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H. Roder



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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.01 - Randomized Proteomic Stratified Phase III Study of Second Line Erlotinib (E) versus Chemotherapy (CT) in Patients with Inoperable Non-Small Cell Lung Cancer (PROSE): VeriStrat analysis of longitudinal samples (ID 3122)

      10:30 - 12:00  |  Author(s): H. Roder

      • Abstract
      • Presentation
      • Slides

      Background
      2nd-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. A test for optimizing choice of treatment in these pts is of clinical value. VeriStrat (VS) is a serum protein test that assigns "good" (VSG) or "poor" (VSP) classification and has demonstrated prognostic and predictive utility. PROSE is a multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in 2nd- line NSCLC pts treated with E or CT. As reported at 2013 ASCO1, PROSE met its primary endpoint of demonstrating significant treatment*VS interaction with a p value of 0.031, with VSG pts deriving similar overall survival (OS) benefit from both treatments (hazard ratio (HR) for E=1.06; p=0.71) and VSP pts benefitting more from CT than E (HR for E=1.72; p=0.02). Previous studies in EGFR-TKI-treated pts have shown that at progression around 30% of pre-treatment VSG pts have changed classification to VSP2. The present report discusses the exploratory analysis of longitudinal VS classifications generated during the PROSE study.

      Methods
      Of the 263 pts in the PROSE primary analysis population, 89 provided serum samples during treatment and 108 at progression, with 47 pts providing both. VS testing was performed on these longitudinal samples blinded to all clinical and treatment outcomes and pts and physicians remained blinded to VS results.

      Results
      VSG or VSP classifications were obtained for 89 pts from treatment samples (67 VSG / 22 VSP) and 107 pts (one sample was classified as indeterminate) from progression samples (59 VSG / 48 VSP). In pts with matched baseline and progression samples, the percentage of VSG classifications was lower at progression (55%) than at baseline (77%) (p < 0.001 ). Twenty eight pts (34%) classified at baseline as VSG changed to VSP at progression, in line with previous studies2, and this did not show any significant dependence on treatment. When treated with E, pts whose classification changed from VSG at baseline to VSP during treatment (n=6) had inferior PFS to the 25 pts who remained VSG (p=0.001, median PFS: 3.6 and 7.7 months (mos), respectively). Patients whose classification changed from VSG at baseline to VSP at progression on E (n=18) had numerically inferior OS (median 10.0 mos) compared with the 31 pts who remained VSG at progression (median 14.6 mos) and significantly superior OS (median 5.0 mos) compared with the 10 pts who were VSP at both time points (p<0.001).

      Conclusion
      The observed changes in VS classification at progression demonstrate the importance of obtaining a VS result prior to each line of therapy for which erlotinib is considered as a therapeutic option. The proportion of patients who are good candidates for erlotinib therapy (VSG) decreases from 2[nd] to 3[rd] line and the possible impact of this on treatment sequencing and monitoring for 2[nd] and higher line advanced NSCLC pts merits further studies.

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    O01 - Prognostic and Predictive Biomarkers I (ID 94)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O01.07 - Randomized Proteomic Stratified Phase III Study of Second Line Erlotinib (E) versus Chemotherapy (CT) in Patients with Inoperable Non-Small Cell Lung Cancer (PROSE): Secondary Endpoint Analysis (ID 3276)

      10:30 - 12:00  |  Author(s): H. Roder

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR-TKis are more effective in NSCLC patients with EGFR activating mutations. However, about 90% of non-Asian patients are EGFR wild type, and a test for optimizing treatment in pts with wild-type or in patients with undetectable EGFR mutation status or squamous histology is of clinical value. VeriStrat (VS) is a serum protein test that assigns "good" (VSG) or "poor" (VSP) classification and has demonstrated prognostic and predictive utility in retrospective studies. PROSE is the first completed multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in 2[nd]- line NSCLC pts treated with E or CT. As reported at 2013 ASCO[1], VSG pts derived similar overall survival (OS) benefit from both agents (hazard ratio (HR) for E=1.06; p=0.71) whereas CT was the superior option for VSP pts (HR for E=1.72; p=0.02). PROSE met its primary endpoint of demonstrating significant treatment*VS interaction with a p-value of 0.031. The present report discusses the results for the secondary endpoints, PFS.

