Improving survival and Clinical
Trials
Janyne Afseth
Aims
Identify the factors which may link to improved
survival to clinical trials in cancer
Describe some of impact of clinical trials on survival
Discuss some variables that affect participation in
clinical trials
Reflect on the challenges for clinical trials in the
coming decade
Clinical trials – how common are they?
Who knows anyone who has participated on a
clinical trial?
Do you think it was a good idea?
Do you know what the result of the clinical trial
Cancer and Clinical trials in the UK
In England, the National Cancer Research Network (and
equivalents in Scotland, NI and Wales) was formed
approximately a decade ago to increase accrual to cancer clinical trials.
These networks were implemented to improve infrastructure
and access to all patients to clinical trials including those in smaller centres or with less common cancers
It would also allow an increased focus on academic trials
The UK is the most heavily funded EU country for Cancer Research
Success?
More patients in trials
4% in 2001, 18% in 2010. US by comparison has 3%
(NCRN, 2011)
Research outside major cancer centres
All cancer research (including basic) has gone from 12.5% in
major centres in 1995 and increased to 25% by 2004
(Sullivan et al 2010)
Less common cancers
Breast Cancer has approximately 20% of cancer specific
spend (16% incidence) – lung cancer just over 5% (13% incidence) - but this is up from 3% in 2001.
overall spend has doubled in this period
Do patients do better in clinical trials?
Some evidence that patient who participate in centres
where clinical trials are the norm do better
The American Federation of Clinical Oncologic Societies
maintains that
– “treatment in a clinical trial is often a cancer patient’s best option”.
Discussed in UK cancer research network literature
Why might patients do better?
Some treatments might work
Centres where trials are done may have access and
knowledge for newer treatments – for example
Intensity Modulated Radiotherapy (IMRT)
More surveillance (increased follow-up – sooner
diagnosis of progression)
Increased healthcare input – more time with
clinicians, research nurses
Breast Cancer – A Short History of Success
In 1895 a surgeon discovered that the ovaries if taken out tocould decrease breast cancer growth
President Nixon declared a war on Cancer and in the 70’s and
80’s trials with Tamoxifen started (initially developed a birth control)
1980s the UKs Early Breast Trialists Collaborative Group was
formed an pulled together all trials – and results of Tamoxifen preventing the return of breast cancer were accepted –
reduced death by 1/5th
They also found chemotherapy in younger women (<50)
Other success
ATAC – aromatase inhibitors further improved survival
reported early this century – reduced recurrence by
26%
(ATAC Trialists group, 2005)
Taxanes improve reduce recurrence
(Ferguson et al, 2007)
HERA trial – Herceptin in her-2 positive women
decreases recurrence by 50%
(Gianni et al., 2011)
Lung Cancer - successes
How many people lived for at least a year
14% vs.. 16%
5.9 months vs. 6.3 months progression free
(CRUK, 2011)
Some success in extending life by a week or two
BUT
QALY Quality Adjusted Life Year – if only extending by
a short time and expensive – will it be funded?
Have we improved outcomes?
Lung Cancer – survival at 5 years has not changed
since 1971 – has gone from 4% to 8%
Why? – late diagnosis, fast growing, doesn’t respond to
treatments
Breast Cancer 5 year survival – 52% in 1971, now is
82%
Why? Screening programme, Better surgery, improvements
Why aren’t more patients on trials?
Clinician motivation, preference and resources
Breast and colorectal more likely to recruit patients,
oncologist more likely than surgeons and those in cancer centre more likely than district hospitals (Ford et al, 2011)
Patients views
83% of cancer patients would participate in an ‘Randomised
controlled trial’ using a general survey of attitudes (Jenkins et al., 2010)
Informed voluntary consent is required by law
Why aren’t more patients on trials?
Patients often excluded
Patients with poor performance status Patients with significant comorbidities The elderly are under represented
Those in residential care
Patients who don’t want to
travel
Where is cancer research headed
NCRI cancer spend doubled from 2001 to 2010
Improved recruitment to trials
BUT in the last decade targeted therapy and
treatments are emerging
Genetic variations determining targeted treatments,
trials more selective = decreased recruitment
What are the challenges
Now need to assess for molecular targets and can
only test after consent
Less patients eligible for each trial – needs to run
longer
As survival increments smaller need more patients to
prove statistical significance
NHS resources stretched
Treatment resources New technology
Why we need to keep doing research
Evidence based care
Quality of life
Enriching the NHS as dynamic cutting edge
environment
AND MOST OF ALL
To improve the outcomes of the patients who are
affected by cancer
References
ATAC Trialists' Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in
Combination) trial after completion of 5 years' adjuvant treatment for breast cancer, The
Lancet, Volume 365 (9453) 60-62
Cancer Research UK (2011) http://info.cancerresearchuk.org [accessed 21 November 2011]
Ferguson T, Wilcken N., Vagg R., Ghersi D., Nowak A K. (2007) Taxanes for adjuvant treatment of early breast cancer. Cochrane Database of Systematic Reviews Issue 4 John Wiley & Sons, Ltd Chichester, UK
Ford, E., Jenkins, V., Fallowfield, L., Stuart, N., Farewell, D., & Farewell, V. (2011). Clinicians' attitudes towards clinical trials of cancer therapy. British Journal Of Cancer, 104(10), 1535-1543
GIANNI, L., DAFNI, U., GELBER, R. D., AZAMBUJA, E., MUEHLBAUER, S., GOLDHIRSCH, A., UNTCH, M., SMITH, I., BASELGA, J., JACKISCH, C., CAMERON, D., MANO, M., PEDRINI, J. L., VERONESI, A., MENDIOLA, C., PLUZANSKA, A., SEMIGLAZOV, V., VRDOLJAK, E., ECKART, M. J., SHEN, Z., SKIADOPOULOS, G., PROCTER, M., PRITCHARD, K. I., PICCART-GEBHART, M. J. & BELL, R. (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. The Lancet Oncology, 12, 236-244.
References (continued)
Jenkins, V., Farewell, D., Batt, L., Maughan, T., Branston, L., Langridge, C., & Fallowfield, L.
(2010) The attitudes of 1066 patients with cancer towards participation in randomised clinical trials. British Journal Of Cancer, 103(12), 1801-1807.
MITCHELL, C., RICHARDS, S., HARRISON, C. J. & EDEN, T. (2009) Long-term follow-up of the United Kingdom medical research council protocols for childhood acute lymphoblastic leukaemia, 1980-2001. Leukemia, 24, 406-418.
National Cancer Research Network (2011) ncrn.org.uk [accessed 14 November 2011]
National Institute for Health and Clinical Excellence (2011)
http://www.nice.org.uk/newsroom/features/measuringeffectivenessandcosteffectivenesstheq
aly.jsp [accessed 21 November 2011]
SULLIVAN, R., LEWISON, G. & PURUSHOTHAM, A. D. (2011) An analysis of research activity in