Provincial Reimbursement of Afinitor and Torisel

Our efforts to raise the patient voice have been successful in so many provinces, but unfortunately not in all. For example:

• Afinitor is still not funded in the provinces of Manitoba or PEI. To date, patients in Manitoba have had case-by-case access, but our goal is to see the province include second line treatment on their official formularly. Patients in PEI have no access whatsoever.
• Torisel, a drug that was Health Canada approved MANY years ago, is still not funded in every province, most notably not in Quebec where the provincial government has denied access three times and has agreed to re-review.

For more information on what’s available in your province, check our drug access document on our website here.

Upcoming: Reimbursement of Votrient

Now that pCODR (pan-Canadian Oncology Drug Review) has made its official recommendation to the provinces, it’s up to each one (except BC and QC who have already announced first-line funding without restrictions) to decide how and when they will reimburse Votrient. Our expectation is that the current Patient Assistance Program will close (to new patients only) in several months so there is an urgency for provincial drug programs to step up to the plate and follow the pCODR recommendation. We’ll be watching very closely.

New Treatments on the Horizon

2012 should be the year that we see several new treatments receive FDA approval in the U.S. We’ll be gathering information about those treatments and how patients might be able to access them in Canada. As always, we’ll be watching for Health Canada approval to follow the FDA.

Canadian Healthcare’s Bigger Picture in 2012 and Beyond

The 2014 Health Accord has been in the news a great deal since our Federal Government’s financial announcement just before the holidays. From a national perspective, we are concerned about the lack of commitment to national pharmacare (a national catastrophic drug program), lack of national standards of care, and lack of accountability for how the funds will be spent by each province.

Kidney Cancer Canada is publicly supporting the Canadian Medical Association and Canadian Nurses Association, along with many other patient organizations in calling for patient-centred principles for healthcare transformation. For more information on this joint statement, please see our website:

http://www.kidneycancercanada.ca/main.php?p=890&lan=1

http://www.cma.ca/health-care-transformation.

Stay tuned for how we will move forward in 2012. If there are issues in your province that we may not be aware of, please do let us know at:

info@kidneycancercanada.ca

That’s where is trouble started. Now, some of you will remember that we celebrated earlier this year (July) when the New Brunswick government announced funding of Afinitor in the second-line for those patients on the public drug program. This patient didn’t need the government’s plan, because he has been paying for private drug  insurance ever since he retired (normally a good move in anyone’s book!)

However, this time the wheels of the insurance company were turning slowly, if indeed they were turning at all. Although the NB formulary had added Afinitor in July, the insurance company had not yet decided whether to add the drug to its list of drugs covered. And so they kept him waiting… and waiting… and waiting while they reviewed the case. Weeks turned into months while he waited for bureaucrats within the insurance company to decide whether he could have the drug or not.

On the patient’s behalf, KCC wrote to the insurance company and we were told that a decision (positive or negative) would be made by the end of the month. In the meantime, we had put the patient in touch with our contact in the media. A front-page story appeared today in The Daily Gleaner in Fredericton:

http://telegraphjournal.canadaeast.com/front/article/1459946

As an addendum to the news story, it’s worth noting that a 5 pm yesterday, the patient was called with the news that Afinitor had been approved for him, at least for 4 months.

Unfortunately the stress and anxiety caused by the insurance company cannot be undone. Nor can the tumour progression that happens when advanced kidney cancer patients go without needed treatment. Surely someone in these organizations can show a little compassion and expedite a request when it is for a life-threatening condition.

Surely that’s why we buy private insurance in the first place — to cover us when we need it most.

“Good Job, with Benefits”

First this week, someone close to me was offered a new position in a good company that has over 100 employees. On closer inspection, the medical coverage (including dental, vision, and pharmaceutical coverage) would cap at $2,000 per year. As many of you reading this know, $2,000 would not even cover 2 weeks’ worth of cancer drugs for kidney cancer. Perhaps having this kind of coverage is worse than not having any at all. (At least if you have none, you know you have none and can make a conscious decision to find private coverage somehow on your own.)

At Kidney Cancer Canada, we often get calls from patients or families who thought they had private insurance that would cover them. Many of us are capable of covering the odd $50 prescription for antibiotics, so we’re not prepared for drug costs of over $6,000 per month.

