PORTEC-3
Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3)
Phase 3N = 686NCT00411138
- Population
- High-risk endometrial cancer, FIGO 2009 stage I endometrioid grade 3 with deep myometrial invasion and/or lymphovascular space invasion, stage II or III, or stage I to III with serous or clear-cell histology; WHO performance status 0-2
- Design
- Open-label, international, multicentre, randomised phase 3 trial in 103 centres (six trial groups of the Gynaecological Cancer Intergroup). Radiotherapy alone (48.6 Gy in 1.8 Gy fractions) or radiotherapy with two cycles of cisplatin 50 mg/m2 during radiotherapy followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2. Biased-coin minimisation with stratification for centre, lymphadenectomy, stage and histological type. 686 women were enrolled between 23 November 2006 and 20 December 2013; 660 eligible patients (330 per arm) were in the analyses. Co-primary endpoints overall survival and failure-free survival. ClinicalTrials.gov lists an estimated enrolment of 670.
- Primary endpoint
- OS, FFS
- Arms
- Pelvic radiotherapy alone (control, n = 330): Pelvic radiotherapy 48.6 Gy in 1.8 Gy fractions, five days per week
- Chemoradiotherapy (experimental, n = 330): Radiotherapy 48.6 Gy with two cycles of cisplatin 50 mg/m2 during radiotherapy, then four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2
- People
- de Boer SM
OSHR 0.76 (95% CI 0.54–1.06)Δ 60-month OS+5.1 pointsFFSHR 0.71 (95% CI 0.53–0.95)Δ 60-month FFS+6.9 pointsΔ Grade 3 or worse adverse events+48 pointsΔ 36-month Grade 2 or worse neuropathy+7 points
Show the numbers
| Endpoint | Analysis | Chemoradiotherapy | Pelvic radiotherapy alone | Effect |
|---|---|---|---|---|
| OS5-year overall survival; co-primary endpoint | primarymedian follow-up 60.2 monthsde 2018 | 81.8% at 5 y (77.5–86.2%) | 76.7% at 5 y (72.1–81.6%) | HR 0.76 (95% CI 0.54–1.06)P=0.11Adjusted hazard ratio (adjusted for stratification factors). 660 eligible patients were included in the final analysis (330 per arm) of 686 enrolled. |
| FFS5-year failure-free survival; co-primary endpoint | primarymedian follow-up 60.2 monthsde 2018 | 75.5% at 5 y (70.3–79.9%) | 68.6% at 5 y (63.1–73.4%) | HR 0.71 (95% CI 0.53–0.95)P=0.022Hazard ratio adjusted for stratification factors. |
| Grade 3 or worse adverse eventsPatients as reported in the treatment safety analysis (330 per arm)Grade 3 or worse adverse events during treatment | primaryde 2018 | 60% | 12% | P<0.0001198 of 330 patients with chemoradiotherapy versus 41 of 330 with radiotherapy. |
| Grade 2 or worse neuropathyWomen assessed at 3 yearsNeuropathy of grade 2 or worse persisting at 3 years | primaryde 2018 | 8% at 3 y | 1% at 3 y | P<0.000120 women (8%) versus one (1%) at 3 years. |
| OS5-year overall survival in the updated analysis with one additional year of follow-up; co-primary endpoint | long term-updatemedian follow-up 72.6 monthsde 2019 | 81.4% at 5 y (77.2–85.8%) | 76.1% at 5 y (71.6–80.9%) | HR 0.70 (95% CI 0.51–0.97)P=0.034Post-hoc analysis with one additional year of follow-up; adjusted hazard ratio. 660 eligible and evaluable women. |
| FFS5-year failure-free survival in the updated analysis (competing-risk methods); co-primary endpoint | long term-updatemedian follow-up 72.6 monthsde 2019 | 76.5% at 5 y (71.5–80.7%) | 69.1% at 5 y (63.8–73.8%) | HR 0.70 (95% CI 0.52–0.94)P=0.016Post-hoc analysis with one additional year of follow-up. |
| Distant recurrence5-year probability of distant metastases as the first site of recurrence | long term-updatemedian follow-up 72.6 monthsde 2019 | 21.4% at 5 y (17.3–26.3%) | 29.1% at 5 y (24.4–34.3%) | HR 0.74 (95% CI 0.55–0.99)P=0.047Isolated vaginal recurrence was the first site of recurrence in one patient (0.3%) in each group, and isolated pelvic recurrence in three women (0.9%) with chemoradiotherapy versus four (0.9%) with radiotherapy alone. |
