How the Brexit Decision Might Affect Healthcare

WebMD Health News
How the Brexit Decision Might Affect Healthcare

Peter Russell
June 24, 2016


LONDON — The world is reeling from the United Kingdom's (UK) historic vote on Thursday to leave the European Union (EU). The ramifications will be felt in all aspects of life, from economic, to travel and immigration, to national security, and not the least, to health.

The future of the UK's National Health Service (NHS) featured prominently in the run-up to yesterday's referendum, and will figure prominently in the changes brought about by the decision.

While the "Leave" camp claimed the cash that the UK currently gives to the central leadership of the EU in Brussels, Belgium could now be ploughed back into health services, the "Remain" camp warned that economic turmoil from the British Exit (Brexit) threatened the fragile finances of the NHS.

But the bell has been rung. Now that 51.9% of the UK's citizens chose to get out of the EU, while 48.1% backed remaining part of the club of 28 nations, what might the impending exit mean for the future of health and social care in the UK?

Timing

Firstly, nothing significant is going to change today or tomorrow.

Soon after the result was declared, Prime Minister David Cameron announced he would stand down in the autumn, by which time another member of the conservative party will be chosen to be the new leader in the UK.

It will be up to the next prime minister to decide when to pull the lever to leave the EU, known as Article 50 of the Lisbon Treaty, which would give the UK 2 years to negotiate withdrawal terms.

Will There Be More Cash for the NHS?

Supporters of Leave originally claimed that quitting the EU would give the UK an additional £350 million a week to spend on health and other public services.

However, an analysis this month by the Institute for Fiscal Studies (IFS) disputed this figure, saying that after taking into account money received back from the EU, the UK's net contribution was £150 million a week.

However, this takes no account of any financial turmoil that could hit government finances.

The IFS analysis predicted that Brexit will add an additional 2 years of austerity to the UK's economy. Carl Emmerson, IFS deputy director and an author of the report, said: "the overwhelming weight of analysis suggests that the economy would shrink by more than enough to offset the positive effect on the public finances of the reduced financial contribution to the EU budget."

Will Containing Immigration Cut NHS Costs?

Immigration and its effect on health and other public services was a key topic during the referendum campaign.

A recent analysis by the Nuffield Trust estimated that in 2014, migration from the EU added £160 million in additional costs for the NHS across the UK.

However, it says this was a relatively small sum when set against the £1.4 billion in additional costs caused by other factors such as treating an ageing population and migrants from outside the EU.

The report also pointed out that immigrants are taxpayers as well as patients and that they could even be making a net contribution to available resources.

Will Health Insurance Cards Still Work in the EU?

British travellers to EU and European Economic Area (EEA) countries can carry a European Health Insurance Card (EHIC) giving them the right to access state-provided healthcare on temporary stays at a reduced cost or, in many cases, for free.

But once the UK leaves the EU, and if it also left the EEA, British tourists and retirees abroad would have to cover health care costs from their own pockets or from travel insurance in these countries.

However, it is possible that the UK could negotiate specific agreements with EU and EEA countries for EHIC to remain valid.

What About the NHS Staff?

A total of 55,000 out of the 1.2 million staff in the NHS in England are citizens of other EU countries — equivalent to 5% of NHS workers.
That is close to the 4.7% of the UK population who were born in other EU countries.

According to the Nuffield Trust, 10% of physicians and 4% of nurses are from other EU countries.

The NHS's most senior physician, Sir Bruce Keogh, MD, has called on NHS leaders to send out a message to European staff working in the health service that they are valued and welcome in the wake of the referendum result. Sir Bruce told the Health Service Journal: "It is really important we make them feel welcome.

"If you are a European doctor or nurse you might not feel too welcome at the moment."

The British Medical Association (BMA) urged politicians not to play games with the UK's health services. BMA council chief, Mark Porter, MD, said in a statement: "We stand together as one profession with our colleagues from Europe and across the world, with whom we live, work and study and on whom the NHS depends."

What About Medical Research?

UK medical science has benefited from EU funding for decades.

In the wake of the result, several leading experts issued statements about what it could mean for research.

Nobel Laureate Sir Paul Nurse, PhD, director of the Francis Crick Institute, said: "This is a poor outcome for British science and so is bad for Britain.

"Science thrives on the permeability of ideas and people, and flourishes in environments that pool intelligence, minimise barriers, and are open to free exchange and collaboration.

"British scientists will have to work hard in the future to counter the isolationism of BREXIT if our science is to continue to thrive."

Professor Anne Glover, PhD, vice-principal external affairs and dean for Europe at the University of Aberdeen, said: "I am personally heartbroken and I have great concern for the future of British science, engineering and technology.

"Our success in research and resulting impact relies heavily on our ability to be a full part of European Union science arrangements and it is hard to see how they can be maintained upon a Brexit."

