GOG-0218
Incorporation of bevacizumab in the primary treatment of ovarian cancer
Phase 3N = 1,873NCT00262847
- Population
- Women with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian, fallopian tube or primary peritoneal cancer after debulking surgery
- Design
- Double-blind, placebo-controlled phase 3 trial. 1873 women with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery were randomly assigned 1:1:1 to six 21-day cycles of carboplatin (AUC 6) and paclitaxel 175 mg/m2 plus placebo in cycles 2 to 22, bevacizumab 15 mg/kg in cycles 2 to 6 (initiation), or bevacizumab 15 mg/kg in cycles 2 to 22 (throughout). Primary end point progression-free survival. The final protocol-specified overall survival analysis (JCO 2019) was by intention to treat with median follow-up 102.9 months.
- Primary endpoint
- PFS
- Arms
- Chemotherapy plus placebo (control, n = 625): Carboplatin AUC 6 and paclitaxel 175 mg/m2 cycles 1 to 6, placebo cycles 2 to 22
- Chemotherapy plus bevacizumab (initiation) (experimental, n = 625): Carboplatin AUC 6 and paclitaxel 175 mg/m2 cycles 1 to 6, bevacizumab 15 mg/kg cycles 2 to 6, placebo cycles 7 to 22
- Chemotherapy plus bevacizumab (throughout) (experimental, n = 623): Carboplatin AUC 6 and paclitaxel 175 mg/m2 cycles 1 to 6, bevacizumab 15 mg/kg cycles 2 to 22
- People
- Burger RA, Gynecologic Oncology Group
PFSHR 0.717 (95% CI 0.625–0.824)Δ median PFS+3.8 monthsPFSHR 0.908 (95% CI 0.795–1.040)Δ median PFS+0.9 monthsOSHR 1.06 (95% CI 0.94–1.20)OSHR 0.96 (95% CI 0.85–1.09)
Show the numbers
| Endpoint | Analysis | Chemotherapy plus bevacizumab (initiation) / Chemotherapy plus bevacizumab (throughout) | Chemotherapy plus placebo | Effect |
|---|---|---|---|---|
| PFSRandomised women (N=1873); analysis population not stated in the abstract | primaryBurger 2011 | median 14.1 months | median 10.3 months | HR 0.717 (95% CI 0.625–0.824)P<0.001 |
| PFSRandomised women (N=1873); analysis population not stated in the abstract | primaryBurger 2011 | median 11.2 months | median 10.3 months | HR 0.908 (95% CI 0.795–1.040)P=0.16 |
| OS | finalmedian follow-up 102.9 monthsTewari 2019 | — | — | HR 1.06 (95% CI 0.94–1.20)Bevacizumab-concurrent corresponds to the initiation arm (cycles 2 to 6). No arm medians for the whole population are given in the abstract. |
| OS | finalmedian follow-up 102.9 monthsTewari 2019 | — | — | HR 0.96 (95% CI 0.85–1.09)Bevacizumab-concurrent plus maintenance corresponds to the throughout arm (cycles 2 to 22). The abstract states that no survival advantage was observed after censoring patients who received bevacizumab at crossover or as second line. |
| OSStage IV disease (subgroup) | exploratorymedian follow-up 102.9 monthsTewari 2019 | median 42.8 months | median 32.6 months | HR 0.75 (95% CI 0.59–0.95)Subgroup analysis; the abstract does not say whether it was prespecified. It sits beside an overall HR of 0.96, so it is not an overall survival benefit. |
| Endpoint | Analysis | Chemotherapy plus bevacizumab (initiation) / Chemotherapy plus bevacizumab (throughout) | Chemotherapy plus placebo | Effect |
|---|---|---|---|---|
| PFSRandomised women (N=1873); analysis population not stated in the abstract | primaryBurger 2011 | median 14.1 months | median 10.3 months | HR 0.717 (95% CI 0.625–0.824)P<0.001 |
| PFSRandomised women (N=1873); analysis population not stated in the abstract | primaryBurger 2011 | median 11.2 months | median 10.3 months | HR 0.908 (95% CI 0.795–1.040)P=0.16 |
| OS | finalmedian follow-up 102.9 monthsTewari 2019 | — | — | HR 1.06 (95% CI 0.94–1.20)Bevacizumab-concurrent corresponds to the initiation arm (cycles 2 to 6). No arm medians for the whole population are given in the abstract. |
| OS | finalmedian follow-up 102.9 monthsTewari 2019 | — | — | HR 0.96 (95% CI 0.85–1.09)Bevacizumab-concurrent plus maintenance corresponds to the throughout arm (cycles 2 to 22). The abstract states that no survival advantage was observed after censoring patients who received bevacizumab at crossover or as second line. |
| OSStage IV disease (subgroup) | exploratorymedian follow-up 102.9 monthsTewari 2019 | median 42.8 months | median 32.6 months | HR 0.75 (95% CI 0.59–0.95)Subgroup analysis; the abstract does not say whether it was prespecified. It sits beside an overall HR of 0.96, so it is not an overall survival benefit. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.717 | 0.625–0.824 |
| PFS | 0.908 | 0.795–1.04 |
| OS | 1.06 | 0.94–1.2 |
| OS | 0.96 | 0.85–1.09 |
| OS | 0.75 | 0.59–0.95 |
- Chemotherapy plus bevacizumab (throughout) (experimental)
- Chemotherapy plus placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chemotherapy plus bevacizumab (throughout) | Chemotherapy plus placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 9 | 64.2% | 54.6% |
| 18 | 41.3% | 29.8% |
| 26 | 27.9% | 17.4% |
| 35 | 17.9% | 9.5% |
- Chemotherapy plus bevacizumab (initiation) (experimental)
- Chemotherapy plus placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Chemotherapy plus bevacizumab (initiation) | Chemotherapy plus placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 64.8% | 62.4% |
| 14 | 42.0% | 39.0% |
| 21 | 27.3% | 24.3% |
| 28 | 17.7% | 15.2% |
Appears in
Sources
Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-83.
Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019;37(26):2317-2328.