| OS10-year overall survival; preplanned long-term analysis | long term-updatemedian follow-up 10.1 yearsPost 2025 | 74.4% at 10 y (69.8–79.4%) | 67.3% at 10 y (62.3–72.7%) | HR 0.73 (95% CI 0.54–0.97)P=0.032Adjusted hazard ratio. 660 eligible and evaluable patients. |
| RFS10-year recurrence-free survival (published as recurrence-free survival) | long term-updatemedian follow-up 10.1 yearsPost 2025 | 72.8% at 10 y (67.2–77.6%) | 67.4% at 10 y (61.7–72.4%) | HR 0.74 (95% CI 0.56–0.98)P=0.034Adjusted hazard ratio. |
| OSp53 abnormal tumours (post-hoc molecular subgroup; molecular analysis available for 411 of 660 patients)10-year overall survival in p53 abnormal tumours | exploratorymedian follow-up 10.1 yearsPost 2025 | 52.7% at 10 y (40.8–68.1%) | 36.6% at 10 y (25.0–53.7%) | HR 0.52 (95% CI 0.30–0.91)P=0.021Post-hoc analysis by molecular class. The abstract states that MMRd and POLEmut cancers did not seem to benefit from chemoradiotherapy over radiotherapy alone and that the effects for NSMP cancers were modulated by oestrogen-receptor status. |
| RFSp53 abnormal tumours (post-hoc molecular subgroup; molecular analysis available for 411 of 660 patients)10-year recurrence-free survival in p53 abnormal tumours | exploratorymedian follow-up 10.1 yearsPost 2025 | 52.6% at 10 y (38.3–65.0%) | 37% at 10 y (23.7–50.2%) | HR 0.42 (95% CI 0.24–0.74)P=0.0027Post-hoc analysis by molecular class. |
| RFSp53 abnormal tumours (n=93) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 59% at 5 y | 36% at 5 y | P=0.019Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSPOLE-mutated (POLEmut) tumours (n=51) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 100% at 5 y | 97% at 5 y | P=0.637Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSMismatch repair deficient (MMRd) tumours (n=137) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 68% at 5 y | 76% at 5 y | P=0.428Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSNo specific molecular profile (NSMP) tumours (n=129) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 80% at 5 y | 68% at 5 y | P=0.243Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| Endpoint | Analysis | Chemoradiotherapy | Pelvic radiotherapy alone | Effect |
|---|---|---|---|---|
| OS5-year overall survival; co-primary endpoint | primarymedian follow-up 60.2 monthsde 2018 | 81.8% at 5 y (77.5–86.2%) | 76.7% at 5 y (72.1–81.6%) | HR 0.76 (95% CI 0.54–1.06)P=0.11Adjusted hazard ratio (adjusted for stratification factors). 660 eligible patients were included in the final analysis (330 per arm) of 686 enrolled. |
| FFS5-year failure-free survival; co-primary endpoint | primarymedian follow-up 60.2 monthsde 2018 | 75.5% at 5 y (70.3–79.9%) | 68.6% at 5 y (63.1–73.4%) | HR 0.71 (95% CI 0.53–0.95)P=0.022Hazard ratio adjusted for stratification factors. |
| Grade 3 or worse adverse eventsPatients as reported in the treatment safety analysis (330 per arm)Grade 3 or worse adverse events during treatment | primaryde 2018 | 60% | 12% | P<0.0001198 of 330 patients with chemoradiotherapy versus 41 of 330 with radiotherapy. |
| Grade 2 or worse neuropathyWomen assessed at 3 yearsNeuropathy of grade 2 or worse persisting at 3 years | primaryde 2018 | 8% at 3 y | 1% at 3 y | P<0.000120 women (8%) versus one (1%) at 3 years. |
| OS5-year overall survival in the updated analysis with one additional year of follow-up; co-primary endpoint | long term-updatemedian follow-up 72.6 monthsde 2019 | 81.4% at 5 y (77.2–85.8%) | 76.1% at 5 y (71.6–80.9%) | HR 0.70 (95% CI 0.51–0.97)P=0.034Post-hoc analysis with one additional year of follow-up; adjusted hazard ratio. 660 eligible and evaluable women. |
