Author of

• 12648

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12673

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    P3.11-025 - Prognostic and predictive role of KRAS mutations in patients with advanced Non Small Cell Lung Cancer treated with docetaxel or erlotinib as second line treatment in the Tailor trial (ID 2159)

    09:30 - 09:30  |  Author(s): E. Rulli
    • Abstract

    Background
    KRAS mutations in NSCLC are supposed to indicate a poor prognosis and poor response to anticancer treatment. However, such evidence is only drawn from retrospective series giving controversial results. Aim of this study is to prospectively assess the prognostic and predictive value of KRAS mutations in NSCLC patients treated with either erlotinib or docetaxel. This is a planned ancillary study within the TAILOR trial (NCT00637910 ).

    Methods
    Main eligibility criteria were a diagnosis of metastatic NSCLC, prior platinum-based chemotherapy and mutational status of EGFR and KRAS centrally assessed by direct sequencing in two independent laboratories. Only patients with wild-type EGFR and KRAS status assessed were randomly allocated to receive erlotinib or docetaxel until disease progression. Overall survival was the primary endpoint. To detect a 33% reduction in mortality with an 80% power (2 sided a=0.05), 220 patients were randomized. A subgroup analysis aimed at detecting particular subgroups of patients, where the differential effect of treatment could be highlighted, was planned.

    Results
    Overall, median survival and progression free survival were superior in the docetaxel arm compared to the erlotinib arm. Fiftyone out of 220 patients were found to be mutated in KRAS. No interaction effect was found according to KRAS status. In mutated KRAS the HR for OS was 0.81 (95%CI: 0.45-1.47) in favour of chemotherapy, and in wild type KRAS the HR was 0.79 (95%CI: 0.57-1.10); p value for interaction effect: 0.82. Similar pattern was found for PFS. In mutated KRAS patients the HR for PFS was 0.89 (95%CI: 0.51-1.57), while in wild type KRAS the HR was 0.68 (95%CI: 0.50-0.93), p value for interaction effect: 0.33. No evidence of prognostic effect of KRAS could be found. For OS, the HR for associations of mutated KRAS status and mortality was 1.24 (95%CI: 0.87-1.77; p=0.23); for PFS the HR was 1.00 (95%CI: 0.71-1.41; p=0.98)

    Conclusion
    Although the study is not sufficiently powered to test interaction for KRAS mutations, TAILOR results show that KRAS can be considered neither a prognostic nor a predictive factor in second line treatment in advanced NSCLC.