MADRID’S stunning boulevards and awe-inspiring galleries and museums were a sorely-missed backdrop for this year’s European Society for Medical Oncology (ESMO) Virtual Congress 2020. Once home to Nobel laureate Severo Ochoa, jointly awarded the prize in 1959 for his discovery of the mechanisms of synthesis of RNA and DNA, the beautiful city was unable to host this year’s congress because of the ongoing impact of the coronavirus disease (COVID-19) pandemic. Undaunted, >30,000 people from 150 countries formed a community online for a virtual ESMO 2020. Despite the limitations and separations of a global pandemic, the new digital format massively increased education and access for oncologists and cancer care professionals worldwide, as 49,000 hours of streamed content were watched over the 3-day science weekend.
The digital format was certainly apt for the theme of ESMO 2020: ‘bringing innovation to cancer patients’. In her Presidential Address at the Opening Ceremony, Prof Solange Peters, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, highlighted the innovation of the oncology field and medical community in ensuring ongoing care during the challenges of a pandemic: “It makes me proud to see how we, as a society, have been able to innovate and implement new ways of working to continue serving the global oncology community.” She underscored the importance of continuing medical education and collaborative research meetings, despite the difficulties of this year: “This event is, and remains, the most prestigious platform in Europe on which to share the latest oncology science. We owe it to our patients to uphold this annual meeting and continue driving therapeutic progress in our field.”
With the impact of the COVID-19 pandemic at the forefront of most healthcare provisions for 2020, the ESMO 2020 community was provided with a direct update by world-leading infectious diseases expert Dr Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA, in his Keynote Lecture at the Opening Ceremony. The impact of COVID-19 on patients with cancer was further considered in expert panel-led sessions at the congress, with the most fascinating insights summarised in our congress review ‘COVID-19: Impact on Cancer Patients and Oncology Professionals’.
Beyond COVID-19, the congress was packed with clinical insights, late-breaking data, and scientific discoveries across cancer care, new therapeutics, and the oncology profession. Notable findings shared at the congress are highlighted in the following pages of our review, including results supporting a new first-line treatment for metastatic kidney cancer, insights assessing the benefit of radiotherapy in non-small cell lung cancer, and evidence for the survival benefit of immunotherapy in gastric and oesophageal cancers. The toll of the COVID-19 pandemic on oncologists’ wellbeing and provision of cancer care for patients was also studied and is summarised in our review, along with an analysis comparing healthcare spending on cancer across Europe.
Honouring the work of field-leading oncologists, the annual ESMO awards were announced ahead of the congress. Prof Hans-Joachim Schmoll, University Clinic of Martin Luther University, Halle, Germany, received the ESMO Award 2020 for his work in developing the speciality of medical oncology both in Germany and internationally, and particularly in developing treatment standards and progressing medical education. The ESMO Lifetime Achievement Award 2020 was presented to Prof Nadia Harbeck, University Hospital of Ludwig-Maximilians-University (LMU), Munich, Germany, for her work throughout her career to advance global cancer research in both supporting the development of evidence-based guidelines and in her groundbreaking research in individualising the care of patients with breast cancer. Prof Harbeck commented: “To receive this award as a gynaecologist who has spent her career individualising treatment for early breast cancer shows that ESMO is a truly interdisciplinary society.”
This interdisciplinary, collegiate atmosphere was palpable throughout the congress. During the congress, the parallel European Oncology Nursing Society (EONS) highlighted clinical and research findings alongside practical considerations for the care of cancer patients and progress of oncology nursing. Insights shared throughout ESMO 2020 at proffered paper sessions, keynote lectures, colloquia, and patient advocacy sessions spanned basic science, population studies, clinical research, and healthcare policy in Europe and globally. Attendees shared in the community of the congress online, with breaking research news debated on Twitter, alongside shared photographs of oncologists and researchers tuning in to the congress from their homes and hospitals around the world.
