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F. Cecere



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-056 - The Elderly Patient Individualized Chemotherapy Trial (EPIC): A Randomized Phase III Multicenter Trial of Customized Chemotherapy versus Standard of Care for 1st Line Treatment of Elderly Patients with Advanced Non-Small-Cell Lung Cancer (ID 1117)

      09:30 - 09:30  |  Author(s): F. Cecere

      • Abstract

      Background
      This is an ongoing phase III multicenter randomized trial comparing first line pharmacogenomic-driven chemotherapy based on Excision-Repair-Cross-Complementing-1 (ERCC1), Ribonucleotide Reductase subunit M1 (RRM1) and Thymidylate Synthase (TS) gene expression, versus standard first line treatment in elderly patients (pts) with advanced non-small-cell lung cancer (NSCLC). Chemotherapy selection based on an individual patient’s molecular profile is a potentially promising approach to optimize efficacy with the already available cytotoxic drugs. In older pts this is particularly relevant owing to their rapid deterioration of symptoms and their increased propensity to suffer therapy-induced toxicity.

      Methods
      Pts aged >70 years, with ECOG Performance Status (PS) 0 or 1, previously untreated for stage IV NSCLC will be evaluated. In a 2:1 fashion, pts will be randomized to experimental arm (A) or standard arm (B). They must have measurable disease and EGFR negative mutational status. In arm A, treatment with single or dual-agent chemotherapy will be based on histology, ERCC1 (E), RRM1 (R) and TS (T) expression at the mRNA level. Expression of E, R and T is assessed by qRT-PCR on paraffin-embedded tumor specimens in a central laboratory. The cut off for high or low expression have been previously defined. Pts with squamous NSCLC who are: E low/R high will be treated with single agent carboplatin, E high/R low with single agent gemcitabine, E low/R low with carboplatin and gemcitabine and E high/R high with docetaxel or vinorelbine. In non-squamous NSCLC pts: E low/T high will be treated with carboplatin, E high/T low with pemetrexed, E low/T low with carboplatin and pemetrexed, E high/T high/R low with gemcitabine and E high/T high/R high with docetaxel or vinorelbine. In arm B treatment will be standard of care at the discretion of the care provider. The primary endpoint is overall survival (OS). The secondary endpoints are progression-free survival (PFS), disease response according to RECIST 1.1 and tolerability (using CTCAE version 4.0). Feasibility of treatment selection based on pharmacogenomic parameters will also be assessed. Treatment will continue to a maximum of 6 cycles if tolerated or until disease progression. Switch maintenance treatment is not allowed in either arm. Continuation maintenance (one or more of the agents used in the initial regimen) is allowed at the discretion of the investigator. Treatment upon progression is at the discretion of the care provider. Assuming an exponential survival distribution for both treatment arms and a median survival time of 8 months in the control arm we anticipate to detect an improvement of 3 months in the median survival time in the experimental arm. To have 90% power to detect a three-month improvement in median survival at a significance level of 5% (2-sided) and assuming a 10% failure rate in gene analyses or loss to follow up rate, a sample size of 567 patients is planned to be enrolled.

      Results
      Not Applicable

      Conclusion
      We hypothesize that such tailored approach will improve survival decreasing the exposure to ineffective toxic agents in advanced NSCLC elderly pts. To our knowledge this is the first pharmacogenomic-driven randomized trial in this population.

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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): F. Cecere

      • 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.