Download kidney cancer: a spotlight on the challenges

KIDNEY
CANCER:
A SPOTLIGHT
ON THE
CHALLENGES
This report was researched and authored solely by
Bristol-Myers Squibb. Its findings are endorsed by
Kidney Cancer UK.
Date of Prep: May 2016.
Job bag number: ONCUK1600557-01.
2
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
SUMMARY
7th
Approximately 11,900 people in the UK are
diagnosed with kidney cancer every year, making
it the 7th most common cancer.2 Incidence is
increasing and mortality remains high for those
diagnosed with advanced or metastatic disease.2,3
However, it is a low political priority.4,5
Kidney cancer patients in the UK have historically
had poorer survival outcomes compared to their
European counterparts, coupled with more restrictive
access to systemic therapies.11, 24 NICE currently
approves just three medicines for the treatment of
the disease, compared to the eight recommended by
the European Society for Medical Oncology.18,19,20
According to NHS data, on average approximately
a quarter of those patients with metastatic disease
received more than one line of treatment.7 This is
despite evidence which demonstrates overall survival
is significantly greater in those patients that receive
two or more lines of therapy.8
The incidence of RCC, as well as three year survival
rates, also demonstrates stark variations across the
UK, indicating that some patients may be receiving
sub-standard care.7
Patients with ‘red flags’ for kidney cancer are still
waiting too long for a diagnosis. Many patients
reported waits of over three months.12
299
Time to treatment in kidney cancer continues to
demonstrate stark variation, ranging from an average of
just 1 day to a total of 299 days across CCGs.7
Experience of care remains poor for many patients
with kidney cancer, despite ongoing efforts by the
Government to improve this. Insufficient information
at the time of diagnosis was reported as was a lack of
access to a Clinical Nurse Specialist.12
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
INTRODUCTION
Renal cell carcinoma (RCC) is the most common form of kidney
cancer, affecting approximately 90 per cent of patients with
the kidney cancer.1 Approximately 11,900 people in the UK
are diagnosed with kidney cancer every year, making it the 7th
most common cancer.2 For patients diagnosed with early stage
disease, RCC can be completely curable with the vast majority
living for five years or more.3 However, it is predicted that almost
2,400 patients will be diagnosed with advanced or metastatic
disease every year and that approximately just a quarter of these
patients will survive for more than 12 months.4,3 Furthermore,
incidence in the UK is rising, making kidney cancer a growing
health concern.2 However, unlike more common cancers, (e.g.
breast, lung and skin), kidney cancer is not highlighted in key
policy documents.5,6
This report presents an overview of the challenges that must
be addressed, if the UK wishes to improve outcomes for those
affected by RCC.
OUTLOOK AND SURVIVAL
Incidence of kidney cancer in the UK is rising and over the last
decade rates have increased by almost two-fifths.2 In addition,
incidence rates demonstrate stark variations. A recent analysis
of 2012/13 data from the Health and Social Care Information
Centre (HSCIC) found a seven-fold variation in incidence, with
rates ranging from 3.8 to 29.2 per 100,000 across Clinical
Commissioning Groups (CCGs).7 According to data recorded
in Hospital Episode Statistics (HES), the variation in survival
is equally dramatic with three-year survival reported to be as
high as 100 per cent in some areas and as low as 24 per cent
in others.7
Survival rates for kidney cancer in the UK are improving, and half
of people diagnosed with the disease are now likely to survive for
at least ten years, however, prognosis remains heavily dependent
on the stage of disease at diagnosis.2,3 Approximately 27 per cent
of patients are diagnosed with either advanced or metastatic
kidney cancer and just one in four of these patients will survive for
more than one year.3,4 Furthermore, an additional 20-30 per cent
of patients diagnosed with more localised variants of RCC will
eventually relapse with advanced or metastatic disease.8 Recent
data from the US has found that the outlook for these patients is
also poor, with a median survival of less than two years.9
KIDNEY CANCER EUROPEAN AGE STANDARDISED INCIDENCE RATES, GREAT BRITAIN, 1979-2012
RATE PER 100,000
32
24
16
8
0
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
2007
2009
2011
YEAR OF DIAGNOSIS
MALE
FEMALE
PERSONS
Figure adapted from data published by Cancer Research UK4
THE SURVIVAL RATE OF KIDNEY CANCER PATIENTS
PERCENTAGE OBSERVED
S URVIVAL, CUMULATI VE
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0
1 – <2 Yr
2 – <3 Yr
3 – <4 Yr
4 – <5 Yr
YEAR AFTER D IAGNOSIS
UK
FRANCE
GERMANY
SWEDEN
SPAIN
Figure adapted from latest available data published by EUROCARE 5 (2000-2007)11
3
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
The UK lags significantly behind other countries with similar
health systems and wealth in relation to cancer survival,
including in RCC.10,11
Survival rates can differ across countries for a number of
reasons, including cancer awareness and referral pathways.