Prof Peters celebrated the value of this education-driven community, at the congress and beyond, to further cancer care globally: “ESMO firmly believes in a world where cancer professionals grow together as a community; a community that fosters inclusion across disciplines, draws strength from people’s differences, and blurs geographical borders.” With field-changing innovation and research findings shared at ESMO 2020, and the fires of collaborative education and progress stoked during the meeting, we look forward to the year ahead in oncology and to sharing in ESMO 2021, planned for Paris, France in September.
Metastatic Kidney Cancer: New First-Line Treatment
RESULTS from the Phase III CheckMate 9ER trial have provided hope for patients with metastatic kidney cancer as the new first-line treatment trial has shown success. This was reported in a press release dated 19th September 2020 at the ESMO Virtual Congress 2020.
A combination of the drugs nivolumab and cabozantinib, both used as monotherapies in the second line, were compared in the trial to the standard of care, first-line treatment, sunitinib. The combination showed superiority to sunitinib for progression-free survival, overall survival, and response rate, and there were consistent benefits in subgroups of age, sex, PD-L1 expression, bone metastases, International Metastatic RCC Database Consortium (IMDC) risk group, and geographical region.
Dr Toni Choueiri of Harvard Medical School, Boston, Massachusetts, USA, and author of the study, summarised the findings: “The results with combination therapy were statistically significant and clinically meaningful. The risk of progression or death was cut by almost 50%, death was cut by 40%, and the response rate doubled. This will become an important treatment option to choose from.”
Adverse events were reported in the combination arm, with >50% of patients in this group requiring a dose reduction. However, only 3% had to stop taking the combination therapy because of toxicity, compared to 9% in the sunitinib arm.
Dr Dominik Berthold, Lausanne University Hospital, Lausanne, Switzerland, expressed his belief that the combination treatment must now be considered as a new first-line option. Although, he did caution that longer-term data is needed for CheckMate 9ER: “The 18 months of follow-up is still quite short. The question is whether the responses to treatment are durable or if patients progress at some point.”
Next, Dr Berthold suggests that it would be useful to know whether the combination treatment would be effective in non-clear cell carcinoma, as these patients were excluded from the trial.
COVID-19 Pandemic Halts Cancer Care and Damages Oncologists’ Wellbeing
DELAYS and cancellations of cancer treatment have been implemented worldwide in order to protect vulnerable patients from exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, it has led to a backlog of care and research at a time when oncologists are facing burnout. This is according to studies discussed in a press release at the ESMO Virtual Congress 2020 dated 14th September 2020.
Early on this year, before the pandemic, the European Cancer Information System (ECIS) estimated that the number of new cancer cases in Europe would reach 2.7 million this year, alongside 1.3 million deaths. Dr Stefan Zimmermann, ESMO Press Officer, stated that coronavirus disease (COVID-19) may not be the only factor that has put a strain on the oncology specialty: “The pandemic has also revealed some weaknesses in how cancer care is resourced and organised.”
A study conducted by researchers at the Centre Hospitalier Universitaire Sart Tilman, Liège, Belgium, looked at oncology centres in 18 countries to assess the extent to which COVID-19 has challenged the management and delivery of cancer care. Study author Dr Guy Jerusalem expressed his worries about the impact of the pandemic: “There is a risk that the diagnosis of new cancer cases will be delayed and that more patients will be diagnosed at a later stage of their disease.”
Results of the study showed that surgery was the treatment most likely to have been cancelled (in 44.1% of centres), followed by chemotherapy (25.7%) and radiotherapy (13.7%).
Another study, conducted by the ESMO Resilience Task Force, used online surveys to assess the impact of the pandemic on 1,520 oncology professionals from 101 countries. More than one-third said they had experienced feelings of burnout, one-quarter were at risk of distress, and two-thirds said they were unable to perform their roles as well as they could prior to the pandemic.
The ESMO Resilience Task Force will now look into developing more specific interventions to further help and support oncology professionals during and beyond the pandemic, as well as doing all they can to avoid delays to any treatment that may impact patient survival.
Gastric and Oesophageal Cancers Benefit from Immunotherapy
THREE studies, the results of which were presented on 21st September 2020 at the ESMO Virtual Congress 2020, have provided evidence that immunotherapy is beneficial for patients with gastric and oesophageal cancers. The studies analysed different patient populations and different immune checkpoint inhibitors, which are currently not approved for early therapy in Western countries, showing that immunotherapy has potential as first-line therapy in these patient populations who currently have poor survival.
