The phase III INTERLACE trial, published in The Lancet, reveals that incorporating induction chemotherapy into the standard treatment regimen of chemoradiotherapy significantly enhances both progression-free and overall survival in patients battling locally advanced cervical cancer. This multi-center study conducted across Brazil, India, Italy, Mexico, and the United Kingdom, marks a significant step forward in the management of this challenging disease.
Study Design and Methodology
The open-label trial enrolled 500 patients with locally advanced cervical cancer (FIGO 2008 stage IB1 with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA). Participants were randomized to receive either induction chemotherapy followed by cisplatin-based chemoradiotherapy (n = 250) or chemoradiotherapy alone (n = 250) between November 2012 and November 2022.
The chemoradiotherapy regimen consisted of weekly cisplatin (40 mg/m²) for 5 weeks, combined with external-beam radiotherapy (45.0 to 50.4 Gy in 20 to 28 fractions) and brachytherapy, targeting a total dose of 70 Gy. The induction chemotherapy arm received weekly carboplatin (AUC 2) plus paclitaxel (80 mg/m²) for 6 weeks. The primary endpoints were progression-free survival and overall survival.
Significant Survival Benefits
After a median follow-up of 67 months, the addition of induction chemotherapy demonstrated a notable improvement in progression-free survival. The 5-year progression-free survival rate was 72% in the induction chemotherapy group compared to 64% in the control group (HR = 0.65, 95% CI = 0.46–0.91, P = .013). The 3-year progression-free survival rates were 75% and 72%, respectively.
Overall survival also saw a significant boost with the addition of induction chemotherapy. The 5-year overall survival rate was 80% in the induction chemotherapy group versus 72% in the control group (HR = 0.60, 95% CI = 0.40–0.91, P = .015). At 3 years, overall survival rates were 85% and 80%, respectively.
Adverse Event Profile
While the addition of induction chemotherapy improved survival outcomes, it was also associated with a higher incidence of adverse events. Grade ≥ 3 adverse events were observed in 59% of the induction chemotherapy group compared to 48% of the control group. Specifically, grade 3 or 4 hematologic adverse events occurred in 30% versus 13% of patients, with neutropenia being the most common (19% vs 5%). During the induction chemotherapy phase, 22% of patients experienced grade 3 or 4 adverse events, primarily neutropenia (7%). Importantly, no treatment-related deaths were reported.
Expert Commentary
According to Mary McCormack, PhD, of University College Hospital NHS Trust, London, and corresponding author of The Lancet article, “Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.”
The study was funded by Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.
