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M. Mencoboni
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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
- Moderators:D.C. Lam, S.M. Lee
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside Auditorium A, Level 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 - 10:35 | Author(s): M. Mencoboni
- Abstract
- Presentation
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.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O01 - Prognostic and Predictive Biomarkers I (ID 94)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:T. Mitsudomi, V. Gregorc
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Auditorium, Level 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)
11:35 - 11:45 | Author(s): M. Mencoboni
- Abstract
- Presentation
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.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
