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O. Martelli



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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-023 - BE-Positive: Gefitinib in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. A combined retrospective and prospective analysis from Italian patients. (ID 1881)

      09:30 - 09:30  |  Author(s): O. Martelli

      • Abstract

      Background
      Advanced NSCLC patients have an extremely poor prognosis with a 5-year survival rate of less than 5%. In 2009, the European Medicines Agency approved gefitinib, a reversible EGFR tyrosine kinase inhibitor, at the dose of 250 mg daily for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR activating mutations. As the first-line EGFR mutation positive data at that time were mainly in Asian populations a prospective phase IV, open-label, single-arm study of first-line gefitinib in Caucasian patients was presented: this trial confirmed the activity and efficacy of gefitinib in 106 Caucasian patients (Douillard EMCTO 2013). In the same way, we initially collected retrospectively, continuing then prospectively, the data of NSCLC EGFR-mutation positive Italian patients treated with first-line gefitinib, with the aim to evaluate the therapeutic outcomes and the approaches beyond progression in a “real life population”.

      Methods
      We collected data of patients who started gefitinib from June 2009 until May 2013. Primary endpoint was the evaluation of first line outcomes, in terms of: objective response rate (ORR), duration of treatment, progression-free survival (PFS), overall survival (OS) and safety. Secondary endpoint is the evaluation of the outcomes beyond progression to gefitinib. Here we report the results of first-line gefitinib of a large number of Caucasian patients.

      Results
      Data of 203 patients from 23 Italian Institutions were collected. The main patients characteristics were: median age 67 (range: 33-87), male/female 76/127, ECOG performance status (PS) 0/1/2/3/4 in 89/92/18/2/2 patients, 90.6% adenocarcinoma (in our study the percentage of carcinoma non otherwise specified was 1.5%), never/former/current smoker in 129/64/10, del19/L858R/uncommon in 128/57/18. In one case a T790M mutation ex novo was found in association with the deletion of the exon 19 (not all the patients were tested for this mutation at baseline). A median time for obtaining the EGFR test result was 8-15 days (more than 30% of the patients got the results in less than one week). Patients evaluable at the time of data lock were 168, of these 3 (1.8%) patients achieved a complete response, 72 (42.9%) a partial response for an ORR of 44.7%, 54 (32.1%) patients were stable. Median treatment with gefitinib was 38 weeks. Main toxicities were: grade 3-4 skin rash and diarrhea in 1.8% and 4.2%, respectively. Treatment was definitely stopped due toxicity in 4.2% of patients. After progression in 5 cases a re-biopsy was performed and 94 (56%) received a second-line treatment.

      Conclusion
      BE-Positive is the first study reporting results of first-line gefitinib in a large "real life population" of Caucasian patients. Data were firstly collected in a retrospective fashion, than in a prospective way. This study shows that Caucasian patients reported lower ORR when indirectly compared to Asian counterparts, but this is probably due to the partial analysis of the patients, excluding at this time those who are still on treatment. However, the tolerability profile was excellent and the median time of treatment is quite overlapping to literature data. The outcomes of PFS, OS and treatment beyond gefitinib progression will be reported when mature.

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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
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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): O. Martelli

      • 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.