However, persistent differences in cancer survival rates may
represent avoidable deaths.10 Despite ongoing government
initiatives5,6 and attention focused on this area in recent years,
the UK’s performance in terms of cancer care is mixed, with
plenty of room for improvement.
Data from a recent patient survey (n=67) conducted by Kidney
Cancer UK (KCUK) (formerly the James Whale Fund for Kidney
Cancer) found that over a fifth of patients (22.0%) had stage IV
disease at the time of diagnosis,12 which is in line with the incidence
figure quoted above. In addition, of those who presented to their
GP after feeling unwell, four in ten (42.3%) of patients waited
more than three months for a diagnosis.12 This is perhaps one of
the clearest indicators that the current system for symptomatic
patients, which relies on timely referral from primary care and
prompt diagnosis within secondary care, is failing many.
Current treatments for RCC are often associated with severe
side-effects, and first-line systemic therapies are only currently
recommended by NICE for use in patients with an Eastern
Cooperative Oncology Group (ECOG) performance status
of zero or one.13,14,15 Metastatic RCC (mRCC) is generally
associated with poor prognosis and, with average survival of
less than one year for these patients, delays at any point in the
pathway, be that referral or diagnosis, may affect eligibility for
treatment which could impact survival rates.16,3,5,17
ACCESS TO TREATMENT
There are still a number of difficulties to improving the
management of RCC across the UK.
As of January 2016, seven targeted therapies have been
approved by regulatory agencies as treatments, and the
European Society of Medical Oncology’s Clinical Practical
Guidelines in RCC recommends a total of eight therapies for
the management and treatment of the disease.18,19 By contrast
the HTA body, NICE, has approved just three therapies (two
first-line and one second-line) for the treatment of advanced
and metastatic RCC in the last decade, limiting reimbursement
options for other licenced therapies.20 This has been further
exacerbated for patients in England following the removal of one
of the few therapies funded for third-line via the Cancer Drugs
Fund.21 There therefore remains a significant unmet need in the
management and treatment of the disease in the UK.
Even where reimbursement is available, analysis of Hospital
Episode Statistics (HES) demonstrates that across CCGs just a
quarter of those patients with metastatic disease received more
than one line of treatment.7 This is in spite of international research,
which indicates that the median overall survival for mRCC patients
who received two or more lines of therapy can be as much as three
times longer than those receiving just one NICE approved first-line
treatment.8 This has also been confirmed via real-world data from
the UK, where overall survival was found to be significantly greater
in those mRCC patients who received a second-line therapy (n=81)
compared to patients who received a single systemic treatment
(n=514) - 33.0months versus 20.9months, p=0.008.22
One potential method for improving outcomes in mRCC
could be to adopt international best practice and produce
NHS guidelines which are more closely aligned to those of our
European counterparts.
