PORTEC 3

PORTEC 3
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 - PubMed
Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L’Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.
  • Disease Site: High-risk endometrial cancer

  • 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

  • Year of Publication: 2018

  • Hypothesis: The study hypothesized that adjuvant chemoradiotherapy would improve survival outcomes compared to pelvic radiotherapy alone in women with high-risk endometrial cancer.

  • 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.

  • 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.

  • Primary Endpoint: Overall survival and failure-free survival.

  • 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).

  • Control Arm: Radiotherapy alone (48.6 Gy in 1.8 Gy fractions).

  • 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.

  • 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.

  • 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.