Could the Exit Affect Access to Medicines?

Leading figures from the life sciences industry recently expressed their fears that Brexit could jeopardise the UK's central role in the European pharmaceutical industry and call into question the country's access to innovative medicines.

Following the result, Mike Thompson, the head of the Association of the British Pharmaceutical Industry (ABPI), said in a news releases that leaving the EU would create "immediate challenges for future investment, research and jobs in our industry in the UK."

Meanwhile, the BioIndustry Association (BIA) said in a statement that "key questions about the regulation of medicine, access to the single market and talent, intellectual property and the precise nature of the future relationship of the UK are now upon us."

Before the vote, the ABPI, BIA, and business leaders and organizations for the life-sciences industry, had signed a letter warning that the UK leaving the EU would put access to cutting-edge medicines at risk, according to the ABPI release.

An early sign of the threat posed to the UK's position came as the association representing Germany's pharmaceutical industry, Beraten Analysieren Handeln, called for the European Medicines Agency (EMA), the UK's equivalent to the US Food and Drug Administration, to be relocated from its central seat in London to Bonn, Germany following the UK's departure from the EU.

Olaratumab May Cause ‘Potential Paradigm Shift’ In Soft-Tissue Sarcoma Treatment

Olaratumab May Cause ‘Potential Paradigm Shift’ In Soft-Tissue Sarcoma Treatment
Soft-tissue sarcoma patients with locally advanced or metastatic disease derive a survival benefit with the combination of olaratumab and doxorubicin

Date: 13 Jun 2016
Author: By Shreeya Nanda, Senior medwireNews Reporter
Topic: Anti-Cancer Agents & Biologic Therapy / Soft Tissue Sarcomas / Translational Research

medwireNews: The addition of olaratumab to doxorubicin improves survival in patients with locally advanced or metastatic soft-tissue sarcoma, find researchers.

Treatment with the antiplatelet-derived growth factor receptor α (PDGFRα) Monoclonal antibody prolonged progression-free survival (PFS) and furthermore led to a “highly significant” improvement of 11.8 months in median overall survival (OS), “suggesting a potential paradigm shift in the treatment of soft-tissue sarcoma”, they write in the The Lancet.

In the phase II part of this trial, 133 patients not previously treated with an anthracycline were randomly assigned to receive doxorubicin 75 mg/m2 on day 1 of a 3-week cycle either alongside intravenous olaratumab 15 mg/kg on days 1 and 8 or alone for up to eight cycles. Participants in the dual therapy arm could continue with single-agent olaratumab after completing eight doxorubicin cycles, while those in the doxorubicin alone arm could receive olaratumab monotherapy after progression.

The primary endpoint of PFS was a median of 6.6 months for the 66 olaratumab-treated patients compared with 4.1 months for the 67 given doxorubicin alone. This equated to a hazard ratio (HR) of 0.672 in favour of olaratumab plus doxorubicin, which with a p value of 0.0615 met the protocol-defined significance level of 0.1999.

Of note, median OS was 26.5 months in the olaratumab arm and 14.7 months in the control arm, and corresponded to a significant HR of 0.46.And OS was improved by olaratumab across the predefined subgroups, including histological tumour type, number of previous lines of treatment, and PDGFR status, but the difference was not always significant, reports the team led by William Tap, from Memorial Sloan Kettering Cancer Center in New York, USA.

Patients given olaratumab plus doxorubicin had a higher incidence of side effects of grade 3 or worse than those treated with doxorubicin alone, with neutropenia (53 vs 32%) and fatigue (9 vs 3%) seen more often in the dual than the single therapy arm.But the researchers point out that the incidence of febrile neutropenia was comparable (13 vs 14%) and a smaller proportion of patients in the olaratumab arm discontinued treatment as a result of an adverse event (13 vs 18%).

Writing in an accompanying piece, Winette van der Graaf, from The Institute of Cancer Research in Sutton, UK, hails the findings as promising “[i]n view of the desperate need of patients with soft-tissue sarcomas for new active drugs”.

But she says that the OS difference of nearly a year beyond the PFS gain of 2.5 months is “as much promising as puzzling”. The commentator believes that “[t]he exact effect of various post-study treatments, including local treatments, is not easy to interpret.”

“Differences in the pace of progression before start of treatment might have affected the results because no specific time period in which progression should have occurred before patients entered the study was defined and only the group with shorter history of disease showed a significant increase in overall survival”, she continues.

Winette van der Graaf asks: “[W]hy does targeting PDGFRα and its combination with doxorubicin lead to this impressive gain in overall survival?” But she acknowledges that at present this is an open question as in-depth information about PDGFR receptors in sarcomas is lacking.