Firstly, the CheckMate 649 trial compared nivolumab plus chemotherapy to chemotherapy alone as first-line treatment in patients with non-HER-2-positive advanced gastric cancer, gastro-oesophageal junction cancer, or oesophageal cancer (all had adenocarcinoma histology). Overall survival and progression-free survival were significantly improved in patients with PD-L1 combined positive score (CPS) >5 and >1 tumours in the nivolumab plus chemotherapy group.
Prof Salah-Eddin Al-Batran, ESMO 2020 Upper Gastrointestinal Tract Chair, commented on the data: “The results are clinically very relevant. The open question is the effect in patients who have a PD-L1 CPS <5.”
The second trial, ATTRACTION 4, was similar to CheckMate 649 except that it was exclusively performed in patients of Asian ethnicity and the primary endpoints were designed for all-comers, rather than a specific CPS value. Again, the first-line treatment with nivolumab plus chemotherapy improved the progression-free survival, though not overall survival. Prof Al-Batran provided a possible explanation for this: “Overall survival was not improved, possibly because all-comers were treated or because patients in Asia receive more subsequent therapies than Western populations.”
Finally, the KEYNOTE 590 trial evaluated first-line chemotherapy with or without pembrolizumab in patients with squamous cell carcinoma of the oesophagus, adenocarcinoma of the oesophagus, or Siewert Type 1 gastro-oesophageal junction adenocarcinoma. Results showed improvements in both progression-free survival and overall survival for patients with squamous cell carcinoma of the oesophagus with PD-L1 CPS >10 tumours, all squamous cell carcinomas, all patients with CPS >10, and the study population as a whole.
Prof Al-Batran concluded: “The results of these trials offer oncologists new treatment options. In the first-line setting, there is a clear change of our standard of care.”
Routine Radiotherapy Does Not Improve Survival in NSCLC
RADIOTHERAPY treatment following surgical resection and (neo)adjuvant chemotherapy may not be required in non-small cell lung cancer (NSCLC). The authors of the French study, which included 501 patients, highlighted their findings in a press release from ESMO 2020 dated 19th September 2020.
Post-operative radiotherapy (PORT) for patients with mediastinal involvement of their NSCLC has been an area of clinical debate since a 1998 meta-analysis doubted the benefit of the practice. Improved patient selection practices and improvements in both (neo)adjuvant chemotherapy and radiotherapy have been thought to have improved the impact of radiotherapy in these patients since this 1998 study. However, the results of a French randomised controlled trial suggest otherwise.
An intention-to-treat analysis of 501 patients was conducted; 252 patients received PORT over 5 weeks and 249 received no PORT (control arm). There was no statistically significant difference in disease-free survival: 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio: 0.85; 95% confidence interval [CI]: 0.67–1.07; p=0.16). There was also no significant difference in overall survival at 3 years: 66.5% of the PORT arm (95% CI: 59–73) compared to 68.5% of the control arm (95% CI: 61–75).
Study author Dr Cécile Le Pechoux, Institut Gustave Roussy, Paris, France, highlighted the need for further analysis to determine whether there are subsets of patients that may benefit from radiotherapy: “PORT cannot be recommended for all patients with Stage II and III NSCLC with mediastinal nodal involvement. Possibly, however, for some patients it might be useful because it does decrease the rate of mediastinal relapse by 50%. This must be put into balance with the risk of over-added cardiopulmonary toxicity.”
Prof Rafal Dziadziuszko, Medical University of Gdansk, Poland, commented on the clinical insights of these findings: “This will change the practice of many institutions that adopted standard use of radiotherapy in these patients. We can safely say there is no net benefit from such treatment but there is also potential harm, which we see from this study, so any potential benefits in some patients are offset by the predominantly higher risk of cardiopulmonary toxicities.”
