In the phase III EORTC-55994 trial reported in the Journal of Clinical Oncology, Kenter et al found no significant difference in overall survival with neoadjuvant chemotherapy followed by surgery vs standard concomitant chemoradiotherapy in patients with stage IB2 to IIB cervical cancer.
Study Details
In the multicenter trial, 626 women were randomly assigned between May 2022 and January 2014 to receive neoadjuvant chemotherapy followed by surgery (n = 314) or concomitant chemoradiotherapy (n = 312). Neoadjuvant chemotherapy consisted of platinum chemotherapy at a minimum cumulative cisplatin dose of 225 mg/m2 and a cisplatin dose equivalent of at least 75 mg/m2 every 3 weeks; combination chemotherapy was permitted. Concomitant chemoradiotherapy consisted of cisplatin at five or six weekly doses of 40 mg/m2 during radiotherapy; external-beam radiotherapy was given at a total dose of 45 to 50 Gy to the pelvis followed by brachytherapy. The primary endpoint was 5-year overall survival in the intent-to-treat population.
Key Findings
Median follow-up was 8.7 years. Protocol treatment was completed by 71% of patients in the group that received neoadjuvant chemotherapy followed by surgery vs 82% in the group that received concomitant chemoradiotherapy; primary reasons for failure to complete protocol treatment were toxicity (9.6%) and progressive disease (6.7%) in the group given neoadjuvant chemotherapy followed by surgery and toxicity (7.4%) and patient refusal (4.2%) in the group given concomitant chemoradiotherapy. Radiotherapy after completion of neoadjuvant chemotherapy followed by surgery was given to 48% of patients; surgery was performed in 8% of patients after completion of concomitant chemoradiotherapy.
Overall survival at 5 years in the intent-to-treat population was 72% (95% confidence interval [CI] = 66%–77%) with neoadjuvant chemotherapy followed by surgery vs 76% (95% CI = 70%–80%) with concomitant chemoradiotherapy. Median overall survival was not estimable in both groups (hazard ratio for concomitant chemoradiotherapy group vs neoadjuvant chemotherapy followed by surgery group = 0.84, 95% CI = 0.64–1.12, P = .240).
Progression-free survival at 5 years was 57.0% (95% CI = 51.1%–62.4%) with neoadjuvant chemotherapy followed by surgery vs 65.6% (95% CI = 59.9%–70.7%) with concomitant chemoradiotherapy. Median progression-free survival was 12.2 months (95% CI = 5.4 months to not estimable) with neoadjuvant chemotherapy followed by surgery vs not estimable (95% CI = 15.0 months to not estimable) with concomitant chemoradiotherapy (HR for concomitant chemoradiotherapy vs neoadjuvant chemotherapy followed by surgery group = 0.72, 95% CI = 0.57–0.93, P = .010).
Short-term grade ≥ 3 adverse events occurred in 41% of the group given neoadjuvant chemotherapy followed by surgery vs 23% of the group given concomitant chemoradiotherapy. Long-term grade ≥ 3 adverse events occurred in 21% of patients given concomitant chemoradiotherapy vs 15% of those given neoadjuvant chemotherapy followed by surgery. Health-related quality of life measured by the EORTC QLC-C30 showed no relevant differences between groups.
The investigators concluded: “This trial failed to demonstrate superiority in favor of the neoadjuvant chemotherapy followed by surgery arm but resulted in acceptable morbidity and [health-related quality of life] in both arms.”
Gemma G. Kenter, MD, PhD, of the Center Gynecologic Oncology Amsterdam, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: This trial was supported by a grant from the EORTC Cancer Research Fund. For full disclosures of the study authors, visit ascopubs.org.
