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. Wekken, van der, 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

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    23 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)249-254
    Number of pages6
    JournalLung Cancer
    Volume90
    Issue number2
    DOIs
    Publication statusPublished - Nov-2015

    Keywords

    • Non-small cell lung cancer
    • KRAS mutation
    • Chemotherapy
    • Outcome
    • Type of KRAS mutation
    • ENDOTHELIAL GROWTH-FACTOR
    • K-RAS ONCOGENE
    • FACTOR GENE-EXPRESSION
    • FACTOR-RECEPTOR
    • MUTATIONS
    • ADENOCARCINOMA
    • ACTIVATION
    • DOCETAXEL
    • PATHWAY

    Cite this