Your employer’s group plan depends upon where in Canada you live, the insurance carrier, and most importantly how much coverage your employer has purchased. We encourage anyone denied coverage to work through their employer’s HR department first because ultimately the employer is the client of the insurance company. As employees though, we might all want to keep an eye on our benefits programs and changes being made by our employers to reduce the growing cost of these plans. It’s worth finding out what you would be covered for. If you leave your job (willingly or not) or retire, can you continue coverage even at cost to you?

Globe Article: Catastrophic Injury Without Insurance

The second prompt this week was an excellent article in today’s Globe & Mail that focuses on catastrophic injury and how our healthcare system covers the acute care in the hospital setting, but leaves a patient without insurance completely in the lurch once they are discharged:

http://www.theglobeandmail.com/life/health/medicares-no-match-for-catastrophic-injury/article2234387/

Disclaimer here: I don’t work for the insurance industry and no family member does either, but my proverbial bacon has been saved by some young whipper snapper (thank you Ian) who once told me to purchase private disability insurance even though I had a decent job at the time AND by an employer plan that (at least currently) pays 100% of my prescription drug costs.

If I was young, or if I had the chance to speak to young Canadians, I would urge them to purchase private insurance now while they are young and healthy. Don’t expect your Canadian public healthcare system to pick up the costs of a catastrophic injury or illness. And don’t expect your employer’s plan to cover everything like in the “good old days” of lifetime employment. Unfortunately, the trends are just not heading in that direction. For reference, see the Cancer Advocacy Coalition’s excellent article on trends in private insurance in their 2009 Report Card.

For some relatively neutral information about private insurance, you can check out the Canadian Life and Health Insurance Association’s website:

A Guide to Supplementary Insurance
A Guide to Disability Insurance

We’ll continue fighting for access for all Canadian patients to all proven therapies for kidney cancer, but until the Canada Health Act is reworked to include medications outside of a hospital setting, we might all want to buy or hang on to whatever insurance we can afford.  As we get closer to renewing the Health Accord in 2014, it will be important for all Canadians to make cancer drug access a priority for our Federal Government.

Comments? Sad but true?

Earlier this summer we asked Canadian patients and families to answer a survey about treatment options. Over 120 people responded with information about how patients consider treatment options, risks, benefits, and quality of life. From all of that information (thank you all!), we put together a detailed Patient Evidence Submission for the new pCODR (pan-Canadian Oncology Drug Review) process for their evaluation of pazopanib (Votrient). We included statistical summaries of your responses and some anonymous quotations from patients and caregivers from across Canada.

The pCODR process has now announced an interim recommendation, and as your patient voice in the process, we have the opportunity to submit comments on or before November 18, 2011. In short, the recommendation from pCODR is to recommend the reimbursement of Votrient for those patients who are unable to tolerate Sutent.  We were not expecting the condition (of the patient being unable to tolerate Sutent) — and indeed this is not the case in the provinces of British Columbia and Quebec where Votrient is fully reimbursed as one of the choices in the first-line therapy setting.

If you’re interested in this kind of thing, please take a look. If you have have comments, please feel free to post them here or email us at info@kidneycancercanada.ca

http://www.pcodr.ca/portal/server.pt/community/find_a_review/547/pcodr_-_find_a_review_detail

The good news is that the submission from Kidney Cancer Canada was referenced several times in the expert review. We are really proud of the data that you helped us pull together, and the genuine comments that ensured reviewers heard from patients and caregivers directly.

At the end of the day, we just want patients to have access to proven treatments — those that are Health Canada approved and make sense for patients with kidney cancer and the oncologists overseeing their care. Surely the fewer roadblocks and hurdles we can throw in their way, the better.