UPTAKE OF THERAPIES
The UK has historically had a reputation for the slow uptake of
medical innovations, including new therapies, compared to many
other countries.23 Data from 2012-2013 data found that for
innovative cancer medicines, uptake in the UK ranked 9th out
of 13 countries, behind France, Switzerland, Germany, Norway,
Sweden and Austria.23 Examining the sales data of therapies
used in the treatment of kidney cancer, indicates this reputation
may also to hold true in RCC.24
Sales data for pharmaceutical therapies are considered to be a
reliable marker of uptake. An analysis of these figures between
the UK and four other major European countries found that the
usage of systemic therapies for the treatment of RCC in the UK
was often lower, and that uptake of the treatment was slower.24
This may indicate that UK patients were less able to access these
treatments in comparison to their European counterparts.
CASE STUDIES 24
CASE STUDY A
Following the marketing authorisation of sunitinib for RCC in 200618, uptake in the UK was well below that of any other EU five
country. Use of the treatment continued to remain low in comparison even with the publication of NICE guidance in 2009, which
recommended the treatment as a cost-effective option for patients with advanced RCC.14
SUNITINIB UPTAKE (TOTAL SALES) BETWEEN 2006 AND 2014 (£ MILLIONS)
UK NICE Approval
400
360
320
MILLIONS (£)
4
280
240
200
160
120
80
40
0
2006
2007
2008
2009
2010
2011
2012
2013
2014
YEAR
UK
UK LOWER
UK UPPER
FRANCE
GERMANY
ITALY
SPAIN
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
CASE STUDY B
In 2010, pazopanib was also licensed in Europe for the first-line treatment of RCC.18 Uptake in the UK was more comparable to
the other EU five countries with the exception of Germany. This may have been aided by a positive NICE approval after just over
eight months of licensing.15
PAZOPANIB UPTAKE (TOTAL SALES) BETWEEN 2010 AND 2014 (£ MILLIONS)
200
UK NICE Approval
180
M ILLION S (£ )
160
140
120
100
80
60
40
20
0
2010
2011
2012
2013
2014
YEAR
UK
UK LOWER
UK UPPER
FRANCE
GERMANY
ITALY
SPAIN
CASE STUDY C
Axitinib was licenced in 2012 as a second-line therapy in advanced RCC for those patients whose disease had failed to
respond or progressed following first-line treatment.18,25 Available through the Cancer Drugs Fund in 2013,26 uptake of
axitinib was initially slow in the UK compared to France and Germany.
AXITINIB UPTAKE (TOTAL SALES) BETWEEN 2011 AND 2014 (£ MILLIONS)
Acceptance onto CDF
100
90
MIL LI ONS (£)
80
70
60
50
40
30
20
10
0
2011
2012
2013
2014
YEAR
UK
UK LOWER
UK UPPER
FRANCE
GERMANY
ITALY
SPAIN
Case studies A, B, and C show total yearly sales up to 2014 (full year data for 2015 was not available at time of analysis) and do
not take into account any price differential between countries as it is assumed that the price for a given drug between countries in
GBP is similar. To compensate for this assumtpion, sensitivity bands of 75% and 125% have been set for UK data. This illustrates
that even in the unlikely situation that the sale price in other countries is 25% lower than in the UK, the trend in total sales between
UK and the other EU countires is not fundamentally altered.
5
6
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
TIME TO TREATMENT
Time to treatment, the time elapsed between the first
presentation with a diagnosis of kidney cancer and the
first record of receiving chemotherapy, can affect survival
outcomes and is the subject of significant regional variation
across CCGs.7,17
Examination of Hospital Episode Statistics (HES) data for
patients diagnosed in 2014/15 who also received treatment
within the same financial year, found that across England
the average time to treatment for patients diagnosed with
mRCC was 82 days.7 This figure varied across CCGs from
just 1 day to a total of 299 days and in 80 per cent of CCGs
exceeded the 31 day maximum wait target recommended by
the Independent Cancer Taskforce and NHS England.6,7,27
It is well documented that delays to cancer treatment can
have an impact on survival outcomes.28 Examining the 20
CCGs with shortest average time to treatment (range 1-31
days) compared to the 20 CCGs with the longest (range 127299 days), the data found that in those CCGs belonging the
shortest time to treatment category, patients had an average
3-year-survival almost 10 per cent higher than those with
the longest time to treatment (65.0% versus 56.4%).7 Such
extreme variation across the country should be viewed as
a major concern by policy-makers and patients alike, and is
especially concerning given the short survival expectation of
these patients.16 The delays may also be evidence that many
diagnosed with metastatic kidney cancer could be receiving
suboptimal management of their condition and this should
be addressed as a matter of urgency.
