Wouter W Mellema1, Lucie Masen-Poos2, Egbert F Smit3, Lizza E L Hendriks4, Joachim G Aerts5, Arien Termeer6, Martijn J Goosens7, Hans J M Smit8, Michel M van den Heuvel9, Anthonie J van der Wekken10, Gerarda J M Herder11, Frans H Krouwels12, Jos A Stigt13, Ben E E M van den Borne14, Tjeerd J Haitjema15, Agnes J Staal-Van den Brekel16, Robbert C van Heemst17, Ellen Pouw18, Anne-Marie C Dingemans4. 1. Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands. 2. Department of Pulmonary Diseases, Jeroen Bosch hospital's-Hertogenbosch, Netherlands. 3. Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands. Electronic address: ef.smit@vumc.nl. 4. Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht, Netherlands. 5. Department of Pulmonary Diseases, Amphia hospital, Breda, Netherlands. 6. Department of Pulmonary Diseases, Canisius Wilhemina hospital, Nijmegen, Netherlands. 7. Department of Pulmonary Diseases, Gelre hospital, Zutphen, Netherlands. 8. Department of Pulmonary Diseases, Rijnstate hospital, Arnhem, Netherlands. 9. Department of Thoracic Oncology, NKI-AvL, Amsterdam, Netherlands. 10. Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. 11. Department of Pulmonary Diseases, St Antonius hospital, Nieuwegein, Netherlands. 12. Department of Pulmonary Diseases, Spaarne hospital, Hoofddorp, Netherlands. 13. Department of Pulmonary Diseases, Isala clinics, Zwolle, Netherlands. 14. Department of Pulmonary Diseases, Catharina hospital, Eindhoven, Netherlands. 15. Department of Pulmonary Diseases, Alkmaar Medical Center, Alkmaar, Netherlands. 16. Department of Pulmonary Diseases, Ziekenhuis groep Twente, Almelo, Netherlands. 17. Department of Pulmonary Diseases, Deventer hospital, Deventer, Netherlands. 18. Department of Pulmonary Diseases, Groene Hart hospital, Gouda, Netherlands.
Abstract
OBJECTIVES: As suggested by in-vitro data, we hypothesize that subtypes of KRAS 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 platinum-based 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 KRAS mutation were G12C (46%), G12V (20%) and G12D (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 G12C 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 KRAS mutation. Especially patients with G12V had better response to taxane treatment.
OBJECTIVES: As suggested by in-vitro data, we hypothesize that subtypes of KRAS 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 platinum-based 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 KRAS mutation were G12C (46%), G12V (20%) and G12D (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 G12C or G12D mutation had comparable ORR, PFS and OS in all treatment groups. CONCLUSION:KRAS mutated NSCLCpatients treated with taxane-based chemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment.
Authors: B Ricciuti; M Brambilla; A Cortellini; A De Giglio; C Ficorella; A Sidoni; G Bellezza; L Crinò; V Ludovini; S Baglivo; G Metro; R Chiari Journal: Clin Transl Oncol Date: 2019-07-22 Impact factor: 3.405
Authors: Anna Biernacka; Peter D Tsongalis; Jason D Peterson; Francine B de Abreu; Candice C Black; Edward J Gutmann; Xiaoying Liu; Laura J Tafe; Christopher I Amos; Gregory J Tsongalis Journal: Cancer Genet Date: 2016-03-18
Authors: Jacqueline V Aredo; Sukhmani K Padda; Christian A Kunder; Summer S Han; Joel W Neal; Joseph B Shrager; Heather A Wakelee Journal: Lung Cancer Date: 2019-05-15 Impact factor: 6.081