      Methods
      285 pts, stratified by ECOG-PS, smoking, and blinded pre-treatment VS classification, were randomized 1:1 to receive E or CT at standard doses. Primary endpoint was overall survival (OS) and the primary hypothesis was a significant interaction between VS status and treatment. Sample size was calculated based on an estimated 65%/35% VSG:VSP ratio and hazard ratio (HR) for interaction of 2.35, with a 2-sided α=0.05 and 90% power.

      Results
      263 pts (129 CT, 134 E) were included in the per protocol primary analysis. 68% of pts in CT arm and 72% in E arm were classified as VSG, and analysis was performed at 226 survival events.VSP classification was significantly correlated with worse PFS as compared to VSG, in overall comparison (HR=1.75, 95%CI: 1.34-2.95, P <0.001) , in the CT (HR = 1.69, 95%CI: 1.15-2.48, P <0.007) and the E (HR = 1.91, 95%CI: 1.340-2.80, P<0.001) arms, demonstrating its prognostic value also in PFS. In VSG median PFS was 4.8 months (m) on CT, and 2.5 m on E (HR = 1.26, 95% CI: 0.94-1.69, P =0.129); in VSP median PFS was 2.8 m on CT and 1.7 m on E (HR=1.51, 95% CI: 0.96-2.38, P =0.078). No statistical significant interaction was detected (p=0.44)

      Conclusion
      The analysis of PFS and OS indicates that the differential treatment benefit in OS related to VS classification is determined by the combination of prognostic and predictive properties of the test.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-036 - Prospective correlative study of FDG-PET SUV and proteomic profile (VeriStrat) of Non Small Cell Lung Cancer (NSCLC) patients treated with erlotinib (ID 2693)

      09:30 - 16:30  |  Author(s): H. Roder

      • Abstract

      Background
      VeriStrat (VS) is a multivariate protein serum test that classifies Non Small Cell Lung Cancer (NSCLC) patients in 2 categories VS Good or VS Poor according to the overall survival (OS) of patients treated with EGFR-TKIs. Recently, the prospective Phase III PROSE study showed that the VS algorithm is predictive of differential OS benefit for erlotinib (E) vs second line standard chemotherapy (CT): VS Poor classified patients had worse OS on E compared to CT, while there was no significant difference between treatments outcome in the VSG group. Aim of the current study was to evaluate if baseline Standardized Uptake Value (SUV) of FDG-PET may help to optimize treatment choice between E or CT IN VS Good classified pts.

      Methods
      Plasma samples were collected before the beginning of E from metastatic NSCLC patients. Acquired spectra were classified according to the VS algorithm. The FDG-PET was performed tha day before the beginning of E. Survival curves were estimated using the Kaplan-Meier method.

      Results
      Thirty eight NSCLC patients on E therapy with the following characteristics were analyzed: median age 62 years old, 63% were males, 53% had adenocarcinoma histology, response rate was 26%, median OS 10 mos and TTP 3.4 mos. Twenty-six (68%) were classified as VS Good, 12 (32%) as Poor. TTP and OS for VS Good and Poor were 4.1 vs 2.1 mos (HR 0.86, log-rank p=0.6) and 11.1 vs 4.1 mos (HR 0.45,log-rank p=0.02), respectively. All VS Poor classified patients had SUV ≥ 7 and had the worst TTP and OS; VS Good classified patients with baseline SUV level ≥ 7 had worse OS (10 mos) and worse TTP (2.1 mos) compared to those who were VS Good and had SUV<7 (OS 16 mos) (TTP 13.8 mos).

      Conclusion
      The study confirmed that VS Poor classified patients had significantly shorter OS than those classified as VS Good. Patients with VS Good profile and with baseline FDG-PET SUVs levels <7 may benefit more from EGFR-TKIs than VS Good patients with higher FDG-PET SUV, suggesting that FDG-PET analysis may be a clinically useful tool for EGFR-TKIs therapy selection.