On our kidney cancer bloggers page, you will find posts and blogs from kidney cancer patients, carers, family members, kidney cancer specialists, nurses and members of the KCSN about topics that are close to their hearts and of interest to others whose lives are touched by kidney cancer.
We also have the Kidney Cancer Bloggers site, an extension to the KCSN page, which has been setup as a separate site to enable patients, carers, survivors and clinicians to share their thoughts and experiences with others. Please click on the button below to take you to the Kidney Cancer Bloggers site.
However, they did not give anything away as far as the ICER was concerned and the discussions surrounding the patient access scheme (PAS) were commercial in confidence, so I don’t know what was agreed! We get the feeling that the meeting was a formality; they have already made up their minds and we hope that nivolumab will be funded by the new Cancer Drugs Fund (CDF) while further survival data is collected from CheckMate 025 and the Early Access to Medicines Scheme (EAMS).
We’ll keep you posted with more news when we hear it! The Final Appraisal Document (FAD) is expected to be published next month.
The following blog was written by Lisa Steen, a former GP and trainee psychiatrist, who has since died. This patient perspective essay was originally published by the British Medical Journal on 25th August 2016.
Lisa was a very active member of the KCSN and the KCSN Facebook group. She offered friendship and encouragement to other kidney cancer patients and was a great support. We have permission to publish the piece from her husband, Raymond Brown.
I am a GP, formerly a trainee psychiatrist and now 43 years old. In July 2014, I was diagnosed as having kidney cancer with multiple bone metastases. The cancer was extremely rare, associated with a succinate dehydrogenase B (SDHB) mutation. This genetic condition was later also found to be the cause of my carotid body paraganglionoma which had appeared when I was 18 and was finally excised when I was 27.
I had felt unwell in terms of dizziness and visual symptoms since August 2012, and presented to my GP in September 2012, nearly two years before my diagnosis was made in July 2014. So I spent two years wandering in the wilderness of the medically unexplained.
In fact I had been feeling tired for several months even prior to this presentation in August 2012, and had felt like I was lacking concentration. I had been put on a series of antidepressants, each of which caused “side effects” which may have been symptoms of illness all along. Fluoxetine caused headaches, sertraline caused diarrhoea, and dosulepin caused visual disturbance—at least that’s what I thought at the time.
I had considerable difficulty describing my symptoms: primarily visual disturbance; a sense of being behind a wobbly TV camera; also of diplopia—another image slightly below causing blurring, and negative palinopsia, prompting the GP to refer me to the eye clinic urgently, where all examinations were shown to be normal.
There were many other minor symptoms too: fatigue, palpitations, cramps in my hands and feet, subtle cognitive impairments, difficulty finding words, memory problems, difficulty coping at work. I had time off sick even though I previously had an intact sick leave record. I had headaches which were worse on standing, also an altered sensation in a glove and stocking distribution, mild tremor, and gradual weight loss without dieting.
My GP sent me to a psychiatrist mainly because I had been on so many antidepressants, and we didn’t know which to choose next. But also because I had initially interpreted these symptoms as SSRI withdrawal or dosulepin side effects.
The psychiatrist’s immediate instinct was that the illness seemed “organic” not psychiatric, and neither was it SSRI withdrawal or dosulepin side effects.
A neurologist’s advice was sought and her first thoughts were of hypothyroidism or low calcium. The neurologist also requested an ultrasound of the neck as I had concerns that it was something to do with my previous carotid body tumour, and I wondered if it had returned.
The ultrasound and bloods proved normal. The neurologist did not find anything abnormal on examination apart from a Horner’s syndrome (longstanding and related to the previous carotid body surgery). An MRI of my head was subsequently normal.
The psychiatrist made a diagnosis of depression and health anxiety.
I did not entirely believe my psychiatrist however, mainly because the visual symptoms were so florid. I considered myself very psychologically aware and was not convinced about the anxiety/depression diagnosis. Though, unfortunately I had proved a highly suggestible subject during the cognitive behavioural assessment, due to having been trained in CBT myself.
The symptoms did indeed get worse with stressful situations, but this was partly because those situations occurred whilst standing—such as presenting patients on the morning ward round. This had been a factor in stopping work, because there were problems with my word finding and memory. On reaching the patient’s bedside I found myself almost hallucinating in terms of palinopsia, purple haze and blotches, all of which was very distracting whilst trying to contribute to the ward round. It was impossible really to continue working without working life becoming a total humiliation. This did indeed lead to low self worth and anxiety. The low level acute confusional state, as I now see it, meant that I was functioning at a suboptimal level at work, for no clear reason, this then led naturally to anxiety and concern. It was then difficult for me to untangle my own symptoms from psychiatric ones.