| FFS5-year failure-free survival in the updated analysis (competing-risk methods); co-primary endpoint | long term-updatemedian follow-up 72.6 monthsde 2019 | 76.5% at 5 y (71.5–80.7%) | 69.1% at 5 y (63.8–73.8%) | HR 0.70 (95% CI 0.52–0.94)P=0.016Post-hoc analysis with one additional year of follow-up. |
| Distant recurrence5-year probability of distant metastases as the first site of recurrence | long term-updatemedian follow-up 72.6 monthsde 2019 | 21.4% at 5 y (17.3–26.3%) | 29.1% at 5 y (24.4–34.3%) | HR 0.74 (95% CI 0.55–0.99)P=0.047Isolated vaginal recurrence was the first site of recurrence in one patient (0.3%) in each group, and isolated pelvic recurrence in three women (0.9%) with chemoradiotherapy versus four (0.9%) with radiotherapy alone. |
| OS10-year overall survival; preplanned long-term analysis | long term-updatemedian follow-up 10.1 yearsPost 2025 | 74.4% at 10 y (69.8–79.4%) | 67.3% at 10 y (62.3–72.7%) | HR 0.73 (95% CI 0.54–0.97)P=0.032Adjusted hazard ratio. 660 eligible and evaluable patients. |
| RFS10-year recurrence-free survival (published as recurrence-free survival) | long term-updatemedian follow-up 10.1 yearsPost 2025 | 72.8% at 10 y (67.2–77.6%) | 67.4% at 10 y (61.7–72.4%) | HR 0.74 (95% CI 0.56–0.98)P=0.034Adjusted hazard ratio. |
| OSp53 abnormal tumours (post-hoc molecular subgroup; molecular analysis available for 411 of 660 patients)10-year overall survival in p53 abnormal tumours | exploratorymedian follow-up 10.1 yearsPost 2025 | 52.7% at 10 y (40.8–68.1%) | 36.6% at 10 y (25.0–53.7%) | HR 0.52 (95% CI 0.30–0.91)P=0.021Post-hoc analysis by molecular class. The abstract states that MMRd and POLEmut cancers did not seem to benefit from chemoradiotherapy over radiotherapy alone and that the effects for NSMP cancers were modulated by oestrogen-receptor status. |
| RFSp53 abnormal tumours (post-hoc molecular subgroup; molecular analysis available for 411 of 660 patients)10-year recurrence-free survival in p53 abnormal tumours | exploratorymedian follow-up 10.1 yearsPost 2025 | 52.6% at 10 y (38.3–65.0%) | 37% at 10 y (23.7–50.2%) | HR 0.42 (95% CI 0.24–0.74)P=0.0027Post-hoc analysis by molecular class. |
| RFSp53 abnormal tumours (n=93) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 59% at 5 y | 36% at 5 y | P=0.019Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSPOLE-mutated (POLEmut) tumours (n=51) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 100% at 5 y | 97% at 5 y | P=0.637Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSMismatch repair deficient (MMRd) tumours (n=137) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 68% at 5 y | 76% at 5 y | P=0.428Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
| RFSNo specific molecular profile (NSMP) tumours (n=129) (molecular subgroup of the 2020 translational analysis; 410 of 423 collected tissue samples classified)5-year recurrence-free survival (primary endpoint of the molecular analysis) | exploratoryLeón-Castillo 2020 | 80% at 5 y | 68% at 5 y | P=0.243Subgroup result of the 2020 translational analysis of PORTEC-3 tissue (the full text calls it a predefined translational research analysis, not powered for molecular subgroups; test for interaction between molecular class and treatment arm not significant: RFS P=0.072, OS P=0.113). The abstract gives no hazard ratio. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.76 | 0.54–1.06 |
| FFS | 0.71 | 0.53–0.95 |
| OS | 0.7 | 0.51–0.97 |
| FFS | 0.7 | 0.52–0.94 |
| Distant recurrence | 0.74 | 0.55–0.99 |
| OS | 0.73 | 0.54–0.97 |
| RFS | 0.74 | 0.56–0.98 |
| OS | 0.52 | 0.3–0.91 |
| RFS | 0.42 | 0.24–0.74 |
Appears in
Sources
de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295-309.
de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019;20(9):1273-1285.
Post CCB, de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial. Lancet Oncol. 2025;26(10):1370-1381.
León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol. 2020;38(29):3388-3397.