOGENE
KW - FACTOR GENE-EXPRESSION
KW - FACTOR-RECEPTOR
KW - MUTATIONS
KW - ADENOCARCINOMA
KW - ACTIVATION
KW - DOCETAXEL
KW - PATHWAY
U2 - 10.1016/j.lungcan.2015.09.012
DO - 10.1016/j.lungcan.2015.09.012
M3 - Article
SN - 0169-5002
VL - 90
SP - 249
EP - 254
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -