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S. Viteri



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    MINI 38 - Biology and Prognosis (ID 167)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI38.06 - FP1039/GSK3052230 with Chemotherapy in Patients with Fibroblast Growth Factor (FGF) Pathway Deregulated Squamous NSCLC or MPM (ID 2879)

      19:00 - 19:05  |  Author(s): S. Viteri

      • Abstract
      • Presentation
      • Slides

      Background:
      GSK3052230/FP1039 is a soluble fusion protein with the ECD of FGFR1c linked to the hinge and Fc regions of human IgG1 and acts as a ligand trap by sequestering FGFs involved in tumor growth and angiogenesis. In contrast to small molecule FGFR kinase inhibitors, GSK3052230 spares the hormonal FGF ligands, namely FGF19, 21 and 23. GSK3052230 combined with chemotherapy was efficacious in xenograft models of FGFR1-amplified NSCLC and malignant pleural mesothelioma (MPM) with FGF2 mRNA overexpression. A phase I monotherapy study determined 20mg/kg weekly as the maximum feasible dose (MFD) achieving the desired blood concentration, with no maximum tolerated dose (MTD) reached.

      Methods:
      This study (NCT01868022 funded by GSK) will evaluate the safety and efficacy of GSK3052230 weekly infusion in combination with paclitaxel + carboplatin in previously untreated FGFR1 amplified metastatic sqNSCLC (Arm A), in combination with docetaxel in FGFR1 amplified metastatic sqNSCLC that has progressed after at least 1 line of chemotherapy (Arm B), or in combination with pemetrexed + cisplatin in patients with untreated and unresectable MPM (Arm C). Each arm involves a dose escalation phase utilizing the 3+3 design, followed by an expansion phase up to 30 patients (pts). Key endpoints include the MTD/MFD of GSK3052230 with chemotherapy, safety, response rates and duration.

      Results:
      Thirty-four pts have been dosed with GSK3052230 at dose levels ranging from 5mg/kg to 20mg/kg in combination with chemotherapy across three Arms, n=15 (A), n=6 (B) and n=13 (C). Baseline characteristics: males/females 29/5; mean age 68.5 years; ECOG PS 0 (n=20), 1 (n=13), 2 (n=1). Most common AEs were: Arm A: asthenia, neutropenia; Arm B: neutropenia, diarrhea, rash; Arm C: decreased appetite, nausea, infusion reaction. Infusion reactions were seen in 8/34 (24%) pts (n=3 Grade (Gr)1, n=3 Gr2, n=2 Gr3). Serious AEs included: Arm A- neutropenia (n=4), fatigue (n=1), asthenia (n=1), fever (n=1), respiratory infection (n=1); Arm B- neutropenia (n=1), abdominal pain (n=1); Arm C-bowel perforation/ischemia (n=1), infusion reaction (n=1), elevated creatinine (n=1). No DLTs have been observed in sqNSCLC pts (Arms A and B). Three DLTs were reported in mesothelioma pts (Arm C 20mg/kg): Gr5 bowel perforation/ischemia, Gr4 elevated creatinine levels and Gr3 infusion reaction. MFD for Arm A is determined at 20mg/kg. Dose escalation is ongoing for Arms B and C. Preliminary PK results revealed no drug-drug interactions. At time of data-cutoff, 10 PR were observed among 23 patients evaluable for efficacy (ORR = 43%) and a clinical benefit rate of 78% with two ongoing subjects on study >300 days. Preliminary efficacy is as follows: Arm A (6 PR, 2 SD, 1 PD, 6= not-yet-evaluable (NE)), Arm B (4 SD, 1 PD, 1 NE), and Arm C (3 PR, 3 SD, 3 PD, 4 NE).

      Conclusion:
      GSK3052230 is in general well tolerated in combination with chemotherapy. The MFD for GSK3052230 is 20mg/kg in combination with paclitaxel + carboplatin in first line sqNSCLC patients. Toxicities typically associated with small-molecule FGFR inhibitors, namely hyperphosphatemia and retinal, nail, and skin changes, were not observed. The initial activity and safety profile of GSK3052230 ​warrant further study.

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    P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P2.03-005 - Surgical Resection after Definitive Chemoradiotherapy (ID 782)

      09:30 - 09:30  |  Author(s): S. Viteri

      • Abstract
      • Slides

      Background:
      Approximately, 30% of non-small-cell lung cancer (NSCLC) patients are diagnosed with locally advanced disease (IIIA-B). Treatment of these patients is controversial, with recommendations including definitive chemoradiotherapy, induction chemotherapy followed by surgery or induction chemoradiotherapy followed by surgical resection. Salvage surgery is defined as resection after high doses of radiation (>50Gy), planned as a primary curative intent, and usually more than 12 weeks after radiotherapy. Lung resection after high-dose radiotherapy has traditionally been avoided due to high rates of morbidity and mortality.

      Methods:
      The aim of this review is to analyze the outcome of patients referred to our institution for surgical resection after definitive chemoradiation. We reviewed 23 NSCLC patients who underwent surgical treatment after definitive chemoradiation between 2003 and 2014.

      Results:
      There were 15 men and eight women with a median age of 54.64 years (range 33-69 years). Fifteen patients were diagnosed with adenocarcinoma (65.2%), and the most frequent cTNM stage was T3N2M0 (34.8%) followed by T2N2M0 and T4N2M0. The type of surgical resection included five lobectomies, six bilobectomies and 12 pneumonectomies (seven right and five left pneumonectomies). Four patients showed a complete pathological response after treatment (pT0N0M0 17.4%). There was only one postoperative death due to a bronchopleural fistula. All patients received platinum-based chemotherapy and definitive radiotherapy, with a median dose of 65Gy (range 45-70Gy). Median time from radiotherapy to surgical resection was 8.28 months (0.9-35.47 months). Six patients suffered recurrence after surgery, three to a distant site and three local recurrences. Median disease free survival for the group of patients who relapsed after surgery was 7.7 months (3.9-17.5 months). Figure 1 Median overall survival was 88.3 months (CI 95% 57.6–118.9), with 1, 3 and 5 year survival rates of 87%, 74.5% and 66.3% respectively. Figure 2





      Conclusion:
      Salvage surgery after definitive chemoradiotherapy is feasible, with low postoperative complication rates and encouraging survival.

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