Phase III Trial of Induction Gemcitabine (G) or Paclitaxel (T) Plus Carboplatin (C) Followed by Elective T Consolidation in Ovarian Cancer (OC), Stages IC to IV: Final Safety and Efficacy Report M. Teneriello 1 , A. Gordon 2 , P. Lim 3 , M. Janicek 4 1 US Oncology, Houston, TX and Texas Oncology, Austin, TX 2 MD Anderson Cancer Center Orlando, Orlando, FL 3 Center of Hope at Renown Regional Medical Center, Reno, NV 4 OncoGyne, Scottsdale, AZ
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Phase III Trial of Induction Gemcitabine (G) or Paclitaxel (T) Plus Carboplatin (C) Followed by Elective T Consolidation in Ovarian Cancer (OC), Stages.
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Phase III Trial of Induction Gemcitabine (G) or Paclitaxel (T) Plus Carboplatin (C) Followed by
Elective T Consolidation in Ovarian Cancer (OC), Stages IC to IV: Final Safety and Efficacy Report
M. Teneriello1, A. Gordon2, P. Lim3, M. Janicek4
1 US Oncology, Houston, TX and Texas Oncology, Austin, TX2 MD Anderson Cancer Center Orlando, Orlando, FL3 Center of Hope at Renown Regional Medical Center, Reno, NV4 OncoGyne, Scottsdale, AZ
Disclosure Information
The authors have no conflicts of interest to report.
This study was sponsored by Eli Lilly and Company.
Background
• Induction chemotherapy with a platinum agent and paclitaxel (T) is a standard of care for Stage IC-IV ovarian cancer (OC).
• Combination gemcitabine and carboplatin (GC) is approved for use in recurrent platinum-sensitive OC.
• Phase II trials have previously shown the combination of G plus cisplatin to be active as first-line therapy for OC.1-3
• Evidence suggests (SWOG 9701/GOG 178) that 12‑month T consolidation (Tcon) improves progression-free survival (PFS).4
• The current study was designed to compare GC to standard first-line therapy, followed by Tcon.
1 Belpomme D, et al. Gynecol Oncol 2003.2 Nogué M, et al. Anticancer Drugs 2002.3 Bauknecht T, et al. Int J Gynecol Cancer 2003.4 Markman M, et al. J Clin Oncol 2003.
Background
• The study was initiated in October 2002 as a multi- center, open-label, dual-arm, randomized, Phase III, superiority trial.
• In June 2004, Tcon was changed from mandatory to elective after 362 patients had been enrolled.
• Planned enrollment was 1208 patients. In August 2006, the protocol was modified to allow PFS as primary endpoint. Subsequently, enrollment was stopped at 919 patients, an adequate sample size for estimation of PFS.
• The trial was stopped in October 2009 after an ad hoc futility analysis showed low probability of a positive PFS result.
Objectives
Primary Objective
• To compare PFS in the experimental arm (GC) to the control arm, paclitaxel and carboplatin (TC)
Secondary Objectives
• To compare efficacy of the two regimens with respect to response rate and OS
• To compare adverse events related to each regimen
* Cox regression analysis was performed using baseline patient characteristics: performance status, tumor size after debulking, FIGO stage, and histology.
Summary
• In 2006 the protocol was modified to allow PFS as primary endpoint and enrollment was stopped at 919 patients.
• Demographics were well balanced between arms.
• Toxicity profiles were consistent with prior clinical experience.
• Response results were not statistically different comparing the two induction or crossover arms.
Summary
• For PFS, the primary endpoint, there was no difference for induction, consolidation, and crossover groups.
• Adjusting for significant covariates, there was no significant difference in OS between the two arms.
• Subset analysis suggested that OS may be improved for patients receiving Tcon after achieving CR.
• The OS analysis was severely limited by: early study closure, the high rate of censored data, unrecoverable data, and non-randomization for the consolidation treatment.
Conclusions
• GC did not offer an advantage over standard of care TC for first-line chemotherapy in OC.
• Paclitaxel consolidation may have improved OS, but analysis was limited by study design and high censorship.
• The utility of paclitaxel consolidation cannot be answered by this trial.
We thank...
• The 85 trial Investigators at 63 sites in the United States.
• The Lilly Medical team.
• Our patients.
Acknowledgements
Phase III Trial of Induction Gemcitabine (G) or Paclitaxel (T) Plus Carboplatin (C) Followed by
Elective T Consolidation in Ovarian Cancer (OC), Stages IC to IV: Final Safety and Efficacy Report
M. Teneriello1, A. Gordon2, P. Lim3, M. Janicek4
1 US Oncology, Houston, TX and Texas Oncology, Austin, TX2 MD Anderson Cancer Center Orlando, Orlando, FL3 Center of Hope at Renown Regional Medical Center, Reno, NV4 OncoGyne, Scottsdale, AZ
Discussion Slides
Drug Administration
ParameterGC
N=412TC
N=408
Tcon-G
N=169
Tcon-TN=183
CO-GN=78
CO-TN=77
Total cycles administered, n 2221 2194 1583 1760 417 513
Mean cycles administered, n 5.4 5.4 9.4 9.6 5.3 6.7
Median cycles administered, n 6 6 12 12 5 6
Cycles with dose reduction, n/(%)312
(14.0)107(4.9)
23(1.4)
40(2.3)
32(7.7)
25(4.9)
Abbreviations: Tcon-G, paclitaxel consolidation after GC; Tcon-T, paclitaxel consolidation after TC.