As reported in The Lancet Oncology by Mileshkin et al, the phase III OUTBACK trial has shown no survival benefit with adjuvant carboplatin/paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy as primary treatment in patients with locally advanced cervical cancer.
Study Details
In the open-label trial, 919 eligible patients from sites in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the United States were randomly assigned between April 2011 and June 2017 to receive standard cisplatin-based chemoradiotherapy consisting of cisplatin at 40 mg/m² once weekly for 5 weeks during radiotherapy with 45.0 to 50.4 Gy external-beam radiotherapy delivered in 1.8-Gy fractions (chemoradiotherapy-alone group, n = 456) or standard cisplatin-based chemoradiotherapy followed by four cycles of carboplatin at AUC 5 and paclitaxel at 155 mg/m² on day 1 of 21-day cycles (adjuvant chemotherapy group, n = 463).
The primary endpoint was overall survival at 5 years in the intent-to-treat population. A total of 92 patients in the adjuvant chemotherapy group did not start adjuvant chemotherapy.
Overall Survival
At data cutoff (in April 2021), the median follow-up was 60 months (interquartile range [IQR] = 45–65 months). Overall survival at 5 years was 72% (95% confidence interval [CI] = 67%–76%) in the adjuvant chemotherapy group vs 71% (95% CI = 66%–75%) in the chemoradiotherapy-alone group (hazard ratio [HR] = 0.90, 95% CI = 0.70–1.17, P = .81). The 5-year cumulative incidence of cervical cancer–specific death (P = .21) was 21% (95% CI = 17%–26%) vs 24% (95% CI = 20%–28%).
Progression-free survival rates were 70% vs 66% at 3 years (HR = 0.86, 95% CI = 0.69–1.08, P = .17) and 63% vs 62% at 5 years (HR = 0.86, 95% CI = 0.69–1.08, P = .58). Isolated locoregional recurrence occurred in 12% vs 11% of patients; distant recurrence occurred in 13% vs 15%.
Adverse Events
Among 361 patients in the adjuvant chemotherapy group and 453 in the chemoradiotherapy-alone group in the safety population, grade ≥ 3 adverse events occurred in 81% of the adjuvant chemotherapy group vs 62% of the chemoradiotherapy-alone group (P < .0001). The most common adverse events in the adjuvant chemotherapy group were decreased lymphocytes (58% vs 46% in the chemoradiotherapy-alone group), decreased neutrophils (20% vs 8%), and anemia (18% vs 8%).
KEY POINTS
- The addition of adjuvant carboplatin/paclitaxel chemotherapy following standard cisplatin-based chemoradiotherapy did not improve 5-year survival patients with locally advanced cervical cancer.
- Overall survival at 5 years was 72% vs 71%.
Serious adverse events occurred in 30% vs 22% of patients, most commonly infectious complications. No treatment-related deaths were observed.
The investigators concluded: “Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting.”
Linda R. Mileshkin, MD, of the Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the National Health and Medical Research Council and National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