Day 2, Discussions were on several key topics. Full presentations may be accessed at the following link: http://kca.omnibooksonline.com/chicago2011/index.html

1) Molecular Insights in RCC

FOXo Transcription Factors in mTORC1, Dr.Boyi Gan:

• FoxOs are a kind of transcription factor (signaling factor, which transmits signals to proteins of cell to do certain tasks)
• Mammals possess FoxO1, FoxO3, FoxO4, FoxO6
• 1/3/6 are regulated by P13/AKT signaling
• Broad somatic deletion of all 3 Fox0s, is associated with cancer prone conditions such as hemangiomas and lymphomas
• Inactivation of FoxO & TSC1 dramatically drives renal tumour progression
• FoxOs are extininguished in many renal cell tumour types
• Myc signaling is the key downstream effector of FoxO, in the regulation of renal tumours

Future research in targeted therapies should include a combination of mTOR & FoxO targets in RCC

Gene Polymorphisms in predicting efficacy and safety with Sunitinb, Dr. Astrid van der Veldt

• Approximately 35% of metastatic RCC patients do not benefit from Sutent therapy
• Sutent therapy is associated with a wide range of toxicities
• Pre-treatment markers to help identify patients which will benefit from Sutent therapy are needed.
• Study included 290 RCC patients from 6 Dutch centers
• 37 polymorphisms in 15 candidate genes were analyzed.

Concluded that Pharmakokinetic polymorphisms are independent predictive factors of PFS (Progression Free survival) in Sutent treated patients. Polymorphisms in genes encoding metabolic enzymes, efflux transporters and drug targets are associated with Sutent toxicities.

Clinical Applications of genomic Classification in RCC, Dr. Brian Rini, Cleveland Clinic, Ohio
Genetic mutations in mRCC continue to evolve:

• VHL (Von Hippel Lindau) inactivation does not seem to be a predictive factor, at present
• PBRM1 & related mutations, recently discovered, clinical significance is yet to be made clear
• SNPs (Singe nucleotide polymorphisms) have promise in RCC, further work is required
• RNA gene expression in RCC is in initial stages of discovery

Clinical relevance is being studied

2) Surgery in treatment naïve RCC
Role of Cytoreductive Nephrectomy, Dr.Gerald Mickisch

• Cytoreductive nephrectomy was well established in the era of immunotherapy with Interferon in RCC.
• The role of Cytoreductive nephrectomy in the era of targeted therapy is yet to be determined. Clinical trials are underway and their outcome is eagerly awaited.
• Meanwhile cytoreductive nephrectomy continues to be standard of care in RCC.

Systemic Therapy is the best initial treatment, Dr. Erich Jonasch, MD Anderson cancer Center
A significant number of patients are not candidates for upfront nephrectomy.
In these patients initial therapy and careful monitoring, enables better planning in the time of nephrectomy
This type of planning is especially helpful, if the initial tumour is unresectable, and then targeted therapy makes the tumour smaller and resectable.

3) Systemic Therapy, Dr. Bernard Escudier
Many combinations have been tested, many proven to have a lot of toxicities and very limited benefit

• TKIs (Sutent & Sorafenib) & Avastin combination is too toxic
• mTOR inhibitors (Afinitor & Torisel) & TKIs (Sutent & Sorafenib) combination has very limited benefit
• Tivozaninb & Temsirolimus combination has shown some benefit in 10 patients, in a study, at their clinic
• mTOR inhibitors (Torisel & Avastin) combination, shows some hope. Side effects are manageable. Efficacy is not outstanding
• TORAVA study, showed best efficacy in the Avastin + IFN arm (PFS 16.8 months) versus the Sutent only arm (PFS 8.2 months)
• Avastin + Afinitor combination showed PFS of 7.1 months and OS (Overall Survival) of 14.5 months. Data are good, but we are not sure, if they are better than Afinitor alone.
• Large Phase 3 study, INTORACT, 2 arms (Avastin + Torisel versus Avastin + IFN) should report soon.
• RECORD 2 (Avastin + IFN versus Afinitor +Avastin), Phase 2 study should report soon.
• Phase 2, first line study of Sorafenib +/- AMG 386 ongoing
• Phase 2, first line study of Sutent +/- AMG 386 ongoing

Other molecules being studied:

• AGS-003: RNA loaded dendritic cell based vaccine
• IMA 901: based on 10 naturally presented tumour associated peptides
• Tremilimumab+ Sutent

Intermittent VEGF inhibition, Dr. Viktor Grunwald
Two studies enrolling 12 & 36 patients each were discussed. Patient were from European centers. In all patients were on different targeted therapies, and all had their treatment discontinued and then that patients were observed.
The studies showed:

