Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

Wouter W Mellema; Lucie Masen-Poos; Egbert F Smit; Lizza E L Hendriks; Joachim G Aerts; Arien Termeer; Martijn J Goosens; Hans J M Smit; Michel M van den Heuvel; Anthonie J van der Wekken; Gerarda J M Herder; Frans H Krouwels; Jos A Stigt; Ben E E M van den Borne; Tjeerd J Haitjema; Agnes J Staal-Van den Brekel; Robbert C van Heemst; Ellen Pouw; Anne-Marie C Dingemans

doi:10.1016/j.lungcan.2015.09.012

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

Wouter W Mellema
, Lucie Masen-Poos
, Egbert F Smit
, Lizza E L Hendriks
, Joachim G Aerts
, Arien Termeer
, Martijn J Goosens
, Hans J M Smit
, Michel M van den Heuvel
, Anthonie J van der Wekken
, Gerarda J M Herder
, Frans H Krouwels
, Jos A Stigt
, Ben E E M van den Borne
, Tjeerd J Haitjema
, Agnes J Staal-Van den Brekel
, Robbert C van Heemst
, Ellen Pouw
, Anne-Marie C Dingemans

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	249-54
Number of pages	6
Journal	Lung Cancer
Volume	90
Issue number	2
DOIs	https://doi.org/10.1016/j.lungcan.2015.09.012
Publication status	Published - Nov 2015
Externally published	Yes

Keywords

Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Carcinoma, Non-Small-Cell Lung/drug therapy
Deoxycytidine/administration & dosage
Disease-Free Survival
Female
Guanine/administration & dosage
Humans
Lung Neoplasms/drug therapy
Male
Middle Aged
Mutation/drug effects
Organoplatinum Compounds/administration & dosage
Prognosis
Retrospective Studies
Taxoids/administration & dosage
ras Proteins/genetics
Gemcitabine

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10.1016/j.lungcan.2015.09.012

Cite this

Mellema, W. W., Masen-Poos, L., Smit, E. F., Hendriks, L. E. L., Aerts, J. G., Termeer, A., Goosens, M. J., Smit, H. J. M., van den Heuvel, M. M., van der Wekken, A. J., Herder, G. J. M., Krouwels, F. H., Stigt, J. A., van den Borne, B. E. E. M., Haitjema, T. J., Staal-Van den Brekel, A. J., van Heemst, R. C., Pouw, E., & Dingemans, A.-M. C. (2015). Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer. Lung Cancer, 90(2), 249-54. https://doi.org/10.1016/j.lungcan.2015.09.012

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title = "Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer",

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.",

keywords = "Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carcinoma, Non-Small-Cell Lung/drug therapy, Deoxycytidine/administration \& dosage, Disease-Free Survival, Female, Guanine/administration \& dosage, Humans, Lung Neoplasms/drug therapy, Male, Middle Aged, Mutation/drug effects, Organoplatinum Compounds/administration \& dosage, Prognosis, Retrospective Studies, Taxoids/administration \& dosage, ras Proteins/genetics, Gemcitabine",

author = "Mellema, \{Wouter W\} and Lucie Masen-Poos and Smit, \{Egbert F\} and Hendriks, \{Lizza E L\} and Aerts, \{Joachim G\} and Arien Termeer and Goosens, \{Martijn J\} and Smit, \{Hans J M\} and \{van den Heuvel\}, \{Michel M\} and \{van der Wekken\}, \{Anthonie J\} and Herder, \{Gerarda J M\} and Krouwels, \{Frans H\} and Stigt, \{Jos A\} and \{van den Borne\}, \{Ben E E M\} and Haitjema, \{Tjeerd J\} and \{Staal-Van den Brekel\}, \{Agnes J\} and \{van Heemst\}, \{Robbert C\} and Ellen Pouw and Dingemans, \{Anne-Marie C\}",

year = "2015",

month = nov,

doi = "10.1016/j.lungcan.2015.09.012",

language = "English",

volume = "90",

pages = "249--54",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

Mellema, WW, Masen-Poos, L, Smit, EF, Hendriks, LEL, Aerts, JG, Termeer, A, Goosens, MJ, Smit, HJM, van den Heuvel, MM, van der Wekken, AJ, Herder, GJM, Krouwels, FH, Stigt, JA, van den Borne, BEEM, Haitjema, TJ, Staal-Van den Brekel, AJ, van Heemst, RC, Pouw, E & Dingemans, A-MC 2015, 'Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer', Lung Cancer, vol. 90, no. 2, pp. 249-54. https://doi.org/10.1016/j.lungcan.2015.09.012

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 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.

AB - 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.

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Carcinoma, Non-Small-Cell Lung/drug therapy

KW - Deoxycytidine/administration & dosage

KW - Disease-Free Survival

KW - Female

KW - Guanine/administration & dosage

KW - Humans

KW - Lung Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Mutation/drug effects

KW - Organoplatinum Compounds/administration & dosage

KW - Prognosis

KW - Retrospective Studies

KW - Taxoids/administration & dosage

KW - ras Proteins/genetics

KW - Gemcitabine

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 -

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

Abstract

Keywords

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