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 1

Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial

Pubmed

Hypothesis:
Addition of external beam radiation after surgery in early stage endometrial cancer improves survival

Site:
Endometrium

Experimental arm:
Surgery followed by 46 Gy in 2 Gy daily fractions, 3 or 4 field technique (Fields: superior border at L5/S1)

Standard Arm:
Surgery alone

Eligibility Criteria

  • TAH/BSO without routine LND with these criteria
    Invasion Grade
    >50% (deep) 1
    any 2
    <50% superficial 3
  • WHO score of 0-2
  • Histologies allowed:
    • Endometrioid (also including adenocarcinoma with squamous features)
    • Adenocarcinoma not otherwise specified
    • Adenosquamous carcinoma
    • Papillary serous carcinoma
    • Clear-cell carcinoma

Primary Outcome:
Locoregional recurrence and overall survival

Results:

Outcome EBRT Observation p-value
Locoregional Recurrences 4% 14% SS
Overall Survival** 81% 84% NS
Major Toxicity 25% 6% SS
  • 73% recurrences in the vagina. Rate of distal mets same ~7% each arm
  • Prognostic Factors: Age >60, G3, IC predictive for LR; If 2 of 3 criteria, LR 23% vs. 4% (SS)

Conclusions:
Postoperative radiation improves locoregional control, but no survival benefit


See Radiation Oncology WikiBook for more details ↩︎

GOG 99

GOG 99

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

Pubmed

Hypothesis:
Addition of external beam radiation to postoperative therapy in intermediate risk endometrial cancer improves recurrence free survival

Site: Endometrium

Study population:
Inclusion: Derived from GOG 33

  • Intermediate Group: Any myometrial invasion with any grade and negative lymph node involvement i.e ([FIGO] stage IB, IC, IIA (occult), and IIB [occult]) – 5-year recurrence rate of 20 – 25%
  • Lymph node – Sampling/debulking if suspicious; Full lymphadenectomy if no enlarged or suspicious nodes
  • Revised during the course of study to enroll only “high intermediate risk” group : Expected 25% recurrence risk:
GOG 99 High Intermediate risk Group. Also used in GOG 249
    -  Age
    -  G2-3 tumor
    -  LVI
    -  Outer 1/3 myometrial invasion

1) >70 yrs old with only 1 other risk factor
2) >50 yrs old with 2 risk factors
3) any age with 3 risk factors

Excluded: High risk pathologies i.e. Clear cell and Papillary Serous, laparoscopic surgery excluded.

Experimental arm:
190 patients: External beam radiation 50.4 Gy given in 28 fractions. No Vag brachytherapy

Standard Arm:
202 patients: No additional therapy after surgery

Outcomes: Experimental arm vs. Standard arm (OR and p-values)

  • Primary Outcome (Recurrence Free @ 24 months) – 3% vs. 12% (OR – 0.42, p=0.007)
  • Secondary Outcome (Overall Survival @ 48 months) – 92% vs. 86% (OR – 0.86, p = 0.557)
  • Local Recurrences – 1.6% vs. 8.9% (p = ss)
  • Significantly Different Toxicity (Grade 2 or greater):
    • Hematologic: 7.4% vs 2.5% (p = ss)
    • GI : 34% vs. 2.5% (p = ss)

Conclusions:

  • Radiation reduced local recurrences but did not improve overall survival
  • Many deaths in the study were not endometrial cancer specific, therefore study underpowered to detect difference in overall survival even if it existed.
  • HIR group (132 total patients) : Defined above
    • Reduction in Hazard of isolated recurrence (RH: 0.37)
    • Reduction in Distant metastatic recurrence related to RT (RH: 0.46)
  • 2/3rd of recurrences and 2/3rd of cancer deaths in this group.
  • HIR – 19% improvement in cumulative recurrence at 24 months compared to no adjuvant therapy group vs LIR group 4% improvement compared to no adjuvant therapy group.

This study was the basis of GOG 249 selection criteria.


SOLO-1: Maintenance Olaparib in Newly Diagnosed Advanced Ovarian Cancer

Title: Maintenance Olaparib in Newly Diagnosed Advanced Ovarian Cancer

Hypothesis: Maintenance PARP-i after initial therapy in high-grade ovarian carcinoma improves progression free survival.

Standard Arm: Placebo

Experimental Arm: Olaparib 300 mg bid daily x 2 years

Design: Double blinded randomized controlled phase 3 study

Inclusion Criteria: High-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer with mutation in BRCA1, BRCA2 (germline or somatic)

Primary Endpoint: PFS or death at 3 years

Outcomes: Experimental vs. Standard arm (p-value)

PFS/death at 3 years: 60% vs. 27% (p<0.001)

Median time to subsequent therapy: 51.8 months vs. 15.1 months (HR – 0.30, p<0.001)

Serious Adverse Events:Experimental vs. Standard arm (p-value)

Anemia (G3/G4): 22% vs. 2% (p=s.s.)

Neutropenia (G3/G4): 9% vs. 5% (p=s.s.)

AML: 3/260 (1%) vs. 0/130 (0%) (p=n.s)

New Primary Cancer: 5/260 (2%) vs. 3/130 (2%) (p=n.s.)

Pneumonitis/Interstitial Lung Disease: 5/260 (2%) vs. 0 (p=n.s)

Conclusion: Addition of Olaparib 300mg bid for two years maintenance after completion of primary chemotherapy and debulking surgery in BRCA 1/2 (both germline or somatic) increases progression free survival or risk of death at 3 years.

GOG 161

Phase III Trial of Ifosfamide With or Without Paclitaxel in Advanced Uterine Carcinosarcoma: A Gynecologic Oncology Group Study

Pubmed

Hypothesis:Addition of paclitaxel to ifosfamide improve OS/ PFS in carcinosarcoma (GOG 108 there was no advantage to the combination of ifosfamide and cisplatin vs. ifosfamide alone related to median survival. GOG 130-B revealed a substantial response rate of carcinosarcoma to single-agent paclitaxel.)

Site: Uterus

Experimental arm: Ifosfamide 1.6 g/m2 IV daily for 3 days (1.2 g/m2 for irradiated patients) plus Paclitaxel 135 mg/m2 by 3 hour infusion day 1

Standard Arm: Ifosfamide 2 g/m2 IV for 3 days

Mesna iv or oral 1

Primary Outcome: Overall survival (OS)

Results:

Outcome Ifos Ifos Taxol p-value
OS (months)2 8.4 13.5 SS
PFS (months) 3.6 5.8 SS
ORR3 29% 45% SS
Toxicity
G1-4 neuropathy 8% 30% SS
Alopecia 40% 58% SS
Thrombocytopenia 11% 46% SS
G3-G4 Neutropenia 53% 44% NS

CNS related toxicity was similar in two arms

Conclusions:

  • Combination chemotherapy with Ifosfamide Taxol improves OS.
  • Treatment effect not different based on prior radiation or previous site of disease
  • No Quality of life assessments in this study

  1. Read GOG 261 design and mesna dosing schedules ↩︎
  2. Hazard Ratio: 0.69 (95% CI, 0.49 to 0.97; P = .03) ↩︎
  3. Overall Response Rate ↩︎