Clinical trialPhase 3Cervical cancer

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

Lancet · 2024500 patients

McCormack M, Eminowicz G, Gallardo D, Diez P, Farrelly L, Kent C, et al. Lancet. 2024. 404:1525-1535

Study type: Clinical trial
Study name: INTERLACE (GCIG)
Phase: Phase 3
Design: Randomised, open-label, multicentre trial at 32 centres (Brazil, India, Italy, Mexico, UK)
Sample size: 500 patients
Source: Lancet · 2024
Trial registration: NCT01566240

In plain words

In this study, half of the patients were given six weeks of mild weekly chemotherapy (carboplatin and paclitaxel) before starting the usual chemoradiotherapy (chemotherapy given together with radiotherapy). After five years, 80% of these patients were alive, compared with 72% in the usual-treatment group. Side effects were somewhat more common, but the start of radiotherapy was not delayed (the gap was typically one week).

Key results

72% vs 64%

5-year progression-free survival

HR 0.65 (95% CI 0.46–0.91); p=0.013

80% vs 72%

5-year overall survival

HR 0.60 (95% CI 0.40–0.91); p=0.015

67 months

Median follow-up

59% vs 48%

Grade 3 or higher adverse events

147 of 250 vs 120 of 250

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Paclitaxel (Taxol)

Dose and schedule cards

Chemoradiotherapy with weekly cisplatin (standard)

Locally advanced cervical cancer (IB3 to IVA), and stages IB2 and IIA1 when surgery is not appropriateCycle length: WeeklyOn the page “Cervical cancer” · Locally advanced disease: chemoradiotherapy and its add-ons

Locally advanced cervical cancer (IB3 to IVA), and stages IB2 and IIA1 when surgery is not appropriate

Drug	Dose	Route	Schedule
Cisplatin	40 mg/m² (in INTERLACE, maximum 70 mg per dose)	IV	Once weekly concurrent with external beam radiotherapy, 5 to 6 doses
Pelvic external beam radiotherapy	45 to 50.4 Gy in 20 to 28 fractions	External beam radiotherapy	Concurrent with cisplatin
Brachytherapy	To a total equivalent dose in 2-Gy fractions (EQD2) of 78 to 86 Gy; in KEYNOTE-A18, at least 80 Gy (volume-based) or 75 Gy (point-based)	Intracavitary	After external beam radiotherapy

Cycle length: Weekly
Duration: Cisplatin for 5 to 6 weeks; total radiotherapy course up to 50 days (up to 56 days for unforeseen delays; KEYNOTE-A18 protocol)

In the landmark GOG trial, eligibility required serum creatinine ≤2 mg/dL, white blood cell count ≥3000/mm³ and platelets ≥100,000/mm³, and weekly cisplatin 40 mg/m² for 6 weeks improved survival compared with hydroxyurea. Source for dosing and radiotherapy: the INTERLACE and KEYNOTE-A18 protocols.

On the page “Cervical cancer” · Locally advanced disease: chemoradiotherapy and its add-ons

Weekly induction chemotherapy followed by chemoradiotherapy (INTERLACE)

FIGO 2008 stage IB1 node-positive, IB2, IIA, IIB, IIIB or IVA (70% of patients stage IIB); NCCN: stage IIB to IVACycle length: WeeklyOn the page “Cervical cancer” · Locally advanced disease: chemoradiotherapy and its add-ons

FIGO 2008 stage IB1 node-positive, IB2, IIA, IIB, IIIB or IVA (70% of patients stage IIB); NCCN: stage IIB to IVA

