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N. Vogelzang
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P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.09-011 - LUME-Meso Phase II/III Study: Nintedanib + Pemetrexed/Cisplatin in Chemo-Naïve Patients with Malignant Pleural Mesothelioma (ID 7937)
09:30 - 09:30 | Author(s): N. Vogelzang
- Abstract
Background:
Pemetrexed/cisplatin is the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM), with median overall survival (OS) of ~1 year. Nintedanib is a triple angiokinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3, platelet-derived growth factor (PDGF) receptors α/β and fibroblast growth factor receptors 1–3. VEGF and PDGF overexpression are associated with poor prognosis in MPM, and nintedanib has demonstrated efficacy in preclinical MPM models. Nintedanib also targets the Src and Abl kinases, which are involved in MPM cell migration. A randomised Phase II trial of nintedanib or placebo + pemetrexed/cisplatin in MPM followed by maintenance nintedanib or placebo, with progression-free survival (PFS) as the primary endpoint, was performed. With regulatory authority guidance, the Phase II data were unblinded. At the primary analysis, PFS benefit was observed with nintedanib, and confirmed at the updated analysis (hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.33–0.87; p=0.010; median PFS: nintedanib 9.4 months vs placebo 5.7 months). A strong signal towards improved OS also favoured nintedanib (HR=0.77, 95% CI: 0.46–1.29; p=0.319; median OS: 18.3 vs 14.2 months). The study was expanded to include a confirmatory Phase III part based on the primary PFS results, and the Phase II data assisted in planning of the Phase III part, including sample size estimation. Nintedanib was granted US Food and Drug Administration orphan drug designation for the treatment of MPM in December 2016.
Method:
The Phase III part of the study (NCT01907100) is currently recruiting participants. Four hundred and fifty chemotherapy-naïve patients worldwide (~140 sites in 27 countries), aged ≥18 years with unresectable MPM of epithelioid histology and Eastern Cooperative Oncology Group performance score 0–1 will be randomised 1:1 to receive up to six 21-day cycles of pemetrexed (500 mg/m[2])/cisplatin (75 mg/m[2]) on Day 1 + nintedanib or placebo (200 mg twice daily, Days 2–21), followed by nintedanib or placebo monotherapy until disease progression or undue toxicity. The primary endpoint is PFS with the key secondary endpoint being OS. An adaptive design will be used at the time of the primary PFS analysis to reassess the number of OS events for sufficient OS power. Other secondary endpoints are objective response and disease control (using modified Response Evaluation Criteria in Solid Tumors). The frequency and severity of adverse events, as well as health-related quality of life, will also be assessed. An exploratory analysis of predictive/prognostic biomarkers is planned.
Result:
Section not applicable
Conclusion:
Section not applicable
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-001 - Effects of Tumor Burden Reduction on Survival in Epithelioid Pleural Mesothelioma (ID 7518)
09:30 - 09:30 | Author(s): N. Vogelzang
- Abstract
Background:
Surrogate endpoints are commonly utilized in oncology clinical trials and have been adopted by regulatory agencies for the approval of many agents. To date, the effects of tumor size reduction on survival have not been determined for the only Food and Drug Administration (FDA)-approved regimen fo malignant pleural mesothelioma (MPM), but its widespread use mandates its validation. MPM is a challenging disease to assess and standard Response Evaluation Criteria for Solid Tumors (RECIST) were not optimized to measure pleural disease. Modified pleural RECIST (mRECIST) have been adopted by mesothelioma experts for the measurement of responses in MPM and mRECIST are the most commonly used response criteria in clinical trials for MPM. Although the gold standards for oncology outcomes are overall survival and quality of life, cross-over to subsequent therapies and competing risks influence survival outcomes. We sought to evaluate the relationship of response with survival in the clinical trial of the only FDA approved regimen for MPM.
Method:
We reviewed the clinical trial that randomized patients with MPM to receive cisplatin or cisplatin and pemetrexed. Patients with epithelioid MPM were categorized by whether or not they responded to cisplatin or the combination of cisplatin and pemetrexed accoring to the original study determination. Responders had >30% reduction in the thickness of the pleural rind measured at up to 3 points on 3 separate slices of the CT scan. Median progression-free (PFS) and overall survivals (OS) were determined and the hazard ratios for responders and non-responders were determined and compared by the logrank test.
Result:
We identified that patients with epithelioid MPM who responded to front-line therapy had a significantly longer overall survival (HR 0.341, 95% CI 0.239-0.486; median 20.6 months, 95% CI: 15.3-not reached) than those who did not respond (median 9.4 months, 95% CI: 8.1-11.0; p<0.001). Similarly patients who responded to front-line therapy had a significantly longer progression-free survival (HR 0.496, 95% CI: 0.385-0.639; median 7.8 months, 95% CI: 6.5-8.5) than those who did not respond (median 3.7 months, 95% CI: 2.9-4.3; p<0.001).
Conclusion:
Our findings demonstrate that a reduction in tumor burden was strongly associated with OS and PFS in epithelioid MPM treated with cisplatin or cisplatin and pemetrexed.