• Complete clearance of tumour is rare in RCC
• Tumour relapse was seen in 67% of patients, after a median of 7 months, but long term DFS (Disease free survival) may occur
• Clinical predictors of DFS could not be determined
• Sensitivity to targeted treatments is retained at the time of relapse
• Stopping of treatment remains a valuable option in selected RCC patients

Current Strategies to Overcome resistance, Dr. Thomas Hutson
Current Strategies include:

• Increase dose of same targeted agent
• Switch to another VEGF pathway blocker
• Sutent after avastin
• Axitinib after front line therapy
• Axitinib after sorafenib
• Drug holiday and Re-challenge: best demonstrated with Sutent
• Switch to mTOR inhibitor, either alone or in combination

Newer therapies:

• Fibroblast Growth Factor receptor is a target in RCC
• TKI258 (Dovitinib), has shown promising activity in Phase 2
• Phase 3 trial is ongoing: Dovitinib versus Sorafenib, after progression on VEGF targeted therapy
• BNC 105 P produces necrosis in cell that express high level of mTOR
• Ongoing study of BNC105 P in combination with Afinitor versus Afinitor alone

Problem of primary resistance to targeted therapies, which occurs in 20% of RCC patients remains a problem and is not clearly understood.

4) Side Effects
Nursing Issues in Toxicity management: Laura Wood, RN
Key issues nurses deal with on a daily basis are;

• Drug Interactions
• Chronic Kidney disease
• Nutritional support
• Drug interactions:

Common websites, which can be used to gain information on Drug Interactions, are:
• Lexicomp: www.kexi.com
• Up to date: www.uptodate.com
• Drug Information on Line: www.drugs.com
• Indiana University division of Clinical Pharmacy
It is very important to tell patients to keep a record of all medication they have taken, with start and stop dates. Insist on showing the list to the nurse at each visit.
Chronic Kidney Disease (CKD): Assessment is done by the Glomerular Filtration rate, Cockcroft Gault formula & estimated Glomerular Filtration rate.

If any sign of CKD, remedial measure should be taken immediately
Gastrointestinal Toxicity Management: Of note are:
• Diarrhea
• Nausea & Vomiting
• Mucositis
• Taste Changes
• Anorexia
Early management of diarrhea with loperamide, dietary management & lomotil is highly recommended.

The IKCS Conference was attended by top RCC experts from North America & Europe. Attendees included distinguished RCC treating Medical Oncologists, Surgeons & Nurses. Industry representation from Pfizer, Novartis, GSK & Bayer

This blog post includes a summary of sessions on Day One. Full presentations may be accessed at the following link: http://kca.omnibooksonline.com/chicago2011/index.html

1) Small Renal Masses

Epidemiology:
Dr. David Miller discussed the epidemiology and trends among patients in USA. Kidney Cancer rates have been steadily rising from 8 per 100,000 in 1975 to 18 per 100,000 in 2006. Mean age at diagnosis continues to be around 60.
60% are diagnosed with localized tumours. Most patients are without symptoms, but have significant other diseases (hypertension, dialysis, anemia, etc). Mortality is still a challenge with early tumours.
Why should we move away from Open Radical Nephrectomy?
• Preserve non malignant kidney tissue
• Easier convalescence
• Shorter hospital stay
• Reduce pain at the site of surgery
Laparoscopic surgery has equivalent data for cancer control and has a much easier convalescence. However data show patient are more likely to die, immediately after surgery due to complications.

Renal Mass Ablation
Dr. Thomas Atwell, Mayo Clinic, discussed Radio Frequency ablation (RFA) & Cryoablation of tumours. RFA causes tumour death by delivering electrical current, which in turn produces heat, in the tumour. In contrast , Cryoablation, causes tumour death by freezing.

• RFA is easy to use & is fast & safe. The disadvantage is that it cannot be used for large tumours & it is difficult to monitor its effects.
• Complications include nerve & ureter injury, bleeding & abscess formation
• Cryoablation can be used for large tumours & central tumours. Needs less monitoring. Disadvantages are bleeding, cumbersome to use & takes longer.

In conclusion, both techniques are useful, depends on size & location of tumour.