Drug	Dose	Route	Schedule
Induction: 6 weeks
Carboplatin	AUC 2 (maximum 270 mg)	IV	Days 1, 8, 15, 22, 29 and 36
Paclitaxel	80 mg/m² (maximum 162 mg)	IV	Days 1, 8, 15, 22, 29 and 36
Then chemoradiotherapy
Cisplatin	40 mg/m² (maximum 70 mg)	IV	Weekly, up to 5 doses, starting in the first week of radiotherapy
External beam radiotherapy + brachytherapy	45 to 50.4 Gy in 20 to 28 fractions + brachytherapy to a total EQD2 of 78 to 86 Gy	Radiotherapy	Concurrent with cisplatin

Cycle length: Weekly
Duration: 6 weeks of induction, then chemoradiotherapy (median interval in the trial: 7 days)

Cisplatin is started after blood counts have recovered from induction. 92% of patients completed at least 5 induction cycles. Source for doses and caps: protocol NCT01566240.

On the page “Cervical cancer” · Locally advanced disease: chemoradiotherapy and its add-ons

INTERLACE: short induction with carboplatin + paclitaxel

Locally advanced cervical cancer, before cisplatin chemoradiotherapy (off-label use)Cycle length: WeeklyOn the page “Carboplatin (Paraplatin)” · Standard dosing and combination regimens

Locally advanced cervical cancer, before cisplatin chemoradiotherapy (off-label use)

Drug	Dose	Route	Schedule
Induction
Carboplatin	AUC 2	IV	Weekly
Paclitaxel	80 mg/m²	IV	Weekly
Then
Cisplatin + radiotherapy	40 mg/m² weekly, 5 weeks	IV

Cycle length: Weekly
Duration: 6 weeks of induction, then standard chemoradiotherapy

Doses from the INTERLACE trial.

On the page “Carboplatin (Paraplatin)” · Standard dosing and combination regimens

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Induction chemotherapy + chemoradiotherapy (250 patients)

Weekly induction chemotherapy (6 weeks): carboplatin AUC 2 (maximum 270 mg) and paclitaxel 80 mg/m² (maximum 162 mg), both IV on days 1, 8, 15, 22, 29 and 36.

Then (after a median interval of 7 days) the same standard chemoradiotherapy; cisplatin was started in the first week of radiotherapy or as soon as blood counts recovered after induction.

2Standard chemoradiotherapy alone (250 patients)

Cisplatin 40 mg/m² (maximum 70 mg) IV once weekly, up to 5 weeks, with external beam radiotherapy 45.0 to 50.4 Gy in 20 to 28 fractions, plus intracavitary brachytherapy to reach a minimum total dose of 78 to 86 Gy EQD2 (equivalent dose in 2 Gy fractions).

Source of the regimen details: Abstract and Methods section of the paper (Lancet 2024) and ClinicalTrials.gov NCT01566240 (administration days and dose caps)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with locally advanced cervical cancer (FIGO 2008 stage IB1 with lymph node involvement, or stages IB2, IIA, IIB, IIIB or IVA). 70% of patients had stage IIB and 11% stage IIIB disease; pelvic nodes were positive in 43%.

Endpoints

Primary endpoints: progression-free survival and overall survival in the intention-to-treat population.

Safety and side effects

Grade 3 or higher adverse events were reported in 147 (59%) of 250 patients in the induction group and 120 (48%) of 250 patients in the chemoradiotherapy-alone group. Induction chemotherapy did not compromise full delivery of chemoradiotherapy: 85% versus 90% of patients received four or more cycles of cisplatin.

Clinical significance and place in guidelines

A low-cost, widely available strategy using old drugs that improved overall survival. The NCCN guideline (version 2.2026) includes induction chemotherapy followed by chemoradiotherapy as a footnote for stage IIB–IVA. Important: INTERLACE was designed before the immunotherapy era and has not been compared with the KEYNOTE-A18 regimen; combining or choosing between these two strategies is still a research question.

Limitations

Open-label design; long recruitment period (2012 to 2022), during which radiotherapy techniques changed; most patients had stage IIB disease and patients with positive para-aortic nodes were under-represented; no comparison with chemoradiotherapy plus immunotherapy.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.