2017 Annual Congress of the European Society for Medical Oncology

Priscilla Lynch presents a round-up of research presented at ESMO 2017

ESMO 2017 Congress highlights importance of cancer prevention

This year’s Annual Congress of the European Society for Medical Oncology (ESMO) in Madrid, Spain, was a truly global event, with nearly 24,000 participants from 131 countries. The 10 countries with the most delegates were the US, France, Spain, UK, Germany, Italy, Switzerland, China, Japan and Russia.

A record number of abstracts were submitted, with 1,736 selected for presentation. Ground-breaking research was revealed in 55 late-breaking abstracts.

ESMO 2017 research was simultaneously published in leading scientific journals, including the New England Journal of Medicine (NEJM), Lancet Oncology and Annals of Oncology.

Practice-changing studies presented at ESMO 2017 include:

PACIFIC: New standard of care for locally-advanced, unresectable stage III non-small-cell lung cancer (NSCLC).

IFCT-0302: Questioned regular computed tomography (CT) scans in resected NSCLC.

COMBI-AD: New adjuvant treatment option for high-risk melanoma.

CheckMate 238: Improved adjuvant therapy for patients with surgically-resected stage III/IV melanoma at high risk of relapse.

LORELEI: Greater tumour shrinkage in oestrogen receptor-positive and HER2-negative early breast cancer.

MONARCH 3: Improved outcomes with a new initial strategy for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer.

ARIEL 3: New maintenance therapy for recurrent ovarian cancer.

RANGE: Promising treatment for advanced or metastatic urothelial cancer.

CheckMate 214: Combination therapy reduces kidney cancer death risk.

Researchers also highlighted the importance of preventing cancer. “Forty per cent of cancers are preventable,” said Prof Josep Tabernero, ESMO President-Elect.

“Oncology is not only about medicines,” he continued. “We should emphasise lifestyle changes that would reduce the incidence of cancer; stop smoking, reduce alcohol intake, having a balanced diet low in red meat, exercise and avoid exposure to substances that have been shown to be carcinogenic.’’

On the policy front, there were debates about the sustainability and cost-effectiveness of cancer treatments. Biosimilars, which are new in oncology, were presented as a valid option to facilitate access to treatment and alleviate the strain on healthcare systems.

Held in collaboration with the European Association for Cancer Research (EACR), the tag-line for ESMO 2017 was ‘Integrating science into oncology for a better patient outcome’.

Abdominal fat a key cancer driver for post-menopausal women

Body fat distribution in the trunk is more important than body weight when it comes to cancer risk in postmenopausal women, according to a study presented at the ESMO 2017 Congress in Madrid.

The findings put a new spin on weight management priorities for women in this age group who are prone to abdominal weight gain, said study investigator Ms Line Mærsk Staunstrup, MSc, a PhD student with Nordic Bioscience and ProScion in Herlev, Denmark.

“When assessing cancer risk, body mass index (BMI) and fat percentage may not be adequate measures, as they fail to assess the distribution of fat mass,” she explained. “Avoiding central obesity may confer the best protection.”

The findings come from the Prospective Epidemiologic Risk Factor study, an observational, prospective cohort study designed to get a better understanding of age-related diseases in Danish postmenopausal women.

It included 5,855 women (mean age 71 years) who underwent baseline dual-energy x-ray absorptiometry (DXA) scans to assess body fat and body fat composition and have been followed for 12 years.

Using information from national cancer registries, the study recorded 811 solid cancers in the women and showed that the ratio of abdominal fat to peripheral fat was a significant independent predictor of cancer diagnosis up to 12 years after baseline (hazard ratio [HR] 1.30; 95 per cent, CI: 1.11 to 1.52; p< 0.001). Neither BMI nor fat percentage showed significance.

Specifically, there were 293 breast and ovarian cancers, 345 lung and gastrointestinal (GI) cancers, and 173 other cancers. Looking in detail at specific cancers and risk factors, the investigators determined that only lung and GI cancers were associated with high abdominal-to-peripheral fat ratios (HR: 1.68; 95 per cent, CI: 1.12 to 2.53; p<0.05 and HR: 1.34; 95 per cent, CI: 1 to 1.8; p<0.05, respectively).

Additional cancer risk factors were older age, receipt of hormone replacement therapy and smoking, but after controlling for these risk factors, fat ratio remained an independent risk factor.

“The average elderly woman can very much use this information, as it is known that the menopause transition initiates a shift in body fat towards the central trunk area. Therefore, elderly women should be especially aware of their lifestyle when they approach the pre-menopause age,” said Ms Mærsk Staunstrup.

“Clinicians can additionally use the information for a preventive conversation with women who are at higher risk of cancer. While clinicians have access to whole-body DXA scanners at most hospitals, portable DXA scanners have become available on the commercial market and this may allow regional bone and fat scanning, however, it may not be the most reliable for measuring central obesity,” she concluded.

Commenting on the study, Dr Andrea De Censi from Galliera Hospital in Genova, Italy, said the study provides important confirmation on the role of obesity, and particularly insulin resistance, in the aetiology of several cancers.

