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A. Sosa

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    ORAL 18 - Non PD1 Immunotherapy and Angiogenesis (ID 114)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL18.05 - Early Predictive Value of Perfusion-Computed Tomography (pCT) in Advanced NSCLC Patients Treated with Bevacizumab: IMPACT Trial (ID 2268)

      10:45 - 12:15  |  Author(s): A. Sosa

      • Abstract
      • Presentation
      • Slides

      The use of targeted drugs has implied the development of new imaging techniques able to assess in vivo processes as part of antitumor response. Functional imaging techniques may be more appropriate to study changes in vascularization parameters such as blood flow (BF), blood volume (BV) and permeability (PMB) after treatment with antiangiogenics. Perfusion-computed tomography (pCT) could be a useful technique to predict non-small cell lung cancer (NSCLC) (pts) that most benefit from antiangiogenic therapy by assessing early variations of perfusion parameters.

      IMPACT (NCT02316327) is an ongoing open-label, single arm phase II/IV study to evaluate the predictive value of early perfusion changes in pts diagnosed with advanced non-squamous (ns)-NSCLC treated with bevacizumab in combination with chemotherapy. Patients receive cisplatin (80 mg/m2 i.v. d1), gemcitabine (1250 mg/m2 i.v. d1 and 8) and bevacizumab (B, 7.5 mg/kg i.v. d1) up to 6 cycles each 21 days. Pts with non-progressive disease are allowed to continue with B maintenance until PD or unacceptable toxicity. pCT assessment is done basal (d-1), at d+7 and d+42. The primary endpoint is to evaluate whether early reductions (d-1 vs d+7) in pCT parameters in terms of BF (mL/100mL/min), BV (mL/100mL) and PMB (mL/100mL/min) may predict response to bevacizumab as compared to Objective Response Rate (ORR) in terms of RECIST after 2 cycles (d+42). All perfusion evaluation parameters during treatment are measured in the same single thoracic target lesion. Planned sample size is 20 pts.

      A total of 12 pts with ns-NSCLC have been recruited and data is available for analysis in 8 pts. Mean age is 62 years, 7 males and 1 female. All pts were diagnosed of adenocarcinoma stage IV (63% stage IVb). All tumor samples were negative for EGFR/ALK and 50% positive for KRAS. Mean cycles of chemotherapy were 5 (range 2-6) and 3 (range 0-12) of B maintenance. Target lesions for perfusion were: lung 3 pts (38%), lymph nodes in 4 pts (50%) and pleura in 1 pt (12%). No differences were found in terms of basal BF, BV and PMB depending on perfusion-target chosen. Four pts (50%) achieved partial response (PR), 3 pts (38%) stable disease (SD) and 1 pt (12%) progressive disease (PD). Mean basal perfusion parameters were: BF 61,5 (34,4 - 109), BV 10,4 (3,7 - 22,2) and PMB 17 (5,5 - 27,9). Mean perfusion changes early assessed by pCT at d+7 were: BF 21,7%, BV -49% and PMB -34,4%, decreasing consistently at day +42 (BF -46,8%, BV -45,5% and PMB -53,9%). Mean early variation (d-1 vs d+7) of BF in pts with SD/PD was +1,7% as compared with -45,3% in pts with PR. Mean variation of BF compared with d+42 (d-1 vs d+42) was also greater in pts with PR (-50%). Similar trends were observed in BV and PMB.

      Early response to B as assessed with p-CT may help to select those pts with NSCLC who most benefit from antiangiogenic therapy. Early changes in perfusion parameters can be identified with B treatment. Recruitment is ongoing.

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