References

Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 2016; Advance online publication 9 June. doi: http://dx.doi.org/10.1016/S0140-6736(16)30587-6van der Graaf WTA. Olaratumab in soft-tissue sarcomas. Lancet 2016; Advance online publication 9 June. doi: http://dx.doi.org/10.1016/S0140-6736(16)30788-7

Immune Modulation in Colorectal and Anal Cancers

Immune Modulation in Colorectal and Anal Cancers

Highlights from ASCO 2016 Annual Meeting

Date: 08 Jun 2016
Topic: Gastrointestinal cancers / Cancer Immunology and Immunotherapy
The results from studies on checkpoint inhibition for three emerging indications in colorectal and anal cancers were presented in the oral abstract session at ASCO 2016 Annual Meeting (3-7 June, Chicago, United States). The data are compelling, but do not yet change standard practice. PD-1 blockade alone or in combination with CTLA-4 inhibition in microsatellite unstable colon cancer, MEK inhibition plus PD-L1 in microsatellite stable colon cancer, and PD-1 blockade in anal squamous cell cancer warrant further investigation.

PD-1 blockade alone or with CTLA-4 blockade in MSI-H colon cancer

Although approximately 15% of early colorectal cancers (CRCs) display a high degree of microsatellite instability (MSI-H), indicating a deficient DNA mismatch repair system, MSI-H status is found in approximately 4% of metastatic CRC (mCRC). MSI-H CRC is known to have an exceptionally high mutation burden. In CRC, MSI-H is associated with increases in immune infiltration and expression of immune checkpoint regulators. Interim results from CheckMate-142, a phase II study that evaluates nivolumab or nivolumab plus ipilimumab in patients with mCRC, MSI-H and non-MSI-H were presented (1).

Increased presence of tumour-specific neoantigens in hypermutated tumours is associated with an increased quantity of tumour-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, such as programmed death-1 (PD-1) and PD-1 ligand 1 (PD-L1). Checkpoint inhibitor blockade, including PD-1 blockade and CTLA-4 blockade, is expected to be particularly effective in MSI-H CRC.

The presented results indicate that nivolumab monotherapy demonstrated encouraging activity in patients with MSI-H status at this interim analysis; the combination of nivolumab plus ipilimumab also demonstrated promising preliminary activity. Responses to nivolumab monotherapy and the nivolumab plus ipilimumab combination were durable in patients with MSI-H.

Nivolumab and the combination of nivolumab plus ipilimumab demonstrated tolerable safety profiles in relation to clinical benefit that were consistent with observations in other solid tumours.

Results are encouraging and support continued evaluation of nivolumab monotherapy and nivolumab plus ipilimumab in patients with MSI-H metastatic CRC and potentially other tumours with mismatch repair defects.

MEK inhibition plus PD-L1 in MSS colon cancer

MSI-H CRC, which is associated with deficiency in DNA mismatch repair and high mutation load demonstrates response to single agent therapy targeting PD-L1/PD-1 axis. This is consistent with the hypothesis that tumours with high mutation burden are more responsive to cancer immunotherapy. However, MSI-H CRC represents only approximately 4% of metastatic CRC. Treatments resulting in potent and durable responses remain an unmet need for patients with microsatellite stable (MSS) mCRC.

The MAP kinase pathway is one of the most frequently dysregulated pathways in cancer due to hyperactivation by growth factor receptors or activating mutations. Single agent MEK inhibition has shown little activity in mCRC. Response to PD-L1/PD-1 targeting agents in mismatch-repair proficient CRC (ie MSS) has been lower than seen in other indications.

In preclinical models, targeted inhibition of MEK leads to upregulation of MHC I on tumour cells, induces intratumoural T-cell infiltration and enhances anti-PDL1 activity. The researchers therefore conducted a phase Ib study combining cobimetinib (MEK inhibitor) and atezolizumab in patients with advanced solid tumours (2). Tumour-specific expansion cohorts, including KRAS-mutant CRC, and serial biopsy cohorts in solid tumours were opened.

Cobimetinib plus atezolizumab was well tolerated at the maximum administered doses in patients with chemorefractory KRAS mutant mCRC. The combination resulted in a higher clinical response rate in MSS patients than expected from either cobimetinib or atezolizumab alone. The overall response rate (ORR) of 17% and 6-month overall survival (OS) of 72% represent clinical improvements over a historical 1% of ORR and approximately 6-month median survival for standard of care in this setting.

These results suggest that cobimetinib can sensitise tumours to atezolizumab by increasing MHC I expression on tumour cells and promoting intratumoural CD8 T cell accumulation.

Based on these encouraging preliminary results, the expansion of this phase Ib study is ongoing in mCRC.

PD-1 blockade in anal squamous cell cancer

Over 27,000 new cases annually of anal cancer are diagnosed worldwide. The incidence of anal cancer continues to rise annually. There is no established standard of care for patients with refractory metastatic anal squamous cell cancer. To date, a prospective phase II clinical trial has not been completed for patients in metastatic setting.

