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X. He

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-055 - Prognostic Impact of KRAS Mutational Status in Patients with Advanced Lung Adenocarcinoma Receiving First-Line Cytotoxic Chemotherapy (ID 3212)

      09:30 - 17:00  |  Author(s): X. He

      • Abstract

      KRAS mutations are among the most commonly encountered mutations in lung adenocarcinoma. Although differential outcomes from cytotoxic agents according to histology have been shown in lung adenocarcinoma, the prognostic and predictive impact of KRAS mutational status is controversial. Recently, a study identified greater dependency on folate metabolism pathways in KRAS mutant (mt) compared to KRAS wildtype (wt) NSCLC (Moran et al, Mol Cancer Ther 2014, 6:1611-24). We sought to evaluate the clinical outcomes of patients with lung adenocarcinoma to first-line cytotoxic chemotherapy according to KRAS mutational status.

      This IRB-approved retrospective study involved patients from Roswell Park Cancer Institute (RPCI) diagnosed with inoperable stage III or IV lung adenocarcinoma from January 1, 2012 to December 31, 2013. Patients with documented KRAS mutational status who received chemotherapy were eligible. Patients with EGFR mutation or ALK translocation were excluded. The objective response (OR) to chemotherapy was assessed using RECIST version 1.1 criteria. The primary end points were Progression Free survival (PFS) and Overall Survival (OS). Secondary endpoint was the time to achieve OR. OS was estimated by the Kaplan-Meier method and compared using the Log-rank method. The association between study endpoints and variables of interest (age, gender, stage, ECOG performance status [PS], KRAS mutation status) were conducted with univariate and multiple Cox models. SAS version 9.4 (SAS Institute, Cary, NC) were used for statistical analyses. All tests were two-sided and performed at a nominal significance level of 0.05.

      A total of 123 patients were eligible for this analysis. In our study, 53 (42%) patients carried KRAS mutations. Majority of patients had stage IV cancer at presentation (74%). There was no difference in distribution of KRAS mutation status by the stage of disease at presentation. The most common first-line chemotherapy regimen was pemetrexed-based platinum combination (85%). When pemetrexed-based regimen was utilized as first-line therapy, univariate analysis showed correlation between KRAS status, gender, stage and PS with OS, favoring KRAS wt, female, stage III and PS 0, respectively. After controlling for other related covariates, only gender, stage and PS remain independently associated with better OS. Patients with KRAS wt had a longer median OS compared to KRAS mt patients (414 vs 249 days, p=0.027). PFS and time to OR were similarly better in KRAS wt group although these were not statistically significant. There was no imbalance in terms of second-line therapy between KRAS mt vs wt patients. There was no difference in study endpoints according to KRAS mutation status observed in patients who received taxane-based chemotherapy as first line treatment. There was also no difference in survival outcomes according to first-line treatment regimen used when patients were stratified according to KRAS mutation status.

      KRAS mutation status is not correlated with treatment outcomes in patients with advanced lung adenocarcinoma receiving first-line cytotoxic chemotherapy.