Active Surveillance of Localized RCC
Dr. Robert Uzzo discussed active surveillance versus treatment for small, renal masses at Fox Chase Cancer center.
• 86% of Small renal masses are 4 cm)
• No patient under active surveillance metastasized
• Average time from detection to metastasis=40 months
The data show that although kidney cancer is a deadly disease active surveillance is an option and calculated risk for some patients.

Nephron Sparing surgery
Dr. Paul Russo, from Memorial Sloan Kettering, suggested that data show routine Radical Nephrectomy (RN) for small renal tumours is unjustified. Urologists need to be made aware that CKD (Chronic Kidney Disease) can be created or pre-existing CKD made worse with Radical Nephrectomy. Still RN accounts for 80% of surgeries for SRM (small renal masses< 4 cm in size).
AUA (American Urology Association) guidelines, strongly support PN (partial nephrectomy), when feasible.

2) Pediatric renal Tumours
Renal tumours account for 6.3 % of cancer diagnoses in children <15 years of age. Wilms’ tumour (nephroblastoma) is the most common, accounting for 91% of all renal tumours during childhood. Other tumours include clear cell RCC, Sarcoid tumour & angiomyplipoma.
Surgery is the best option for Wilms’ tumour, followed by chemotherapy with doxorubicin, etoposide, vincristine & cyclophosphamide in some cases.

3) Localized & Locally advanced Clear cell RCC

Imaging Innovations: Dr. Ivan Pedrosa
Newer Imaging techniques include:
• Contrast enhanced ultrasound
• Dual source CT scan
• MRI
o Arterial spin labeling
o Dual weighted imaging
• PET
All have a very important role in the diagnosis of kidney cancer and in active surveillance of small renal masses

Neo-Adjuvant Therapy: Dr. Christina Suarez Rodriguez
Discussion around a patient given neo-adjuvant therapy with Sutent. Although not a standard therapy, it should be considered in selected cases. Several trials are underway and the outcome is eagerly awaited.

Role of Lymphadenectomy: Dr. Michael Blute
Retroperitoneal lymphadenectomy (RPN) does produce improvement in survival; however there is increase in morbidity (complications & death from surgery)
RPN is currently recommended for:
• High Risk primary disease
• Cytoreductive nephrectomies
• Isolated Retroperitoneal recurrence
RPN is not recommended for Low Risk primary disease

Prognostic factors: Dr. Vincenzo Ficara
Prognostic factors are of 3 types:
• Clinical & Laboratory findings
• Pathology
• Molecular & Genetic
Newer Integrated Prognostic Factor systems take into account:
• TNM (Tumor/Node/Metastasis) staging
• Histologic subtype
• Nuclear Grading
• Coagulative necrosis
• Microvascular Invasion
• Sarcomatoide differentiation
Integrated Prognostic Factor Systems significantly improve prognostic accuracy.
Inclusion of cytogenetic & molecular markers is encouraging and awaits validation.

4) Distinguished lecture
Genetic Basis of Kidney Cancer: Dr. Marston Linehan, National Cancer Institute
There are several forms of inherited Renal Cell carcinoma
1. Von Hippel Lindau
2. Hereditary Papillary Carcinoma
3. Burt Hoge Dube disease
4. Hereditary Leiomymatosis
5. Succinate Dehydrogenase
All have distinct genetic markers. Targeted therapies such as Sutent and Avastin are an option for these forms of RCC

Survivorship research is of particular interest to Kidney Cancer Canada. You might be interested in this paragraph (emphasis added):

Over half (55%) of the average annual investment in survivorship research was focused on specific cancers. For several types of cancer, the distribution of investment in research targeting a given cancer site was similar to or higher than the prevalence (patients still alive after a diagnosis of cancer) for that cancer site. For colorectal, prostate, and bladder cancers, however, the proportion of research investment fell well below the relative prevalence, and there was no investment in survivorship research focused on melanoma or kidney and pancreatic cancers.

Read the release:
http://www.newswire.ca/en/releases/archive/September2011/20/c4831.html

In recent years, the medical community has learned a great deal about what it means to live with kidney cancer, the long-term effects of kidney surgery, and the life-time risks for kidney cancer patients. Unfortunately, not many patients have been given information or a meaningful survivorship care plan.