Since I was being paid to be off sick, I felt it my duty to follow orders. So therefore to pursue psychological cure—though at the same time I was reading about the physical causes of my symptoms.
I spent the next few months trying to address my apparent mental health problems with a psychologist, and I mainly considered myself to have a psychosomatic illness maybe some sort of conversion disorder. Unusually, I worked backwards, as it were, to exclude a psychiatric illness so as to realise I had a medical illness.
But I gradually became convinced that exertion and not anxiety caused the visual symptoms to worsen, I also thought that the nature of the symptoms “felt” organic because of the pronounced and ongoing visual symptoms.
I then started to look for threads, clues, and a way forward to get treatment. This was thwarted by my earlier diagnosis of health anxiety and having medically unexplained symptoms. One could not be dogmatic in further requests for investigations for fear of looking even more “anxious” or suffering from “health anxiety,” aka a hypochondriac. I wanted to ask the GP for a chest x-ray and abdominal ultrasound, and thought about paraneoplastic syndromes but I always tended to think it was not cancer, in view of the normal inflammatory markers and the length of time it had gone on. But I suspect also it was a pitfall of being forced into the “physician heal thyself” situation.
I saw a vascular surgeon, privately, wondering if the carotid was narrowed by scar tissue from the previous surgery, thinking maybe inadequate blood supply to the brain/retina could be occurring—which is the cause of physiological palinopsia. The carotid was not narrowed, but the vascular surgeon who performed the duplex ultrasound suggested that I might have a genetic disorder and have a phaeochromocytoma, which was something that impacted on his field. I persuaded my GP to order a 24 hour metanephrine test which frustratingly came back negative. At my behest the GP also did blood tests for SLE, and infectious serology screen.
In Spring 2013, I presented to A&E with palpitations, whilst on holiday (the palpitations unhelpfully disappeared on arrival in A&E). The heart rhythm was normal, but the A&E doctor was convinced she heard a third heart sound, and suggested a follow up.
So the next relevant thing seemed to be referral to a cardiologist, in June 2013. I suggested to the cardiologist the possibility of a genetic syndrome related to carotid body tumours. The cardiologist was a kindly man, but after exclusion of any cardiac conditions with an echo and 24 hour tape he began to consider the initial health anxiety diagnosis—or at least it looked like that to me. Once again a kind of consulting room glazing occurred and I was left once more looking like a goldfish. My mouth moving but no sound conveyed to the doctor’s ears. This was by now a familiar feeling to me.
The cardiologist did at least acquiesce to my suggestion that I may have POTS syndrome: postural orthostatic hypotension and suggested referral to a specialist. So I could have some excuse for being off sick.
By now I had gone back to work. There had been a rotation, and I was assigned to a consultant psychiatrist, who made it her mission to rehabilitate me back to work.
By August 2013, I hoped that I had found a thread, something tangible that the specialist could investigate secondary causes of. The POTS specialist did at least do a full examination, though he was not worried about my concerns of a possible pulsatile mass on the left flank, and thought my aorta was just rather left of centre. A tilt table test was organised which was “borderline positive.” In February 2014 further urinary and blood metanephrines were normal. All bloods were repeated and normal. The ESR and CRP remained very low.
At this point I gave up my quest: I was back at work, part time with a benevolent boss, and coping, though tired. I had adapted to my visual disturbance and could now function with it, though I was still embarrassed by my word finding difficulties. I tried to be more organised, and write everything down.
I still knew there was something wrong, but it seemed so fruitless going to see specialists. It was so humiliating, feeling like a goldfish with no voice. Watching doctors’ faces glaze over at the multitude of symptoms. Trying to fit it all in with work and looking after my family.
I decided it would have to wait for clinical events to become more diagnosable. I had tried as hard as I felt reasonably possible. It is also taboo to discuss one’s own health in any depth at work, and I was so exasperated by it all that I felt I would cry if anyone were too sympathetic—which doctors might then interpret as a psychiatric symptom.
