JGOG 3016
Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial
Phase 3N = 637NCT00226915
- Population
- Patients with stage II-IV epithelial ovarian, fallopian tube or primary peritoneal cancer treated at 85 centres in Japan
- Design
- Phase 3, open-label randomised trial at 85 centres in Japan. Patients with stage II to IV epithelial ovarian, fallopian tube or primary peritoneal cancer were randomly assigned to six cycles of paclitaxel 180 mg/m2 (3-hour infusion) plus carboplatin AUC 6 on day 1 of a 21-day cycle (conventional, n=320), or paclitaxel 80 mg/m2 (1-hour infusion) on days 1, 8 and 15 plus carboplatin on day 1 (dose-dense, n=317). 637 patients were enrolled and 631 were included in the ITT population (dose-dense 312, conventional 319). Primary endpoint progression-free survival. Median follow-up in the long-term report was 76.8 months.
- Primary endpoint
- PFS
- Arms
- Conventional paclitaxel and carboplatin (control, n = 320): Paclitaxel 180 mg/m2 over 3 hours plus carboplatin AUC 6 on day 1 of a 21-day cycle, six cycles
- Dose-dense weekly paclitaxel and carboplatin (experimental, n = 317): Paclitaxel 80 mg/m2 over 1 hour on days 1, 8 and 15 plus carboplatin AUC 6 on day 1 of a 21-day cycle, six cycles
- People
- Katsumata N, Japanese Gynecologic Oncology Group
PFSHR 0.71 (95% CI 0.58–0.88)Δ median PFS+10.8 monthsOSHR 0.75 (95% CI 0.57–0.98)Δ 36-month OS+7 pointsPFSHR 0.76 (95% CI 0.62–0.91)Δ median PFS+10.7 months
Show the numbers
| Endpoint | Analysis | Dose-dense weekly paclitaxel and carboplatin | Conventional paclitaxel and carboplatin | Effect |
|---|---|---|---|---|
| PFS | primaryKatsumata 2009 | median 28 months (22.3–35.4) | median 17.2 months (15.7–21.1) | HR 0.71 (95% CI 0.58–0.88)P=0.0015 |
| OS | primaryKatsumata 2009 | 72.1% at 3 y | 65.1% at 3 y | HR 0.75 (95% CI 0.57–0.98)P=0.03Overall survival at 3 years is a landmark proportion; at the primary report it was not the primary endpoint. |
| PFS | long term-updatemedian follow-up 76.8 monthsKatsumata 2013 | median 28.2 months (22.3–33.8) | median 17.5 months (15.7–21.7) | HR 0.76 (95% CI 0.62–0.91)P=0.0037 |
| OS | long term-updatemedian follow-up 76.8 monthsKatsumata 2013 | median 100.5 months | median 62.2 months (52.1–82.6) | HR 0.79 (95% CI 0.63–0.99)P=0.039The abstract gives the dose-dense median OS 95% CI as 65.2 months to infinity; an interval with an infinite upper bound cannot be entered, so the dose-dense median is recorded without its CI. Overall survival was a secondary endpoint. |
| Endpoint | Analysis | Dose-dense weekly paclitaxel and carboplatin | Conventional paclitaxel and carboplatin | Effect |
|---|---|---|---|---|
| PFS | primaryKatsumata 2009 | median 28 months (22.3–35.4) | median 17.2 months (15.7–21.1) | HR 0.71 (95% CI 0.58–0.88)P=0.0015 |
| OS | primaryKatsumata 2009 | 72.1% at 3 y | 65.1% at 3 y | HR 0.75 (95% CI 0.57–0.98)P=0.03Overall survival at 3 years is a landmark proportion; at the primary report it was not the primary endpoint. |
| PFS | long term-updatemedian follow-up 76.8 monthsKatsumata 2013 | median 28.2 months (22.3–33.8) | median 17.5 months (15.7–21.7) | HR 0.76 (95% CI 0.62–0.91)P=0.0037 |
| OS | long term-updatemedian follow-up 76.8 monthsKatsumata 2013 | median 100.5 months | median 62.2 months (52.1–82.6) | HR 0.79 (95% CI 0.63–0.99)P=0.039The abstract gives the dose-dense median OS 95% CI as 65.2 months to infinity; an interval with an infinite upper bound cannot be entered, so the dose-dense median is recorded without its CI. Overall survival was a secondary endpoint. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.71 | 0.58–0.88 |
| OS | 0.75 | 0.57–0.98 |
| PFS | 0.76 | 0.62–0.91 |
| OS | 0.79 | 0.63–0.99 |
- Dose-dense weekly paclitaxel and carboplatin (experimental)
- Conventional paclitaxel and carboplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Dose-dense weekly paclitaxel and carboplatin | Conventional paclitaxel and carboplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 18 | 64.0% | 48.4% |
| 35 | 42.0% | 24.4% |
| 53 | 26.9% | 11.8% |
| 70 | 17.7% | 6.0% |
- Dose-dense weekly paclitaxel and carboplatin (experimental)
- Conventional paclitaxel and carboplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Dose-dense weekly paclitaxel and carboplatin | Conventional paclitaxel and carboplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 18 | 64.2% | 49.0% |
| 35 | 42.3% | 25.0% |
| 53 | 27.2% | 12.3% |
| 71 | 17.5% | 6.0% |
Appears in
Sources
Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374(9698):1331-8.
Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, et al. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol. 2013;14(10):1020-6.