PORTEC 3: Adjuvant chemotherapy vs. radiotherapy in high-risk endometrial cancer
Stephanie M de Boer
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Disease Site: High-risk endometrial cancer
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Publication Title: 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
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Year of Publication: 2018
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Hypothesis: The study hypothesized that adjuvant chemoradiotherapy would improve survival outcomes compared to pelvic radiotherapy alone in women with high-risk endometrial cancer.
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Inclusion Criteria: Women with FIGO 2009 stage I endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion, endometrioid-type stage II or III, or stage I to III with serous or clear cell histology.
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Exclusion Criteria: Uterine sarcomas, previous malignancy within 10 years, prior pelvic radiotherapy, hormonal therapy or chemotherapy, and certain medical conditions like inflammatory bowel disease or severe neuropathy.
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Primary Endpoint: Overall survival and failure-free survival.
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Experimental Arm(s): Radiotherapy (48.6 Gy in 1.8 Gy fractions) plus chemotherapy (two cycles of cisplatin 50 mg/m² during radiotherapy followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m²).
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Control Arm: Radiotherapy alone (48.6 Gy in 1.8 Gy fractions).
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Results:
Outcome Experimental Arm Control Arm p-value Hazard Ratio Overall Survival (5-year) 81.8% 76.7% 0.11 0.76 (95% CI 0.54-1.06) Failure-Free Survival (5-year) 75.5% 68.6% 0.022 0.71 (95% CI 0.53-0.95) Grade ≥3 Toxicities 60% 12% <0.0001 -
- Subgroup Analysis: Stage III Patients:
| Outcome | ChemoRT | RT Alone | Hazard Ratio (HR) with p-value |
|---|---|---|---|
| 5-year FFS | 69.3% | 58.0% | HR 0.66 (p=0.031) |
| 5-year OS | 78.7% | 69.8% | HR 0.71 (p=0.13) |
- Serious Adverse Events: ChemoRT vs. RT alone (p-value):
| Adverse Event | ChemoRT | RT Alone | p-value |
|---|---|---|---|
| Any Hematologic | 45% | 5% | <0.0001 |
| GI | 14% | 5% | <0.0001 |
| Neuropathy | 7% | 0% | <0.0001 |
Note: At 12 months, there was no significant difference in any grade 3 toxicity between the two treatment groups.
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Conclusions: Adjuvant chemoradiotherapy did not significantly improve 5-year overall survival compared to radiotherapy alone, although it did improve failure-free survival, indicating a notable reduction in the risk of disease recurrence. Importantly, the study highlighted that older women, particularly those aged 70 years or older, benefited significantly from chemoradiotherapy in terms of failure-free survival. Patients with stage III disease experienced an 11% absolute improvement in failure-free survival, emphasizing the value of chemoradiotherapy for certain subgroups, such as those with advanced disease and older patients.
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Limitations: The study acknowledges potential limitations such as the inclusion criteria, the balance of treatment arms regarding patient characteristics, and the open-label design which may introduce bias.