In February 2014 I had a follow up with an occupational health doctor. This time the occupational health doctor became concerned, and noticed that I had lost weight and suggested seeing a bowel specialist in relation to a change in bowel habit and to see a neurologist about my numb hands and feet.
I went home and gave myself a full examination. This time I was sure. I found a large mass in my left flank.
I saw my GP, but they couldn’t feel it. I saw my POTS specialist a couple of weeks later and he thought it might be an enlarged spleen. He ordered a routine ultrasound.
One evening in June 2014 the junior radiology technician, working on a waiting list initiative, found a solid/cystic mass 10cm in diameter arising from the left kidney.
I was initially jubilant thinking this would turn out to be a phaeochromocytoma—maybe dopamine secreting. And now I could have an “anxietyectomy.” An urgent CT of the abdomen and pelvis was recommended.
The result was not cause for celebration. The CT showed that the mass was arising from the left kidney and was reported as looking like a renal cell carcinoma. There were also multiple sclerotic lesions in the spine, ribs, and pelvis reported as metastases.
By then I had abandoned my psychiatric training. I had felt unable to study because of “brain fog,” however I had managed to get over the many hurdles to get back my GP status, which involved three exams and six months of retraining.
I had just landed a job as GP Lead for Inclusion service, treating patients with drug and alcohol problems. But the news came just a few days after my interview and offer of the post. My progression through medical services was much more efficient after that and I saw an oncologist and the urologist urgently.
I do not know how long I’ll live. It probably won’t be for many weeks. But right now I am glad to be alive, I am grateful for the expensive drug which is holding back the cancer. I am angry at being left in the medically unexplained wilderness and I did not like the way my colleagues looked at me, when they believed me to have health anxiety.
If anyone of the doctors I saw had gone another mile they would’ve stumbled upon it. I almost told them the answer; I repeated over and over my belief of a genetic syndrome linked to the carotid body, something related to it, but they were unable to hear the answer from a patient. They were reluctant to lay their hands on and examine a fellow medic. I was disappointed in finding a very poor appetite for a diagnostic hunt, which may in part be the result of protocolisation and superspecialism. I disliked being unable to order my own tests, and I regret not pulling more strings. I was too embarrassed about my “psychiatric” condition, too confused by not having the whole answer ready.
My story is a cautionary tale to all of us health professionals when we get ill. Illness is somehow not the done thing. It upsets our “them/us” belief system, which helps us cope with the horror of what we see. “We do not get ill, they are ill.” We are a lot more military than we realise.
We are trained to keep going, as if there was a war on. Our workloads are superhuman, and we seriously do not appreciate it if those around us “slack off,” particularly those taking sick leave with depression or stress. “Heaven knows the rest of us are depressed and stressed, all right for some putting their feet up.”
I felt deeply ashamed of being too unwell to work.
The communication was different, it didn’t go the same way that it would have if I was a non-medic. Doctors do not like being told what to do, and if you try obliquely they don’t notice. They don’t worry much as they assume you’ll come back. But it is hard getting to appointments when one is working, and just how many times can you come back if it gets worse? I was beginning to think that our etiquette for being seriously ill is to drop dead on the job—it is fairly common practice, anecdotally anyway.
Mine is a cautionary tale to those treating health professionals, and those of us who are unwell—doctors do get ill, they don’t always know what is wrong with themselves: give them a class A service because it is actually harder getting treated as a doctor than a lay person.
Matt Bates is 26, and was diagnosed with a rare and aggressive form of kidney cancer in the summer of 2014. Matt has undergone surgery and is currently receiving nivolumab treatment on the Early Access to Medicines Scheme (EAMS). Matt decided to set up his website to share experiences, raise awareness and start writing again after leaving a career in local journalism, and focus on his recovery.
This is the latest entry in his blog; to read more about Matt’s experiences and treatment, please click on the following link: Matt Bates.
My Wonder Drug Nivolumab Rejected for NHS Use
6th July 2016
I try to be quite jovial and jokey about my situation on this blog – and in life – because I don’t really see what I’d gain by acting any other way. And that won’t change. But I want this particular blog to be a serious one, in order to shine the spotlight on a decision made earlier this week that has left me in disbelief.
Not only that, but its consequences could impact on thousands of other kidney cancer patients across the UK, both now and in the future.
Just last week I wrote a blog about how well my new treatment, Nivolumab, is going. If you haven’t read it, I basically wax lyrical about the drug in 1,200 words. It’s a type of immunotherapy and works by essentially giving your immune system the tools it needs to hunt down and kill those horrible cancer cells. In short, it’s brilliant.
