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J. Polikoff
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-057 - Randomized Phase 2 Study of Plinabulin and Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer - Mechanism-Based Efficacy Analyses (ID 1505)
09:30 - 09:30 | Author(s): J. Polikoff
- Abstract
Background:
Plinabulin (N), a tubulin binding agent, which depolarizes microtubules, resulting in tumor vasculature obliteration, apoptosis via JNK pathway and maturation of dendritic cells. A multicenter randomized phase 2 study was performed to compare overall survival (OS) between plinabulin/docetaxel (DN) and docetaxel (D). Results of Intent-to-treat (ITT) analyses have been presented at ASCO 2014. The primary objective of OS prolongation was not met, however, exploratory mechanism based analysis revealed improvement in outcomes in patients with large tumors.
Methods:
From November 2008 to July 2011 172 patients with advanced NSCLC who progressed after at least one chemotherapy were enrolled. Patients were treated with D 75mg/m[2] on day 1 and N 30 mg/[2] on days 1 and 8. A second cohort of N 20 mg/m[2] was also enrolled. This exploratory analysis is based on 105 patients (50 DN arm and 55 D arm) receiving 30 mg/m[2] dose, which was selected for an ongoing Phase 3 study and explains the population chosen for future investigation.
Results:
Median OS was 8.7 months (m) (CI 6.6-12.6) in DN arm and 7.5 m (6.3-10.5) in D arm (p=0.899, HR=0.97). PFS was 2.8 m and 3.5 m and ORR was 14.0% vs 14.5% respectively. Among clinical parameters, lesion size (Table 1) and presence of pulmonary disease were identified to impact OS. The OS in patients with pulmonary disease was 11.3 m (6.7-15.1) in DN and 6.7 m (6-9.8) in D, respectively (p=0.29, HR=0.76) regardless of lesion size. Table 1: Exploratory Analysis of Overall Survival by Tumor Size
CI = confidence interval; D = docetaxel; DN, docetaxel + plinabulin; ITT = intent-to-treat; OS = overall survival (Months).Patients Tumor size Median OS Months (95% CI) Hazard Ratio P-value DN (30mg/m[2]) D ITT 1 and 2 prior chemo-therapy All 8.68 (6.33, 12.63) N=50 7.47 (6.17, 10.60) N=55 0.972 0.8993 ≤ 3 cm 6.45 (3.73, NA) N=16 6.47 (5.6, 22.43) N=19 0.934 0.8687 > 3 cm 8.98 (6.60, 12.63) N=34 7.47 (4.77, 11.60) N=36 0.967 0.8990 > 5 cm 8.98 (4.57, 19.23) N= 20 6.70 (4.07, 12.93) N=21 0.750 0.4176 > 7 cm 7.32 (4.57, 19.23) N= 8 5.03 (2.93, 6.70) N= 10 0.507 0.1936
Conclusion:
Mechanism-based exploratory analyses of Phase 2 results have identified advanced NSCLC patients with lung lesion size >3 cm to have benefited from plinabulin. A Phase 3 to confirm this observation is on-going.
