Phase III Randomized Trial of 12 Versus 3 Months of Maintenance Paclitaxel in Patients with Advanced Ovarian Cancer After Complete Response to Platinum and Paclitaxel-Based Chemotherapy: A Southwest Oncology Group and Gynecologic Oncology Group Trial (GOG178)

Disease site

Ovaries 

Publication month/year

July, 2003

Study question

To verify whether continuing paclitaxel for an extended period of time in women with advanced ovarian cancer who had achieved a complete response to platinum/paclitaxel-based chemotherapy could prolong their progression-free survival and affect ultimate survival.

Type of study

Randomised controlled trial (RCT)

Interventions compared

3 cycle paclitaxel vs. 12 cycle paclitaxel

Experimental arm (Intervention)

12 cycle paclitaxel

Control arm

3 cycle paclitaxel

Primary outcome

Progression-free survival (PFS)

Secondary outcome
  • Overall survival 
  • Disease Recurrence
  • Toxicity 
Inclusion criteria
  • Histological confirmed stages III/IV:
    • Ovarian cancer
    • Fallopian-tube cancer
    • Primary carcinoma of peritoneum
  • Being treated for at least 5 to 6 cycles of platinum/paclitaxel-based chemo regimen
  • Having a clinically defined complete response to primary platinum/paclitaxel-based chemotherapy.
    • Clinically defined complete response involves no cancer-related symptoms, normal physical examination, normal CT and X-Ray of the abdomen and pelvis, and CA-125 ≤ 35 U/mL. 
Exclusion criteria
  • Patients with prior treatment on a Southwest Oncology Group (SWOG) or Gynecologic Oncology Group (GOG) chemotherapy regimens where either PFS or overall survival were endpoints. 
  • Patients with ≥ grade 2 neuropathy from prior therapy.
Results
Intervention arm Control arm
Randomised(n) 134 128
Received treatment(n) 12 cycle paclitaxel 3 cycle paclitaxel
Progression-free Survival 20 events 34 events
Sensory Neuropathy (Grade 2) 18 14
Sensory Neuropathy (Grade 3) 5 1
Notes on the table
  • Unadjusted log-rank test and adjusted Cox model analysis demonstrate a statistically significant difference in progression-free survival in favour of the 12-cycle treatment arm. (p-value = 0.0035 and 0.0023), respectively. Cox model—adjusted hazard ratio of 3 cycle versus 12 cycle treatment was 2.31 (95% CI 1.08—4.94).
  • Estimated hazard ratio posttreatment versus during treatment was 5.80 (95% CI 2.09—16.10) suggesting that there is a higher risk for disease progression after stopping treatment.
  • There were no other significant differences in the side effect profiles between the 2 treatment arms. 
Overall survival

17 deaths were recorded throughout the entire study. No significant difference between both treatment arms.

Conclusions
  • The study has demonstrated that potential impact of maintenance paclitaxel therapy on progression of advanced ovarian cancer. Moreover, the study shows that the toxicity profile of such extended therapy is not severe enough to negate its benefits. 

  • Lowering the regimen’s dose will reduce the toxicity associated with maintenance therapy while preserving its efficacy on progression free survival.

Study limitations
  • The control arm is a 3-cycle paclitaxel regimen which is not based on any evidence-based studies. As a matter of fact, maintenance therapy for advanced ovarian cancer was never addressed in the literature prior to the date of this study. 
  • Small sample size
  • Cannot be generalized due to the strict inclusion and exclusion criteria
  • The study did not test the impact of drug regimen doses on the magnitude of effect on survival outcomes.
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