PATIENT EXPERIENCE
Health-related quality of life has become a medical outcome
for patients with RCC, particularly since there is evidence
that it can be affected by tumour response and delayed
disease progression.22 In addition, NHS England has made
it clear that patient experience should be seen as on a par
with clinical effectiveness and safety.6 However, previous
research has indicated that patients with kidney cancer often
have poor experiences of care, more so than many other
more common cancers.29
Results from the Kidney Cancer UK (KCUK)
2015 Patient Survey
Between November and December 2015, KCUK surveyed a
total of 67 patients affected by kidney cancer across the UK to
better understand the challenges faced by patients.12
Of those surveyed, a total of 50 patients knew their stage at
diagnosis and 11 were diagnosed with stage IV disease. Only
6 of these patients received a drug treatment. 19 responded
that they had been diagnosed following a GP appointment,
of which 15 stated they had a symptom consistent with
kidney cancer. 44 patients were told that they had kidney
cancer following an unrelated medical scan. The results of
the survey are presented as follows:
“My GP gave me the ultrasound findings
over the phone. I was shocked at the
result and would have preferred a
face-to-face appointment to hear this.
As it was, I felt unsupported.”
ANONYMOUS PATIENT
A lack of timely and accessible information
Providing patients with accurate, tailored, timely and
accessible information should be seen as a critical
component of high-quality cancer services.5 However, only
three quarters of patients surveyed (74.6%) knew the stage
of their cancer at diagnosis, and almost half (43.8%) said
they would have liked information about their disease.12
Furthermore, only a third (35.8%) of patients received
written information about their condition, just over a quarter
(28.4%) were referred to a telephone line, and less than one
in ten (8.96%) were provided the details of a website to refer
to for more information.12
Of greater concern, the survey also revealed over a third of
patients (37.0%) were unhappy with the way their diagnosis
was delivered, with patients stating that their diagnosis
had not been given in a sensitive manner or that it had felt
rushed.12 Almost one in five (18%) also said that they were
left confused by their diagnosis and just under one in five
(17.9%) also said they had received conflicting information
during the course of their treatment.12
Timely referral, diagnosis and treatment
Approximately 30 per cent of patients surveyed (29.7%)
were diagnosed after visiting the GP, compared with
over two-thirds (68.8%) who were diagnosed following
an unrelated medical scan.12 The vast majority (80%)
of those diagnosed following a primary care referral
were symptomatic at presentation, with many reporting
haematuria, which is considered a red flag for cancer.12,30
However, many of these patients (30.0%) still waited over
three months to receive a diagnosis.12 In addition, almost
half (44.8%) of patients surveyed who were diagnosed
incidentally, did in fact report symptoms of the disease. This
serves to emphasise the importance of patients recognising
the symptoms and seeking early medical attention.
KIDNEY CANCER: A SPOTLIGHT ON THE CHALLENGES.
As with many cancers, survival is substantially better in
those kidney cancer patients diagnosed with early stage
disease31 meaning for many, receiving an early diagnosis
can be the difference between life and death. Ensuring
that healthcare professionals are familiar with kidney
cancer and its symptoms could make an important impact
to improving survival outcomes. In addition, ensuring
patients receive a rapid referral, prompt diagnosis and
timely access to treatment can be important.5 To address
these points, NICE has published guidelines (sometimes
known as the two week referral) to ensure patients with
symptoms indicative of renal cancer receive rapid access
to specialist care.32 However, the findings of the KCUK
survey indicated that over half of patients (55.5%) who
were symptomatic upon presentation at their GP were
not immediately referred following their first visit.12 It
is therefore clear from the data presented that further
progress is needed to meet this standard.