It’s certainly turned around my chances of survival. When I was put on Nivolumab I was at a pretty low ebb. My professor basically said I could take a punt on the new drug or choose another that would prolong my life, rather than save it. It was an easy decision.
Fast forward three/four months and my progress has been remarkable. The majority of my tumours have shrunk by half, if not more, including one particularly fast-growing one that shrunk from 4cm to 2cm – an incredible result for someone who was told to hope for tumour stability in the first scan, not shrinkage.
Being able to share that amazing news gave me a great feeling and I’ve been overwhelmed with the messages of support I’ve since received. But one of the best aspects of writing it was knowing that there would be other kidney cancer patients out there who take hope for their own situation from mine. I knew that those people would agree with my belief that drugs like Nivolumab could be the future of cancer treatment. Amazing results, hardly any side effects (for me at least) – it seems obvious.
And that’s what brings me to the reason behind this blog – and the reason for my disbelief over the last couple of days.
The decision comes via the National Institute for Heath and Care Excellence – otherwise known as NICE (I guess it sounded good at the time). The nice people at NICE decided that Nivolumab is too expensive, and that the quality of life it gives the average patient does not justify its high price.
I don’t pretend to know all the ins-and-outs of the decision so please forgive any mistakes, but I believe that, thankfully, this is just a preliminary decision – so there is still time for NICE to come to its senses and make it available. There’s also time for the US pharmaceutical business behind the drug to lower its price and for the two parties to negotiate a better deal for all parties. Plus, in the meantime there are other ways in which Nivolumab could be funded – such as through the new Cancer Drugs Fund – but there are no guarantees and this is a worrying start. It will take a monumental effort to help NICE change its mind.
Funnily enough I was informed of the rejection on Monday – one day before the NHS’s 68thbirthday. So not the best of presents then – like getting a pair of socks from a millionaire! In 1948 Nye Bevan actually launched the service at a hospital in Manchester which, ironically, is exactly where I was when I heard the news. In fact I was just about to have my ninth Nivolumab infusion at The Christie when I was told.
To be honest, I’d assumed Nivolumab had already been approved by NICE. The drug was in the news a few weeks ago for being one of the fastest drugs ever approved, so I figured that would include kidney cancer. But that approval was in fact for Melanoma, a condition that – I’m told – has even fewer treatment prospects than kidney cancer, which isn’t exactly overwhelmed with different options. But it does have a small band of life-extending drugs and that seems to have been the difference between Nivolumab being approved for one and rejected for the other.
Well, my argument would be this: Nivolumab is a very, very new drug. We don’t know what its true capabilities are. We don’t know just how good it can be. But what we do know is that immunotherapy drugs like Nivolumab – drugs that power up the body’s immune system – are the future. And for that reason, NICE needs to be seen to be supporting it. What incentives would drug companies have to research potential cures if they thought that NICE would just end up rejecting it?
I spoke to a kidney cancer charity boss yesterday who has been instrumental in the fight to get Nivolumab noticed. She told me about a Phase Two trial for Nivolumab in kidney cancer patients from five years ago. Of the patients in that trial, 33 per cent are still alive today. One in three. Apply that probability to my cancer and you get the best odds I’ve ever had since my diagnosis in October 2014. I certainly hope to still be here in five years.
As I said earlier, there is still hope for patients. But it looks like at least one side will have to compromise. Either NICE will have to change its mind on the current pricing or the drug company involved will have to offer a discount. One of the stumbling blocks is actually that another company did offer NICE a discount on a rival drug, and has therefore made Nivolumab look extra expensive. Hopefully a similar discount deal can be brokered here – there’s too much at stake for any other outcome.
I’ve never met anyone at NICE and I don’t know how it operates or how decisions are made. But I imagine that the people who make them don’t take the job of rejecting potentially life-saving drugs lightly. I bet it’s a bloody hard thing to do – to rubber-stamp a decision knowing you are taking options away from health professionals. At the end of the day, everyone wants to cure cancer. As the Cancer Research adverts tell us: “We will beat cancer.” Of course, what they don’t add to that is “But only if it fits into a cost-effective model first.”
In all seriousness, of course money needs to play a part in the process of selecting which cancer drugs are used and which are discarded. As the now famous article on the launch of the NHS said: “You are all paying for it, mainly as taxpayers, and it will relieve your money worries in times of illness… But it is not a charity.”
