Interlace Trial
Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial - PubMed
Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.
Mary McCormack
Hypothesis
Adding induction chemotherapy before standard cisplatin-based chemoradiotherapy improves progression-free survival (PFS) and overall survival (OS) compared to chemoradiotherapy alone in patients with locally advanced cervical cancer.
Inclusion Criteria
- Adults (≥18 years) with FIGO 2008 stage IB1 (with nodal involvement), IB2, IIA, IIB, IIIB, or IVA cervical cancer.
- Histology: squamous, adenocarcinoma, or adenosquamous.
- Fit for radical treatment and no para-aortic lymph node involvement.
Exclusion Criteria
- FIGO 2008 stage IIIA disease.
- Positive lymph nodes above the aortic bifurcation.
Primary End Point
- Progression-free survival (PFS)
- Overall survival (OS)
Experimental Arm(s)
- Induction chemotherapy regimen:
- Carboplatin AUC 2 and paclitaxel 80 mg/m² weekly for 6 weeks.
- Followed by standard chemoradiotherapy starting in week 7.
- Standard chemoradiotherapy regimen:
- Cisplatin 40 mg/m² weekly for 5 weeks.
- External beam radiotherapy (EBRT) 45.0–50.4 Gy in 20–28 fractions.
- Brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy.
Control Arm (or Standard Therapy)
- Standard chemoradiotherapy regimen:
- Cisplatin 40 mg/m² weekly for 5 weeks.
- EBRT 45.0–50.4 Gy in 20–28 fractions.
- Brachytherapy as per the experimental arm.
Results
| Outcome | Induction Chemo + Chemoradiotherapy | Chemoradiotherapy Alone | p-value | Hazard Ratio (HR) |
|---|---|---|---|---|
| 5-year Progression-free Survival (PFS) | 72% | 64% | 0.013 | 0.65 (95% CI 0.46–0.91) |
| 5-year Overall Survival (OS) | 80% | 72% | 0.015 | 0.60 (95% CI 0.40–0.91) |
| Grade 3 or greater adverse events | 147 (59%) | 120 (48%) | - | - |
| Haematological toxicities | 74 (30%) | 32 (13%) | - | - |
Top Toxicities
| Toxicity Type | Induction Chemo + Chemoradiotherapy (n=250) | Chemoradiotherapy Alone (n=250) |
|---|---|---|
| Grade 3-4 Haematological Toxicity | 74 (30%) | 32 (13%) |
| Neutropenia | 48 (19%) | 13 (5%) |
| Anaemia | 13 (5%) | 9 (4%) |
| Thrombocytopenia | 13 (5%) | 5 (2%) |
| Non-haematological Toxicity | 109 (44%) | 107 (43%) |
| Diarrhoea | 20 (8%) | 31 (12%) |
| Fatigue, muscle weakness, or joint pain | 28 (11%) | 14 (6%) |
| Infection | 14 (6%) | 13 (5%) |
| Abdominal or pelvic pain | 13 (5%) | 18 (7%) |
Conclusions
Induction chemotherapy followed by chemoradiotherapy significantly improves both progression-free survival and overall survival in patients with locally advanced cervical cancer compared to chemoradiotherapy alone. However, it leads to higher haematological toxicities.
Limitations
- The trial excluded patients with FIGO 2008 stage IIIA or para-aortic lymph node involvement, which limits the generalizability to the highest-risk groups.
- Recruitment took 10 years, and variations in radiotherapy techniques may have affected outcomes. Although its important to recognize that improvements in radiation techniques, such as IMRT improves toxicity compared to standard chemoRT and not the survival.