“While obesity has previously been linked to cancer risk, the link to lung cancer is new and intriguing,” he commented.

“Increases in insulin, resulting from over-consumption of simple carbohydrates such as potatoes, wheat, rice and corn, result in fat accumulation that is specifically visceral and abdominal,” Dr De Censi explained. Insulin also has detrimental effects on hormone production and adipose cells in fat tissue increase chronic inflammation throughout the body — another risk factor for several cancers.

“These data open the door for clinicians to initiate a number of interventions in obese patients. In addition to fat loss with diet and exercise, there may be a potential role for a diabetes drug, such as metformin, which can lower insulin effects and contribute to cancer prevention.”

High-risk prostate cancer may benefit equally from two new treatments

Patients with high-risk prostate cancer starting long-term hormone therapy may benefit from two new treatments, according to late-breaking results from the STAMPEDE trial presented at the ESMO 2017 Congress in Madrid.

Long-term hormone therapy alone has been the standard of care for patients with high-risk, locally-advanced or metastatic prostate cancer since the 1940s.

STAMPEDE is a platform protocol using a multi-arm, multi-stage design to efficiently investigate a number of new treatments versus standard of care in patients with high-risk prostate cancer. It included men who were starting long-term hormonal therapy for the first time. The trial previously found that docetaxel improved survival compared to standard of care (hazard ratio [HR], 0.78), and that abiraterone acetate with prednisolone (AAP) also improved survival compared to the same standard of care (HR, 0.63).

First author Mr Matthew Sydes, statistician, MRC Clinical Trials Unit, University College London, UK, said: “Right now, oncologists and urologists want to know which combination is preferable, which is why we conducted this analysis.”

The analysis used prospectively-collected data from the STAMPEDE trial to directly compare patients randomised to the docetaxel and AAP research arms while both arms of the trial were recruiting. The randomisations overlapped between November 2011 and March 2013. This comparison included 566 patients, of whom 189 were randomised to receive docetaxel and 377 were randomised to receive AAP, both on top of standard of care androgen-deprivation therapy (with radiotherapy for some patients).

The estimate for the primary outcome of overall survival was a HR of 1.16, and the difference between the two treatments was not statistically significant, with confidence intervals capturing estimates favouring both AAP and docetaxel.

For the early outcome measures of failure-free survival and progression-free survival, estimates of treatment effect clearly favoured AAP, with HRs of 0.51 and 0.65, respectively. The estimates of treatment effect for late-outcome measures of freedom from metastatic progression and freedom from symptomatic skeletal events favoured AAP, but the differences between treatment groups were not statistically significant.

Mr Sydes said: “This comparison was of course underpowered, but it is the only data we have to directly compare docetaxel and abiraterone in this setting.”

Prof Nicholas D James, Chief Investigator of STAMPEDE and Consultant Oncologist at University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK, said: “The individual trials suggested that abiraterone may have a larger effect on survival than docetaxel, but this did not translate into a clear advantage in this study. Both drugs provide a survival advantage over standard of care alone in men with high-risk prostate cancer beginning long-term hormone therapy. This study suggests that starting with either drug is acceptable and choice may depend on availability.”

Commenting for ESMO, Prof Cora N Sternberg, Chief, Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy, said: “The STAMPEDE trial has a unique design and has prospectively studied more than 9,000 patients with high-risk or metastatic hormone-sensitive prostate cancer compared to the standard of care. By 2025, it will have reported the results of 10 randomised clinical trials.

“This comparison offers strong evidence for the combination of standard of care plus AAP versus standard of care alone in terms of failure-free survival and progression-free survival and less strong evidence in terms of metastases-free survival and skeletal-related events,” she continued. “There was no difference in survival with standard of care plus docetaxel, as compared to standard of care plus AAP.”

Prof Sternberg pointed out that the toxicity profiles were quite different in the two trials. The AAP results are consistent with the LATITUDE trial, which also favoured AAP over standard of care in high-risk patients.

She said: “Both STAMPEDE randomised trials support starting hormonal therapy plus either AAP or six cycles of docetaxel. At one and two years, the percentage of patients with grade 3 or 4 (severe) toxicities was low and similar between the two groups. Toxicities associated with chemotherapy for six cycles will dominate decisions about up-front docetaxel. Toxicities associated with AAP are also likely to influence decisions.

“Physicians will base their choice of therapy on availability and patient characteristics and preferences.”

Regarding the need for further studies, Prof Sternberg said: “Cardiovascular follow-up will be important in patients taking AAP. In the future, we will get data on whether patients could start with both docetaxel and novel hormonal therapy, such as AAP.

“Ongoing randomised trials in metastatic hormone-sensitive prostate cancer will evaluate the combination of novel hormonal therapy and chemotherapy up-front (ARASENS; NCT02799602), as will data from the PEACE 1 trial (NCT01957436), in which two-thirds of patients will receive AAP plus docetaxel chemotherapy for hormone-sensitive, high-risk prostate cancer.”