I get that. But it is hard for me to comprehend Nivolumab’s rejection when it has completely transformed my odds of survival. I’m very lucky in the fact that I, and apparently around 250 others in the UK, should continue to receive the drug. But other people – who weren’t in the right place at the right time when the chance to take Nivolumab came around – won’t get that chance. Is that right? Is that a system that is working?
Is it fair that the decision to hand out potentially life-saving drugs to cancer patients is basically a lottery? Simply a mix of timing, circumstance, luck, geography – are we happy with that?
People at NICE have to live with the decisions they make. People with cancer may not be that lucky.
P.S. If there are any other kidney cancer patients out there who are taking Nivolumab, I’m told the Kidney Cancer Support Network wants to hear from you as they gather more evidence to try and get this decision overturned. Click here for more.
P.P.S. I was interviewed by Sky News Radio (who supply news for lots of commercial radio stations) about the news – and I’m told there’s a chance it might get aired on various stations. It coincides with the Chilcot Inquiry report on Wednesday so will be at the back of the queue but if you listen to the commercial stations – particularly the locals one for Warwickshire I imagine – you might hear me. Hopefully other press will pick up the refusal soon so the decision can get some exposure.
A small group of us from KCSN went to the NICE nivolumab single technology appraisal (STA) meeting on Wednesday 8th June. KCSN recommended two patient experts to contribute to the meeting, while the rest of us were public attendees and unable to voice our opinions (unfortunately!).
- The bulk of the evidence for nivolumab came from the CheckMate-025 trial of nivolumab versus everolimus in the second-line, and a network meta-analysis that compared nivolumab with axitinib. There were differences in the trial populations, and there were more poor performing patients in the meta-analysis than in CheckMate-025. The committee questioned whether the trial populations were comparable, since the CheckMate-025 patients had an overall better prognosis than the meta-analysis patients, thereby potentially underestimating the effectiveness of axitinib. Which trial population is more generalisable to NHS patients? The clinical experts both agreed that in clinical practice only a small proportion of poor performing patients would qualify for second/third- line treatment, and therefore the CheckMate-025 population was closer to reality.
- The network meta-analysis was carried out because there are no randomised clinical trials to compare nivolumab and axitinib or axitinib and everolimus. The clinical experts stated that in clinical practice axitinib and everolimus were similar, although clinical trials show that patients do better on second line TKIs.
- In the CheckMate-025 trial, nivolumab reduced the risk of death compared to everolimus; however, the survival curves for nivolumab and everolimus appeared to converge at around 28 months, meaning there was no difference between everolimus and nivolumab. The clinical experts disagreed with this, and made the committee aware of new phaseI/II data presented at ASCO last week showing that the survival curves for nivolumab plateaued (levelled off) and around 1/3 of patients survived for at least 5 years. These data had been presented to the NICE committee, but not included in the health economic modelling.
- The patient experts were asked about an intravenous injection versus daily tablets, and the impact on quality of life. Both agreed that because nivolumab was well tolerated and appeared to provide benefit to patients, the impact of an intravenous injection on quality of life was acceptable.
- The NICE committee questioned some of the methodology used by the company for the cost effectiveness analyses, and whether the assumptions used in the analyses reflected NHS patients, and whether the data represented second or third line use of nivolumab. The clinical experts suggested that if they had the choice between second and third line, they would give nivolumab sooner to enable a greater duration of action.
- The cost effectiveness calculations were done using the list price of nivolumab and did not include any discounts/patient access schemes negotiated with the company (this was conducted in private after the public meeting). Because of the NICE committee’s disagreement with the cost effectiveness methodology used by the company, they calculated a different incremental cost effectiveness ratio (ICER). The company’s ICER was £42,417 and the committee’s ICER was £74,132. Both estimates are higher than the NICE threshold of £30,000.
- It is the first checkpoint inhibitor immunotherapy to gain marketing authorisation for advanced RCC – it is an innovative, new drug and we do not yet know the long-term benefits of this class of drug in RCC patients.
- It is better tolerated than the drugs we currently have for RCC – quality of life is improved, and for some patients this has been life-changing and people have been able to live normal lives again.
- There is some evidence, although small, that the drug can prolong the lives of RCC patients for at least 5 years – the company need time to collect more evidence to prove this effect.