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L. Cirnes



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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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      P1.01-070 - KRAS Mutations: Does It Mean No Erlotinib? (ID 3065)

      09:30 - 17:00  |  Author(s): L. Cirnes

      • Abstract
      • Slides

      Background:
      KRAS mutations are the most common mutations in non-small cell lung cancer (NSCLC). Theoretically those patients are resistant to tyrosine kinase inhibitors, but studies are contradictory. The aim of this study was to compare second-line chemotherapy with docetaxel and erlotinib in patients with NSCLC, EGFR wild-type, depending on their KRAS status.

      Methods:
      We included 47 patients diagnosed with NSCLC, EGFR wild type, followed in a Lung Cancer Unit and treated with docetaxel or erlotinib as second-line chemotherapy. KRAS mutations in exon 12 and 13 were screened. Patients were divided in two arms: docetaxel arm and erlotinib arm. Time to progression to each second-line chemotherapy and overall survival after second-line chemotherapy was compared between patients with KRAS mutations and KRAS wild-type. In patients with KRAS mutations, time to progression and overall survival after second-line chemotherapy was compared between docetaxel and erlotinib.

      Results:
      87% were male, mean age 65±11 years, 77% smokers or ex-smokers, 81% non-squamous tumors, 70% stage IV at diagnosis. Analyzing all patients, there was no statistical difference regarding the time to progression and overall survival between patients with or without KRAS. 14 patients were in docetaxel arm and 33 patients in erlotinib arm. There were no statistical differences between arms regarding gender, smoking status, performance status and stage at diagnosis. Patients in docetaxel group were younger (60±9 years vs. 67±11 years, p=0.027). In docetaxel arm, 3 patients had KRAS mutations. We found no statistical differences between patients with or without mutations regarding time to progression and overall survival after docetaxel. In erlotinib arm, 7 patients had KRAS mutations. We found no statistical differences between patients with or without mutations regarding time to progression and overall survival after erlotinib. In patients with KRAS mutations, time to progression tends to be slightly higher in erlotinib arm (2 vs. 1 month, p=0.088) and overall survival after second-line chemotherapy seems to be similar.

      Conclusion:
      Unlike what is reported in some studies, we found no differences concerning KRAS status with respect to overall survival and time to progression. Moreover, it seems that there are no differences between docetaxel and erlotinib in second-line treatment. This questions the non-use of erlotinib in second-line treatment of KRAS mutated NSCLC patients.

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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-007 - KRAS Mutations in Lung Cancer: Prevalence and Outcomes (ID 2461)

      09:30 - 17:00  |  Author(s): L. Cirnes

      • Abstract
      • Slides

      Background:
      Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. The most commonly mutated oncogene in NSCLC encodes for KRAS and its mutations are usually associated to a poor prognosis. The aim of this study was to evaluate the prevalence and the prognosis of these mutations in a Portuguese cohort of patients with NSCLC, EGFR wild-type.

      Methods:
      We included 201 patients diagnosed with NSCLC, EGFR wild-type, followed in a Lung Cancer Unit. KRAS mutations in exon 12 and 13 were screened. Demographic and clinical data were analyzed. Overall survival, objective response to first-line chemotherapy and time to progression was evaluated in patients staged IIIB or IV at diagnosis.

      Results:
      173 (81.1%) were male, mean age 67±12 years, 40.1% smokers and 42.6% ex-smokers. At diagnosis, 9.1% were stage IA, 4.6% IB, 3% IIA, 2.5% IIB, 13.7% IIIA, 11.7% IIIB, 54.8% IV. 68.2% were adenocarcinoma and 21.4% squamous tumors. 79.5% was performance status 0-1. KRAS mutations were found in 46 (22.9%) patients and in 4.5% results were not valid. The most common mutations were G12C (41.8%) and G12V (26.1%). There was a statistically significant association between KRAS mutations and non-squamous histology (93.5% in KRAS mutated patients vs. 74.1% in KRAS wild-type patients, p=0.020) and a history of past or current smoking (93.4% vs. 78.4%, p=0.032). No statistical differences were found regarding age, gender, performance status or cancer stage at diagnosis. With respect to patients staged IIIB or IV at diagnosis, overall survival tended to be inferior in patients with KRAS mutations (median survival: 5 vs. 9 months, p=0.127). There was no statistical difference between groups regarding response to first-line chemotherapy and time to progression after first-line chemotherapy.

      Conclusion:
      The prevalence of KRAS mutation in this Portuguese cohort is consistent with results of similar studies in other countries (20-25%). KRAS mutations were associated to adenocarcinoma histology and smoking habits. Despite overall survival tending to be half in KRAS mutated IIIB/IV patients, this study showed little relevance as a prognostic marker. Thus, it is important to pursue the search for other molecular biomarkers that could be used in prognosis and even as therapy targets.

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