GOG 157

Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study.

Pubmed

Hypothesis: 6 cycles of carboplatin (AUC 7.5) and paclitaxel (175mg/m2) improves survival compared to 3 cycles.

Site: Ovary

Eligibility: Stage IA/IB (Grade 3 or clear cell) or stage II completely resected

Experimental arm: 6 cycles of AUC 7.5 carboplatin and 175 mg/m2 of Paclitaxel

Standard Arm: 3 cycles of AUC 7.5 carboplatin and 175 mg/m2 of Paclitaxel

Primary Outcome:

Results:
n=457 enrolled; 427 final cohort
69% were stage 1
31% were stage 2

Parameter 3 cycles 6 cycles p-value
5-year recurrence rate 25.4% 20.1% ns
Adjusted Recurrence rate 1 ref 0.761 (0.51 – 1.13) 0.18
Neurotoxicity G4 2% 11% ss
Neutropenia G4 52% 66% ss
Anemia 32% 48% ss

ss: statistically significant
ns: not statistically significant

Conclusions:

  • 3 cycles of chemotherapy are non-inferior to 6 cycles after complete surgical staging
  • Post-hoc analysis PubmedSerous tumors 6 cycles improve survival

Limitations:

  • High dose of Carboplatin (AUC 7.5)
  • High proportion of incompletely staged patients (about 30%)
  • Study likely underpowered to show difference between 3 and 6 cycles, so although the null hypothesis is no difference, there may be a difference which would have been seen in a fully powered study

  1. Adjusted for FIGO stage and grade ↩︎

PORTEC 3

Pubmed

Study Summary by: Dr. Kevin McCool

Title: Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomized, phase 3 trial

Hypothesis: To investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.

Standard Arm: EBRT (48.6 Gy in 1.8 Gy fractions)

Experimental Arm: EBRT (48.6 Gy) Chemotherapy (Cisplatin 50 mg/m2 in weeks 1 and 4 during RT followed by 4 cycles of Carboplatin AUC5 and Paclitaxel 175 mg/m2)

Design: Open-label, randomized, multi-center (UK, Australia, Italy, Canada, France)Inclusion Criteria:
– Endometrioid:

  • Stage IA Grade 3 with with LVSI

  • Stage IB Grade 3

  • Any Stage II or  III.

  • Serous or Clear Cell: Stage IA (with invasion), IB, II, III

Exclusion Criteria (outside of usual): Carcinosarcoma, prior malignancy within 10 years, prior radiotherapy, hormonal therapy, chemotherapy, bulky cervical involvement with radical hysterectomy, residual macroscopic disease

Primary Endpoint: Co-primary endpoints were failure-free survival (FFS) and overall survival (OS)

Outcomes: ChemoRT vs. RT alone (HR and p-value)

  • OS: 81.8% vs.76.6% [HR 0.76 (p=0.109)]
  • FFS: 75.5% vs. 68.6%[HR 0.71 (p=0.022) favoring chemotherapy RT]
  • Subgroup analysis: Stage III patients
    • 5 year FFS = 69.3% vs 58.0% (HR=0.66, p=0.031)
    • 5 year OS = 78.7% vs. 69.8% (HR=0.71, p=0.13)

Serious Adverse Events: ChemoRT vs. RT alone (p-value)

  • Any hematologic: 45% vs. 5% (p<0.0001)
  • GI: 14% vs. 5% (p<0.0001)
  • Neuropathy: 7% vs. 0% (p<0.0001)
  • At 12 months no significant difference in any grade 3 toxicity

Conclusions:

  • Improvement in FFS with the addition of chemotherapy. OS unchanged
  • Significant improvement in FFS
  • Most benefit in patients with stage III
  • Age is a significant predictor on risk adjustment. Patients above 70 benefit from chemoradiation (however toxicity discussion is warranted)