Background
INTERLACE was a phase III randomized trial (n=500) evaluating whether a short course of induction carboplatin-paclitaxel chemotherapy administered before standard concurrent chemoradiotherapy (CRT) could improve outcomes in locally advanced cervical cancer (FIGO 2008 IB1 node-positive, IB2, II, IIIB, IVA). The rationale was that induction chemotherapy could reduce tumor burden, address micrometastatic disease, and potentially sensitize tumors to subsequent CRT.
Interventions and follow up
Arm A (CRT alone): Standard cisplatin-based concurrent chemoradiotherapy (cisplatin 40 mg/m² weekly + EBRT + brachytherapy)
Arm B (induction + CRT): Induction carboplatin AUC 2 + paclitaxel 80 mg/m² weekly ×6 weeks → standard concurrent chemoradiotherapy
Primary endpoints: PFS and OS
Median follow-up: 64 months
Arm B (induction + CRT): Induction carboplatin AUC 2 + paclitaxel 80 mg/m² weekly ×6 weeks → standard concurrent chemoradiotherapy
Primary endpoints: PFS and OS
Median follow-up: 64 months
Results
5-yr PFS: 72% (induction) vs 64% (CRT); HR 0.65, 95% CI 0.46–0.91, P=.013
5-yr OS: 80% vs 72%; HR 0.60, 95% CI 0.40–0.91, P=.015
Absolute gain: ~8% PFS and ~8% OS; benefit consistent across tumor stages and histologies
5-yr OS: 80% vs 72%; HR 0.60, 95% CI 0.40–0.91, P=.015
Absolute gain: ~8% PFS and ~8% OS; benefit consistent across tumor stages and histologies
Adverse events
During induction: Grade ≥3 AE 42% (predominantly hematologic); neutropenia led to dose modifications
CRT completion: 89% (induction) vs 93% (CRT alone); no significant increase in late CRT-related toxicity
CRT completion: 89% (induction) vs 93% (CRT alone); no significant increase in late CRT-related toxicity
Conclusions
Induction carboplatin-paclitaxel before CRT significantly improved 5-year PFS and OS in locally advanced cervical cancer, with a clinically meaningful absolute benefit of ~8% in both endpoints, establishing induction chemotherapy as a new standard-of-care option in this setting.
Key Limitations
Open-label trial; longer treatment duration (induction adds 6 weeks) may affect feasibility in resource-limited settings; CRT completion rate slightly lower in induction arm; brachytherapy not uniformly specified; concurrent with KEYNOTE-A18 (both published 2024 in Lancet) — optimal sequencing or combination with pembrolizumab unknown; no biomarker selection.
Clinical Context
INTERLACE and KEYNOTE-A18 were published in Lancet 2024, both transforming LACC management. INTERLACE asks whether induction chemo before CRT improves outcomes; KEYNOTE-A18 asks whether pembrolizumab with CRT improves outcomes; both answered yes. The potential combination of induction chemo plus pembrolizumab plus CRT is under active investigation. INTERLACE may be particularly relevant where immunotherapy access is limited, and ESMO/ASCO guidance now recognizes induction chemo as an option for LACC.