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E. Rijavec



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    MA 01 - SCLC: Research Perspectives (ID 650)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA 01.07 - Lanreotide Maintenance in SCLC Expressing Somatostatine Receptors: Efficacy Results of Multicenter Randomized G04.2011 Trial (ID 8480)

      11:00 - 12:30  |  Author(s): E. Rijavec

      • Abstract
      • Presentation
      • Slides

      Background:
      SCLC is featured by both a rapid response and progression during/after standard upfront therapy. Thus, maintenance strategies emerged as potential treatment opportunities, although to date all drugs failed to significantly improve prognosis. SCLC cells harbor a neuroendocrine phenotype, frequently expressing somatostatine (SST) receptors. This study aimed to investigate the efficacy of somatostatine (SST) analogue Lanreotide (LAN) as a maintenance strategy for SCLC patients (pts) after response to standard upfront treatment.

      Method:
      A multicentre, randomized, open-label, no-profit national trial was conducted, randomizing (1:1) SCLC (limited/extended disease, L/ED) pts expressing SST receptors (by SST receptor scintigraphy) with objective response (CR or PR) after upfront platinum-based chemotherapy plus/minus radiotherapy to receive maintenance LAN 120 mg subcutaneously every 28 days, up to progressive disease (PD) for 1 year (Arm A), versus observation (Arm B). Primary end-point was 1-year Progression-Free Survival (PFS). Primary intention-to-treat (ITT) analysis was planned (power: 80%; 2-tailed alpha-error: 5%) after 47 PFS events.

      Result:
      Seventy-one pts (median age 66 [37-82]; male/female 72/28%; L/ED 39/61%; ECOG-PS 0-1/2 97/3%; previous best response CR/PR 6/94%) were randomized in 9 Italian centers. Median time from diagnosis and end-of-1[st] line to inclusion was 5.7 months (3-160) and 30 days (0-119), respectively. Median number of LAN doses and treatment duration (Arm A) was 4 (1-12) and 83 days (1-392), respectively. With a median follow-up of 9.4 months and 62 events, median PFS was 3.6 (95% CI 3.2-3.9) versus 2.3 months (95% CI 1.7-2.9), for Arm A and B (log-rank p=0.11; HR 1.51, 95% CI 0.90-2.50), with a 1-year PFS of 10.3% versus 7.3%, respectively. At the cox-proportional multivariate modelling, stage (ED versus LD, HR 2.88 [95% CI 1.64-5.04, p<0.0001) and treatment arm (B versus A, HR 1.63 [95% CI 0.97-2.72], p=0.06) were independent predictors for PFS. Median PFS of arm A and B was 7.0 [95% CI <1-13.5] and 3.8 months [95% CI <1-8.6] in LD pts (p=0.21), and 3.0 (95% CI 2.2-3.8) and 2.2 (95% 1.7-2.7) in ED pts (p=0.19). Median OS was 9.5 (95% CI 4.8-14.3) and 4.7 months (95% CI 1.7-16.6), for Arm A and B (log-rank p=0.47), respectively. LAN was well-tolerated: serious treatment-related adverse events were grade 3 abdominal pain and electrolyte disorder in overall 2 pts.

      Conclusion:
      Although the primary end-point was not met, the overall efficacy of LAN as a maintenance strategy after response to standard upfront treatment for SCLC deserves future investigations, particularly in pts with LD.

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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-023 - The Correlation Between B7-H4 Expression and Survival of Non-Small Cell Lung Cancer Patients Treated with Nivolumab (ID 9569)

      09:30 - 16:00  |  Author(s): E. Rijavec

      • Abstract

      Background:
      In spite of the results achieved by nivolumab in advanced non-small cell lung cancer (NSCLC), reliable predictive factors are still needed, and even the expression of the programmed death protein 1 ligand (PD-L1) has a limited role in predicting benefit from this agent. Our aim was to determine whether the expression of other molecules involved in immune response might be associated with outcomes of NSCLC patients receiving nivolumab.

      Method:
      This retrospective study included patients treated with nivolumab for advanced NSCLC (Nivolumab Cohort). Response rate (RR) and progression-free survival (PFS) were assessed by response evaluation criteria in solid tumors (RECIST) v 1.1 and immune-related response criteria (irRC). Available tumor specimens were analyzed by immunohistochemistry (IHC) in order to determine the expression of PD-L1, PD-1 ligand 2 (PD-L2), PD-1, B7-H3, and B7-H4. The possible correlations between IHC findings and clinical outcomes were explored. Additionally, the meaningful biomarkers observed in the Nivolumab Cohort were assessed in a population of NSCLC patients treated with platinum-based chemotherapy (Chemotherapy Cohort) and the results from the two cohorts were compared in order to determine whether the administered treatment played a role in our observations.

      Result:
      The Nivolumab Cohort included 46 evaluable patients. The following proportions of positive IHC samples were observed: PD-L1=15.22%; PD-L2= 17.39; PD-1= 67.39%; B7-H3= 13.04%; B7-H4= 36.96%. At univariate analysis, patients expressing B7-H4 ≥1% had significantly lower PFS compared to those patients with B7-H4 <1% according to RECIST (1.67 vs. 2.00 months; p= 0.026) and irRC (1.73 vs. 2.17 months; p= 0.039), as well as a numerically lower overall survival (OS; 4.37 vs. 9.83 months; p= 0.064). At multivariate analysis for OS, PD-L1 ≥1% had favorable effect (HR= 0.29; p= 0.027), while B7-H4 ≥1% had unfavorable effect (HR= 2.98; p= 0.006). No other correlation was observed in this cohort. Within the Chemotherapy Cohort (n=27), no significant correlation between IHC findings and response or survival was observed. At the multivariate analysis including both cohorts, a statistically significant interaction was observed between OS and the combined effect of B7-H4 expression and treatment (p= 0.048), favoring nivolumab in B7-H4 <1% patients (HR= 0.60) and chemotherapy in B7-H4 ≥1% patients (HR= 0.67).

      Conclusion:
      A meaningful negative correlation between B7-H4 expression and outcomes was observed with nivolumab, but not with chemotherapy. In spite of a relatively small patient population, our results strongly encourage further studies exploring the potential role of B7-H4 as predictor of outcomes during treatment with nivolumab.