Aproximately 80-95% of cases are linked to human papillomavirus (HPV). The role of HPV in the tumourigenesis of this cancer type provides rationale for the use of immune checkpoint blockade agents as a novel therapy for treatment of patients with a virally driven disease.

The researchers presented at ASCO 2016 the results from the first prospective phase II study to be completed in metastatic refractory anal squamous cell cancer (3). Single agent nivolumab was well tolerated and fulfilled the primary endpoint of response. No additional unexpected serious adverse events in HIV-positive patients were observed. Rapid enrolment was feasible. Continued clinical trial enrollment is crucial in the hopes of obtaining an FDA indication for the “rare” cancer of metastatic squamous cell carcinoma of the anal canal.

Additional updated cfDNA data will be presented at the ESMO World Congress on Gastrointestinal Cancer, (29 June – 2 July 2016, Barcelona, Spain).

References

Overman MJ, Kopetz S, McDermott RS, et al. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results. J Clin Oncol 34, 2016 (suppl; abstr 3501)
Bendell JC, Kim TW, Goh BC, et al. Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC). J Clin Oncol 34, 2016 (suppl; abstr 3502)
Morris VK, Ciombor KK, Salem MS, et al. NCI9673: A multi-institutional eETCTN phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal (SCCA). J Clin Oncol 34, 2016 (suppl; abstr 3503)

10-Year Adjuvant AI Use Supported In Hormone Receptor-Positive Early Breast Cancer

10-Year Adjuvant AI Use Supported In Hormone Receptor-Positive Early Breast Cancer

Extended treatment with letrozole improves outcomes relative to placebo after 5 years of letrozole in postmenopausal women with early breast cancer

Date: 06 Jun 2016
Author: By Shreeya Nanda, Senior medwireNews Reporter
Topic: Anti-Cancer Agents & Biologic Therapy / Breast Cancer, Early Stage
medwireNews:

Postmenopausal women with hormone receptor-positive early breast cancer who have taken an aromatase inhibitor (AI) as adjuvant therapy for around 5 years can benefit from extending treatment for a further 5 years, suggest the results of a placebo-controlled trial.

The researchers report improvements in disease-free survival (DFS) and incidence of contralateral breast cancer with the AI letrozole, but overall survival (OS) was not prolonged compared with placebo.

The MA.17R trial recruited 1918 postmenopausal women who had previously received adjuvant AI therapy for a median of 5 years and randomly assigned them to receive either letrozole 2.5 mg/day or placebo for another 5 years.

Extended treatment with letrozole significantly reduced the risk of disease recurrence or occurrence of contralateral breast cancer by 34% compared with placebo. The 5-year DFS rate was 95% for the 959-letrozole treated patients and 91% for the 959 women given placebo.

The annual incidence of contralateral breast cancer was also significantly lower with letrozole than placebo, with rates of 0.21% versus 0.49% per year, giving a hazard ratio of 0.42.

However, after a median follow-up of 6.3 years, the 5-year OS rates were comparable between the treatment arms, a finding that the authors of a linked editorial do not find surprising.

Rowan Chlebowski and Matthew Budoff, both from Harbor–UCLA Medical Center in Torrance, California, USA, write: “The participants, who in most cases underwent randomization approximately 10 years after the time of diagnosis, have passed the peak risk of recurrence and a considerable proportion of their remaining risk as well.

“In any event, avoiding a new diagnosis of invasive breast cancer is a benefit in itself.”

Researcher Paul Goss, from Massachusetts General Hospital Cancer Center in Boston, USA, and colleagues found a significant increase in bone-related adverse events in the letrozole group relative to the placebo group, with significantly higher incidence of bone pain (18 vs 14%), fracture (14 vs 9%) and new-onset osteoporosis (11 vs 6%).

The arms were comparable with respect to the incidence of other toxicities, except for increase in alkaline phosphatase and alanine aminotransferase levels.

The team believes that “[u]ltimately, the decision of whether a patient should receive prolonged therapy with an aromatase inhibitor will depend largely on the extent of its effect on her in terms of toxic effects and quality of life, the extent to which bone mineral density is maintained, as indicated by sequential scans, and the patient’s individual risk of disease recurrence.”

The research was simultaneously published in The New England Journal of Medicine and presented at the annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA.

References

Goss PE, Ingle JN, Pritchard NJ, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 2016; Advance online publication 5 June. doi: 10.1056/NEJMoa1604700

Chlebowski RT, Budoff MJ. Changing adjuvant breast cancer therapy with a signal for prevention. N Engl J Med 2016; Advance online publication 5 June. doi: 10.1056/NEJMe1606031