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  • br cMET br p value Total


    p-value Total
    Stage at diagnosis
    Performance Status (PS)
    Smoking status
    ALK mutation
    Adjuvant treatment
    cMET: cellular Mesenchymal Epithelial Transition factor, ALK: Anaplastic
    Lymphoma Kinase, LCLC: Large-Cell Lung Cancer, NOS: Non Otherwise Specified, CT: Chemotherapy, RT: Radiotherapy, sd: standard deviation.
    the present analysis. Regarding the adjuvant treatment regimen, data collection was feasible for 148 patients, of which 34.5% received Cis-platin/Vinorelbine, 54.7% Carboplatin/Vinorelbine, 9.4% Carboplatin/ Gemcitabine and 1.4% Carboplatin/Paclitaxel.
    3.2. Survival analyses
    The OS and PFS analyses for all the c-MET H-score quartiles failed to show any statistical significance (data not shown for 25- and 75-quartiles). Regarding the 50-quartile (c-MET H-score 20), we performed separate Kaplan-Meier OS and PFS analyses in the whole study popu-lation, in the subgroup of patients who received adjuvant treatment and in the subgroup of patients who did not receive any adjuvant treatment (Figs. 1 and Suppl. 2). We observed a crossover of the curves at 7.5 years in the whole study TAK-242 (Fig. 1a) and in patients not re-ceiving adjuvant treatment (Fig. 1c), something which was not seen for the subgroup of patients who received adjuvant treatment (Fig. 1b). A  Lung Cancer 133 (2019) 69–74
    similar pattern was observed in the PFS analyses (Suppl. Fig. 2).
    The univariate survival analysis for the whole study population, presented in Table 3, showed that younger age at diagnosis, female gender, lower stage and better PS were associated with prolonged OS, whereas the remaining variables showed a trend towards statistical significance in a varying manner. We observed no significant impact on OS for the 25- and 75- c-MET H-score quartiles (data not shown).
    The three different quartiles of c-MET H-score were examined se-parately with Cox-regression multivariate analyses (adjuvant treatment not initially included because of 209 patients with missing data, see Table 2). All other variables were included in these analyses. We ob-served no statistical significant impact on OS for the 25- and the 75-quartile (data not shown), but the 50-quartile (c-MET H-score 20) was an independent prognostic variable in the whole study population with
    a HR = 0.79 (95%CI: 0.64−0.97, p value = 0.022), together with gender, histology, stage and PS (Table 3). There was a larger number of missing data regarding the delivery of adjuvant treatment (see Table 2), compared to all other variables; therefore we performed two additional Cox-regression multivariate analyses, one including adjuvant therapy as a co-variate and one in the subgroup of patients who received adjuvant therapy. In the first ana-lysis, c-MET H-score ≥20 was an independent prognostic factor with a HR = 0.73 (95% CI: 0.57−0.94, p-value = 0.016), together with his-tology and stage with adjuvant treatment showing a strong trend in favour of longer OS (HR = 0.77 with 95% CI: 0.59–1.03, p-value = 0.081) (Table 3). In the multivariate subgroup analysis including only patients who received adjuvant therapy, we observed a stronger prog-nostic effect of c-MET H-score ≥20 with a HR = 0.61 (95% CI: 0.40−0.93, p-value = 0.022), with histology and stage retaining their independent prognostic value (Table 3). In all the above mentioned multivariate models, higher c-MET H-score as a continuous variable was an independent positive prognostic factor (Suppl. Table 1).
    Univariate and multivariate Cox-regression PFS analyses were un-dertaken in a similar manner to the OS analyses mentioned above. Although these analyses failed to show any statistically significant re-sult for c-MET as an independent prognostic variable, we observed a trend towards better PFS in patients with H-score ≥20. This trend was more profound in the multivariate analysis, including adjuvant treat-ment as a covariate (HR = 0.77, 95 %CI: 0.69–1.04, p-value = 0.085), and in the subgroup of patients who received adjuvant treatment (HR = 0.65, 95% CI: 0.41–1.04, p-value = 0.075) (Suppl. Table 1).