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9th November 2023
A short course of induction chemotherapy (IC) ahead of standard treatment with chemotherapy and radiation reduces the rate of relapse and death in women with locally advanced cervical cancer, according to preliminary study findings presented at the European Society for Medical Oncology (ESMO) Congress 2023.
The INTERLACE phase 3 trial enrolled 500 women with squamous, adeno or adenosquamous carcinoma stages IB1/2 to IVA from hospitals in the UK, Mexico, India, Italy, and Brazil over 10 years.
The median patient age was 46 years, overall most women (77%) had stage II cancer, and more than half (57%) were lymph node negative, researchers reported in an abstract simultaneously published in the Annals of Oncology.
Patients were randomised to receive standard chemoradiation (CRT), consisting of external radiation with weekly cisplatin and brachytherapy, or an initial six-week course of IC with carboplatin AUC2 and paclitaxel 80mg/m2 followed by standard CRT.
Researchers found women who received IC followed by CRT had five-year progression-free survival rates of 73% compared to 64% in the women who had received CRT alone.
The corresponding five-year overall survival rates were 80% for the IC and CRT group versus 72% for the standard care group.
Given these results, the study authors said IC with CRT should be considered a new standard of care, adding that carboplatin and paclitaxel were cheap, accessible and already approved for patient use.
Lead investigator Dr Mary McCormack, honorary lecturer at UCL Cancer Institute and consultant clinical oncologist at University College London Hospitals, said the trial showed this short course of additional chemotherapy could reduce the risk of the cancer returning or death by 35%.
‘This is the biggest improvement in outcome in this disease in over 20 years,’ she added.
The median overall treatment time for CRT was 45 days in both arms, the researchers reported, with a median interval of seven days between IC and CRT.
They added that 92% of IC patients had five or six cycles of carboplatin and paclitaxel.
Of the IC and CRT group, 84% had four or five cycles of cisplatin while the figure was 89% in the CRT alone group.
Grade ≥3 adverse events were seen in 59% of patients in the IC and CRT group compared with 48% of patients in the CRT alone group.
Commenting on the findings, Professor Ana Oaknin, head of the gynecologic tumors unit at the Vall d´Hebron University Hospital, Barcelona, Spain, called the results encouraging, given the high unmet need for new treatments for advanced cervical cancer.
‘However, it is important to consider the population recruited and the large proportion of patients who had node-negative disease, as we know that positive lymph nodes are indicative of a high risk of relapse,’ she added.
‘Further analysis, in terms of nodal status, would be useful in determining the suitability of the induction chemotherapy approach for different relapse risk groups.’
Professor Oaknin, who was not involved in the research, said ongoing, planned trials might provide information on other ways to improve outcomes beyond CRT alone in high-risk locally advanced cervical cancer.
These included the phase 2 ATOMICC trial investigating anti-PD1 therapy with dostarlimab and the phase 3 e-VOLVE Cervical Study trial assessing the use of the monovalent bispecific human IgG1 monoclonal antibody volrustomig.
Women who live and work in areas with higher levels of fine particulate air pollution are at greater risk of developing breast cancer than women who live and work in less polluted places, finds research presented at the European Society of Medical Oncology (ESMO) Congress 2023.
In a matched case-control study, researchers compared home and workplace air pollution exposure in 2,419 French women diagnosed with breast cancer against the exposure of 2,984 women without the disease from 1990 to 2011.
They found a statistically significant linear increase in breast cancer risk related to mean fine particulate matter (PM2.5) exposure, with a 28% increase in risk with an increment of 10 µg/m3 of PM2.5.
Lead author Professor Béatrice Fervers, head of prevention, cancer environment department, Léon Bérard Comprehensive Cancer Centre, France, said: ‘This contrasts with previous research which looked only at fine particle exposure where women were living, and showed small or no effects on breast cancer risk.’
In a study abstract published in the Annals of Oncology, the research term explained cases were matched to randomly selected controls based on several variables including place of residence, age and menopausal status.
All participants were drawn from the prospective E3N cohort – the French element of the European EPIC Study, coordinated by the International Agency for Research on Cancer.
Researchers using a Land Use Regression model to estimate annual mean PM2.5, coarse particulate matter (PM10) and nitrogen dioxide (NO2) and assigned them to women based on geocoded home and workplace addresses.
Mean exposure was calculated for each woman from the time they were included in the E3N cohort to their index date – the date of diagnosis of cases.
For PM10 and NO2 exposure, researchers found a numerical, but statistically non-significant, increased risk with an incremental increase of 10 µg/m3.
Hormone receptor or menopausal status did not affect any of the results, they added.
Commenting on the findings, Professor Charles Swanton, clinician scientist at the Francis Crick Institute in London, UK, said fine particulate matter can penetrate deep into the lungs, entering the blood stream and then being absorbed into breast and other tissues.
Professor Swanton, who presented research at ESMO Congress 2022 suggesting how PM2.5 particles may trigger lung cancer in non-smokers, said there was already evidence that air pollutants can change breast architecture.
‘It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumour promotion possibly through inflammatory processes, similar to our observations in non-smokers with lung cancer,’ he said.
‘There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression and progression of breast tumours.’
The French research comes weeks after US National Institute of Health researchers published data in the Journal of the National Cancer Institute showing living in an area with high levels of fine particulate air pollution was significantly associated with an increased risk of breast cancer incidence.
Professor Jean-Yves Blay, ESMO director of public policy, said there was strong epidemiological and biological evidence for the link between PM2.5 particle exposure and cancer, with good clinical and economic reasons for reducing pollution to prevent cancers.
In September 2023, the European Parliament adopted in plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, reflecting ESMO’s recommendations to set the annual limit value for PM2.5 at 5 µg/m³.
This adoption opens interinstitutional negotiations between the co-legislators – European Parliament, European Commission and EU Council – to agree on the final text of the directive.