As reported in The Lancet by McCormack et al, the phase III INTERLACE trial has shown improved progression-free and overall survival with the addition of induction chemotherapy to standard chemoradiotherapy in patients with locally advanced cervical cancer.
Study Details
In the open-label trial, 500 patients with locally advanced disease (FIGO 2008 stage IB1 disease with nodal involvement or stage IB2, IIA, IIB, IIIB, or IVA disease) from sites in Brazil, India, Italy, Mexico, and the United Kingdom were randomly assigned between November 2012 and November 2022 to receive induction chemotherapy with standard cisplatin-based chemoradiotherapy (n = 250) or chemoradiotherapy alone (n = 250).
Cisplatin-based chemoradiotherapy consisted of once-weekly cisplatin at 40 mg/m² for 5 weeks with 45.0 to 50.4 Gy external-beam radiotherapy delivered in 20 to 28 fractions plus brachytherapy, to achieve a total dose of 70 Gy. Induction chemotherapy consisted of once-weekly carboplatin at AUC 2 plus paclitaxel at 80 mg/m² for 6 weeks. The primary endpoints were progression-free survival and overall survival in the intention-to-treat population.
Progression-Free and Overall Survival
KEY POINTS
- The addition of induction chemotherapy to standard chemoradiotherapy significantly improved progression-free and overall survival in patients with locally advanced cervical cancer.
- At 5 years, progression-free survival was 72% with induction chemotherapy added vs 64% with chemoradiotherapy alone and overall survival was 80% vs 72%.
Median follow-up was 67 months. Progression-free survival at 5 years was 72% in the induction chemotherapy group vs 64% in the control group (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.46–0.91, P = .013). At 3 years, progression-free survival rate was 75% vs 72%.
Overall survival at 5 years was 80% in the induction chemotherapy group vs 72% in the control group (HR = 0.60, 95% CI = 0.40–0.91, P = .015). At 3 years, overall survival was 85% vs 80%.
Adverse Events
Overall, grade ≥ 3 adverse events were observed in 59% of the induction chemotherapy group vs 48% of the control group. Grade 3 or 4 hematologic adverse events occurred in 30% vs 13% of patients, with the most common in the induction chemotherapy group being neutropenia (19% vs 5%). In the induction chemotherapy phase, 22% of patients had grade 3 or 4 adverse events, most commonly neutropenia (7%). No treatment-related deaths were observed.
The investigators concluded: “Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.”
Mary McCormack, PhD, of University College Hospital NHS Trust, London, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.