As discussed elsewhere, firm targets are also in place
to ensure that no patient waits longer than 31 days for
treatment following the decision-to-treat, and that the
current uptake of therapies for the treatment of mRCC
is low.6,24 As stated in the Five Year Forward View, it is
not enough to improve the rates of diagnosis unless the
current variation in treatment and outcomes is also
addressed.6 Data from the survey also found that only
half (54.5%) of patients diagnosed with advanced or
metastatic disease received a first-line systemic therapy
(such as sunitinib or pazopanib) and that just one in four
received a second-line treatment (such as axitinib).12
Systemic therapies remain the mainstay of treatment for
advanced or metastatic RCC, and offer many patients the
promise of improved survival.20 However, these findings
indicate that at present, few patients are able to benefit
from this opportunity.
Overall experience of treatment
Only 60 per cent (59.7%) of patients surveyed by KCUK
responded that they felt their views were definitely taken
into account when making decisions about
their treatment.12
Clinical nurse specialists (CNSs) have previously being
identified as an important component in ensuring patients
had a positive experience of care.6,27 Despite this, over a
third (35.5%) of patients surveyed were not given the
name of a CNS to support them through their treatment
journey.12 Of those who received a systemic treatment (17
patients) this was slightly worse, with four in ten (43.8%)
not receiving this information.12
In total, 17.5% of patients surveyed responded that they
were not satisfied with the overall standard of care they
received throughout their treatment.12 While this should
be viewed positively, it is evident that there is still much
to be done to improve the patient experience throughout
the patient pathway, especially in the case of advanced or
metastatic disease where rapid referral and timely access
to treatment is key.
1Kidney Cancer UK. What is Kidney Cancer, http://www.kcuk.org.uk/kidneycancer/what-iskidney-cancer/. Accessed March 2016
2Cancer Research UK. Kidney cancer incidence. http://www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancer-type/kidney-cancer#heading-Zero
Accessed March 2016
3Cancer Research UK. Kidney cancer survival by stage at diagnosis. http://www.
cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/
kidney-cancer/survival Accessed Jan 2016
4 Cancer Research UK. Kidney cancer incidence statistics. http://www. cancerresearchuk.
org/health-professional/cancer-statistics/statistics-by-cancer-type/kidneycancer/
incidence#heading-Three Accessed March 2016
5Department of Health. Improving Outcomes: A Strategy for Cancer, 2011. https://www.gov.
uk/government/uploads/system/uploads/attachment_data/file/213785/dh_123394.pdf
Accessed Feb 2016
6NHS England. Achieving World-Class Cancer Outcomes: A Strategy for England 2015-2020.
https://www.cancerresearchuk.org/sites/default/files/achieving_world-class_cancer_
outcomes_-_a_strategy_for_england_2015-2020.pdf Accessed Jan 2016
7Hospital Episode Statistic Data, Health and Social Care Information Centre. Data is provided
under licence via Harvey Walsh Ltd. Extracted Feb 2016. *HES covers all activity that is
covered by payment by results, but excludes community, primary care and homecare and
thus may under represent the actual activity across all care settings.
8.Harrison et al. Real-world outcomes in metastatic renal cell carcinoma: insights from a joint
community-academic registry. Journal of Oncology Practice, 2014, 10(2): e63-e72
9Manola, J. et al. Prognostic model for survival in patients with metastatic renal cell
carcinoma: results from the international kidney cancer working group. Clin Cancer Res,
2011, 17(16): 5443–5450.
10Coleman et al. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK,
1995–2007 (the International Cancer Benchmarking Partnership): an analysis of populationbased cancer registry data. The Lancet, 2011, 377(9760): 127–138.