Asymmetry in Healthcare Spending on Cancer in European Countries Revealed
DISPARITIES in healthcare spending and unequal access to clinical trials across European countries has led to limitations to cancer medicine in the continent. This is according to the results of a new study presented as part of a press release at ESMO 2020 on 18th September 2020.
A clinical trial analysis has shown that patients with cancer living in Western Europe may have greater access to new treatments because countries in this part of the continent run more trials than countries in Eastern and Central Europe. The study indicated large differences in access to new treatments and therapies in development for these different population groups. Dr Teresa Amaral, study co-author from University Hospital Tübingen, Tübingen, Germany, reinforced the results of the investigation: “Our study gives us proof of what we previously suspected, that there is a huge asymmetry in the number of clinical trials for cancer treatments in different countries.”
The clinicaltrials.gov database was used to search for trials in adults with tumours between 2009 and 2019 in 34 countries. The search revealed that Albania had the fewest active interventional clinical trials and Belgium had the most. Patients with cancer who had more access to clinical trials are likely to benefit from this because they can access novel therapies during earlier phases and may not have to wait for licensing and reimbursement. “Also, all trial participants benefit from the regular follow-up and monitoring involved in taking part in a clinical study,” said Dr Amaral.
Also reported at ESMO 2020 were the results of a health economics analysis that showed that ‘wealthier’ European countries spent 10 times as much as poorer countries per inhabitant on cancer medicines in 2018, comparable to the trend seen for clinical trials. Cancer-specific health spending was shown to be highest in Austria, Germany, and Switzerland, and lowest in the Czech Republic, Latvia, and Poland.
Researchers speculated that the asymmetry between countries was primarily to do with the countries’ economic strength rather than the burden of the disease. The differences in spending can be attributed to two main factors: “One is shortage of money and the other is drugs not being approved for use by some healthcare systems,” according to Dr Nils Wilking, from the Karolinska Instituet, Stockholm, Sweden. The authors of the clinical trial analysis are currently exploring the reasons for different healthcare spending in European countries to provide prospective solutions to this disparity.
Breast Cancer Recurrence Risk Reduced by Abemaciclib Adjunct Therapy
RECURRENCE of cancer is a significant concern for patients with high-risk hormone receptor positive (HR+) breast cancer. According to results from a study presented at ESMO 2020 and in a press release dated 20th September, the risk of cancer recurrence can be reduced by 25% by adding abemaciclib to hormonal therapy in patients with high-risk early HR+ human epidermal growth factor receptor 2 negative (HER2-) breast cancer.
Developments in pharmacotherapy for HR+ breast cancer have markedly improved over the last years, with many therapies now being curative for patients. However, a significant proportion (20%) of these patients have high-risk disease and thus will develop a recurrence within the first 10 years of treatment. Given the transformative introduction of CDK4/6 inhibitors, such as abemaciclib, into the treatment landscape for metastatic breast cancer, researchers set out to determine if the addition of abemaciclib to hormone treatment could reduce the risk of cancer recurrence in patients with high-risk early breast cancer.
Patients included in the randomised, open-label Phase III study (N=5,637) had HR+ HER2- early breast cancer and were at high risk for relapse, as determined by the presence of clinical and pathological risk factors. Following the completion of their primary treatment, participants were randomised to receive either abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy or endocrine therapy alone. Results showed that recurrence of cancer during this 2-year period occurred in 11.3% of patients on hormone therapy alone and in 7.8% of those with add-on abemaciclib, meaning a 25.3% reduction in risk of recurrence. Adverse effects of abemaciclib caused the discontinuation of treatment in 463 (16.6%) of patients, which mainly comprised diarrhoea. Prof Giuseppe Curigliano, University of Milan, Italy, and Chair of the ESMO Guidelines Committee, commented that: “Adherence to treatment will be an important issue to be considered in the real-life population of patients when this treatment is approved and used in clinical practice.”
Commenting on the clinical impact of the results, lead author of the study Prof Stephen Johnston, Royal Marsden Hospital NHS Foundation Trust, London, UK, said: “This is a very important trial and the findings will change practice. Once approved for high risk HR+ HER2- early breast cancer, the new standard of care for these patients will be to add 2 years of abemaciclib to endocrine therapy.”