With over 22,000 people in Canada living with kidney cancer that was diagnosed in the past 10 years, there is increased need to study long-term survivorship. We’re not sure what that investment should look like, but we’re pretty confident that $0 isn’t enough.

Comments?

• Northwest Territories
• Prince Edward Island
• Manitoba
• Ontario
• Newfoundland and Labrador
• Saskatchewan.

(Voters in Yukon are expected to be voting soon as well.)

So, what does this have to do with KCC? As you know, we’re all about healthcare, and there is no better time to talk about healthcare than in a provincial or territorial election! While there are many issues, healthcare spending represents a significant chunk of provincial funds. Are you happy with the decisions your p/t government is making on your behalf? Is the healthcare system we have now the one you want for yourself, your children, and your grandchildren? Either way, now is the time to make your opinions heard.

• Ask your local candidates about their stand on cancer care in Ontario/your province. Are they aware of the issues with coverage for oral cancer treatments for those who don’t have private insurance?
• Ask how they could help you if you needed a treatment for your kidney cancer that was not covered where you live?
• Ask how much they think is too much for you to pay out of pocket for cancer drugs?

Together we have a job to do to make sure that every elected candidate knows that healthcare is a major priority, and that specifically, CANCER care is a major priority. Let’s all try to get people elected who care about cancer patients and are willing to “rock the boat” if necessary to help us get the treatments we need. Remember that whomever you elect this fall will not face this concern themselves. THEY will be covered by the p/t government health insurance program (and yes, that’s drug insurance that your tax dollars will pay for).

I’m voting on October 6th in Ontario. I just don’t know who for yet.

Imagine a day when a simple urine test at your annual physical could detect early signs of kidney cancer. The two studies reported below indicate some potential. Of course, we would still need to know what the appropriate treatment might be for microscopic kidney cancer, but bring on that day!

TWO METABOLON STUDIES PROVIDE INSIGHT INTO KIDNEY CANCER FOR UNIVERSITY OF CALIFORNIA DAVIS

RESEARCH TRIANGLE PARK, N.C. (August 11, 2011) — Metabolon, Inc., the leader in metabolomics, biomarker discovery and biochemical analysis, announces the publication of studies in two peer-reviewed journals that support the use of metabolomics in the diagnosis and treatment of kidney cancer. The studies were conducted by Robert Weiss, M.D. of the Cancer Center at the University of California Davis and colleagues at the University’s Departments of Public Health Sciences and Internal Medicine in collaboration with Metabolon scientists.

The first study, “Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer,” used metabolomics techniques to identify metabolites in the urine of patients with kidney cancer (renal cell carcinoma, RCC) that appear at different levels compared with patients without kidney cancer. The levels of quinolinate, 4-hydroxybenzoate and gentisate, metabolites involved in common biochemical pathways of specific amino acid and energy metabolism, were significantly different in urine from RCC patients. This result is consistent with protein breakdown and utilization as well as the Warburg effect in kidney cancer tumors. Further, the investigators showed that addition of quinolinate, or α-ketoglutarate, which increased significantly in kidney cancer, stimulated growth in RCC cell lines more than addition of gentisate, which decreased.

The article has been published online in OMICS, A Journal of Integrative Biology and may be accessed by this link: http://www.liebertonline.com/doi/abs/10.1089/omi.2010.0094

The second study, “Urinary Acyl-carnitines Are Altered in Human Kidney Cancer,” compared urine samples from patients with and without kidney cancer, using metabolomics. This study found increases in urinary acyl-carnitines in patients with kidney cancer, with the highest levels associated with high cancer grades. Analysis of a Caki1 mouse xenograft model of human kidney cancer suggest the acyl-carnitines are from tumor tissue and may reflect alterations in metabolism or in cell component synthesis. Since higher chain length acyl-carnitines have an inhibitory effect on NF-kB activation, these metabolites may also reflect changes in immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites that may lead to new therapeutic approaches for kidney cancer and may prove useful in future cancer biomarker studies.

The article has been published online in The International Journal of Cancer and may be accessed by this link: http://onlinelibrary.wiley.com/doi/10.1002/ijc.26274/abstract