11EUROCARE 5 database https://w3.iss.it/site/EU5Results/forms/SA0007.aspx Accessed
Aug2015
12 KIDNEY CANCER UK PATIENT SURVEY DATA
13Thompson, D. Kidney Cancer Treatment Side Effects. http://www.everydayhealth.com/
kidney-cancer/kidney-cancer-treatment-side-effects.aspx. Accessed Jan 2016
14 N
ICE. Sunitinib for the first-line treatment of advance and/or metastatic renal cell carcinoma.
http://www.nice.org.uk/guidance/TA169/chapter/1-Guidance Accessed Jan 2016
15NICE. Pazopanib for the first-line treatment of advanced renal cell carcinoma. https://www.
nice.org.uk/guidance/ta215/chapter/1-Guidance Accessed Jan 2016
16 C
ella, D. Beyond traditional Outcomes: Improving Quality of Life in Patients with Renal Cell
Carcinoma. The Oncologist, 2011, 16(2): 23-31
17 Q
uality Watch. Focus on: international comparisons of healthcare quality. www.qualitywatch.
org.uk/sites/files/qualitywatch/field/field_document/QualityWatch_International_
comparisons_full_report.pdf Accessed Aug 2015.
18European Medicines Agency. European Public Assessment Report, Renal Cell Carcinoma.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.
jsp&mid=WC0b01ac0 58001d124 Accessed Jan 2016
19ESMO. Clinical Practice Guidelines: Renal Cell Carcinoma. http://www.esmo.org/Guidelines/
Genitourinary-Cancers/Renal-Cell-Carcinoma Accessed Jan 2016
20NICE Pathways. Renal cancer overview. Available: http://pathways.nice.org.uk/pathways/
renal-cancer#content=view-node%3Anodes-second-line-treatment-for-advanced-andmetastatic-renal-cancer Accessed Jan 2016
21 N
HS England. Cancer Drugs Fund Decision Summary: January 2015. Available: http://www.
england.nhs.uk/wp-content/uploads/2015/01/ncdf-summ-everolms-post-tki-mrcc.pdf
Accessed Jan 2016
22Wagstaff J. et al. Treatment patterns and clinical outcomes in patients with renal cell
carcinoma in the UK: insights from the RECCORD registry. Ann Oncol, 2016, 27(1):
159–165.
23ABPI. International Comparison of Medicines Usage: Quantitative Analysis. http://www.abpi.
org.uk/our-work/library/industry/Documents/meds_usage.pdf Accessed Jan 2016
24IMS Health, MIDAS- Sales Data Feed
25European Medicines Agency. Inlyta, INN-axitinib. http://www.ema.europa.eu/docs/en_GB/
document_library/EPAR_-_Product_Information/human/002406/WC500132188.pdf
Accessed May 2016
26NHS England. Cancer Drugs Fund Decision Summary: Axitinib in renal cell cancer patients
progressing on therapy with either a tyrosine kinase inhibitor or a cytokine. https://www.
england.nhs.uk/wp-content/uploads/2015/01/ncdf-summ-axitinib.pdf Accessed May 2016
27NHS England. Service Specification: Urological cancers – specialised kidney, bladder,
and prostate cancer services. https://www.engage.england.nhs.uk/consultation/clinicalcommissioning-wave8/user_uploads/urolgcl-cancrs-spec-kidny-blddr-prstte-service-spec.
pdf Accessed April 2016
28Cancer Research UK. Delay Kills. http://www.cancerresearchuk.org/prod_consump/groups/
cr_common/@abt/@gen/documents/generalcontent/cr_085096.pdf Accessed Feb 2016
29Macmillan Cancer Support. Patient Experience of Care. http://www.macmillan.org.uk/
Aboutus/WhatWeDo/Ouresearchandevaluation/Programmesofwork/PatientExperience.
aspx Accessed March 2016
30GP Online. Red flag symptoms: Haematuria. http://www.gponline.com/red-flag-symptomshaematuria/genito-urinary-system/renal-disorders/article/846054 Accessed Jan 2016
31Public Health England. Kidney cancer on the rise. https://www.gov.uk/government/news/
kidney-cancer-on-the-rise Accessed Apr 2016
32 N
ICE. Suspected cancer: recognition and referral. http://www.nice.org.uk/guidance/ng12/
chapter/1-Recommendations-organised-by-site-of-cancer#urological-cancers Accessed Jan
2016.
7
KIDNEY
CANCER:
A SPOTLIGHT
ON THE
CHALLENGES
Date of Prep: May 2016.
Job bag number: ONCUK1600557-01.