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 - van der Wekken, 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.
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.
KW - Non-small cell lung cancer
KW - KRAS mutation
KW - Chemotherapy
KW - Outcome
KW - Type of KRAS mutation
U2 - 10.1016/j.lungcan.2015.09.012
DO - 10.1016/j.lungcan.2015.09.012
M3 - Article
C2 - 26415993
SN - 0169-5002
VL - 90
SP - 249
EP - 254
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -