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HomeEditor's PickCombination treatment slashes cervical cancer deaths by 40%

Combination treatment slashes cervical cancer deaths by 40%

British researchers are hailing a new cervical cancer treatment as the biggest improvement in 20 years, cutting the risk of death by 40% and with patients remaining disease-free for 10 years.

Combining chemotherapy and radiotherapy, it’s a major milestone for treatment of the disease, said Cancer Research UK.

The Independent reports that scientists at University College London (UCL) and University College London Hospital (UCLH) recently completed a long-term follow-up of patients given a short course of chemotherapy before chemoradiation – a combination of chemotherapy and radiotherapy.

The findings, which follow on from those first presented in October 2023, showed a 40% reduction in the risk of death and a 35% reduction in the risk of cancer returning within at least five years.

Chemoradiation has been the standard treatment for cervical cancer since 1999, but despite improvements in care, cancer returns in up to 30% of cases.

The Interlace phase 3 trial, funded by Cancer Research UK and UCL Cancer Trials Centre, looked at whether a short course of induction chemotherapy before chemoradiation could cut relapses and death among patients with locally advanced cervical cancer that had not spread to other organs.

The results, published in The Lancet, are so clear that experts are calling for the regime to be used across the UK and internationally.

Dr Mary McCormack, lead investigator of the trial from UCL Cancer Institute and UCLH, said: “This approach is a straightforward way to make a positive difference, using existing drugs that are cheap and already approved for use in patients.

“It has already been adopted by some cancer centres and there’s no reason that this shouldn’t be offered to all patients undergoing chemoradiation for this cancer.”

The trial team recruited 500 patients over 10 years from hospitals in the UK, Mexico, India, Italy and Brazil. Patients were randomly allocated to receive either standard treatment or the new treatment combination.

After five years, 80% of those who received a short course of chemotherapy first were alive and 73% had not seen their cancer return or spread.

In the standard treatment group, 72% were alive and 64% had not seen their cancer return or spread. Researchers said that five patients involved in the trial have been disease-free for more than 10 years.

Professor Jonathan Ledermann, senior author of the study from UCL Cancer Institute, said: “The incremental cost for using the drugs in the Interlace trial is low, making this a new treatment that can be easily implemented in all health economies, to significantly improve overall survival.”

Dr Iain Foulkes, executive director of research and innovation at Cancer Research UK, said: “Timing is everything when you’re treating cancer.

“The simple act of adding induction chemotherapy to the start of chemoradiation treatment for cervical cancer has delivered remarkable results in the Interlace trial.

“A growing body of evidence is showing that additional chemotherapy before other treatments, like surgery and radiotherapy, can improve the chances of successful treatment for patients.

“Not only can it reduce the chances of cancer coming back, it can also be delivered quickly, using drugs already available worldwide.”

Study details

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

Mary McCormack, Gemma Eminowicz, Dolores Gallardo et al.

Published in The Lancet on 14 October 2024

Summary

Background
Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

Methods
The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0–50·4 Gy external beam radiotherapy delivered in 20–28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population

Findings
Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46–0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40–0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group.

Interpretation
Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer.

 

The Lancet article – 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 (Open access)

 

The Independent article – Treatment cuts cervical cancer deaths by 40% in ‘biggest breakthrough for decades’ (Open access)

 

See more from MedicalBrief archives:

 

Better use of existing drugs boosts cervical cancer survival – UK study

 

Cervical cancer can be eliminated by 2040: UK health boss

 

Cardiotoxicity risks after chemo treatment

 

Cervical cancer self-screening the answer to reduce fatalities

 

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