CHEMOTHERAPY CHOISE FOR PATIENTS WITH KRAS MUTATED NSCLC

Lung Cancer. 2015 Nov;90(2):249-54. doi: 10.1016/j.lungcan.2015.09.012. Epub 2015 Sep 15.

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

Mellema WW1, Masen-Poos L2, Smit EF3, Hendriks LE4, Aerts JG5, Termeer A6, Goosens MJ7, Smit HJ8, van den Heuvel MM9, van der Wekken AJ10, Herder GJ11, Krouwels FH12, Stigt JA13, van den Borne BE14, Haitjema TJ15, Staal-Van den Brekel AJ16, van Heemst RC17, Pouw E18, Dingemans AM4.

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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="" abstracttext="" addition="" all="" and="" bevacizumab="" but="" comparable="" compared="" for="" g12c="" g12d="" g12v="" groups.="" had="" highest="" improved="" in="" mutation="" n="38)" not="" observed="" or="" orr="" os.="" os="" p="" patients="" pemetrexed="" pfs="" significantly="" taxanes="" the="" to="" treated="" treatment="" was="" with="">

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.