We worked together at Boston Children’s Hospital in the early 1990’s, before the Internet, and just as a new computer interface called “Windows” arrived. Cricket was a nurse and she took care of the kids on the cancer ward. Her effortless grace with such an enormous task made my job in IT seem easy. I once asked her how she managed to do this every day and she replied, “You have to understand, I have been here a long time. When I started, there was no hope for these kids and now there is some.”
Certainly there has been advancement in cancer since Cricket started nursing in the 1970's. For the Acute Lymphoblastic Leukemia (ALL) kids that she took care of, the five-year survival has improved to over 90% today for children in most developed countries. For other cancers in both children and adults, there has been improvement though not as dramatic and access to new treatments is often the best hope. Unless enrolled in a clinical trial or special program offered by the drug manufacturer, these new treatments are often costly and not covered by insurance.
A new immunotherapy drug called Pembrolizumab, also known as Keytruda, has had impressive results treating advanced Melanoma. Keytruda is also known as "the Jimmy Carter Miracle Drug", as it was part of the former US president's successful treatment of metastatic melanoma even after it had progressed to his brain. Keytruda works when a certain protein (PD-L1) is present on tumor cells. This protein disguises the tumor cells so the body's immune system doesn't recognize the threat of the cancer, and therefore does not attack. Keyruda blocks the protein's disguise, and therefore helps the body's natural immune system to attack the tumor cells.
In 2015, Keytruda took off after The Lancet published results from KEYNOTE-002, a randomized, controlled, phase-2 trial for advanced melanoma, where Keytruda had double the Progression Free Survival at 6 months than chemotherapy, with less than half the adverse effects.
KEYNOTE-002 Advanced Melanoma Trial |
Keytruda |
Chemotherapy |
Progression-free survival @ 6 months |
34% |
16% |
Adverse effects |
11% |
26% |
The following year, the U.S. Food and Drug Administration (FDA) approved Keytruda to treat metastatic non-small cell lung cancer when the PD-L1 protein is present on at least half of tumor cells, based on the results from the KEYNOTE-024 Trial where Keytruda was compared with normal chemotherapy. Then in 2017, the FDA approved Keytruda for any type of cancer, as long as the PD-L1 protein is present.
KEYNOTE-024 Non-Small Cell Lung Cancer Trial |
Keytruda |
Chemotherapy |
Progression-free survival median |
10.3 months |
6.0 months |
Still alive at 6 months |
80.2% |
72.4% |
Adverse effects |
73.4 |
90.0 |
While still a significant improvement, the marginal benefit over chemotherapy has been less for lung cancer than advanced melanoma. As a result, Keytruda is offered as part of New Zealand's Universal Pharmac coverage to patients with advanced melanoma who exhibit the targeted PD-L1 protein, but not funded for the 500 lung cancer patients who have this protein. And, even though Keytruda is administered in public hospitals for melanoma, lung and other cancer patients must have their Keytruda treatments every 3 weeks in a private facility at the cost of about $3000 ($2100 US).
At the risk of minimizing the struggle of these families, the patients who want treatments not publicly funded are a relatively small portion of the entire picture. Last year, New Zealand's Pharmac public health pharmacy provided free cancer medicines to approximately 80,000 patients. This is a 50% rise from 53,000 in 2011. During this same period, Pharmac reports that spending on cancer drugs has doubled and more than a quarter of the spending was on two medicines - trastuzumab (Herceptin) and pembrolizumab (Keytruda). Conversely, without universal coverage, ALL cancer patient in the US face the burden of the cost of treatments, so much that oncology communities have coined a new term, "financial toxicity" for the care they provide.
COST
How much does the miracle drug Keytruda cost?
If you've been reading this blog, you might have noticed a common theme that cost of treatment depends on geography and insurance.
Here is a brief cost comparison based on geography
US
|
New
Zealand
|
UK
|
|
50mg
Keytruda
(costs converted to US$)
|
$2,350
|
$1,867
|
$1,871
|
Besides navigating through options for federal financial assistance, US patients and New Zealand patients seeking treatments not publicly funded have these options:
- Health insurance - About 80% of US patients and 30% of New Zealanders have insurance, however, policies in both countries can have caps and exclusions when it comes to expensive cancer treatments. In the US, New England-based Harvard Pilgrim covers the cost of Keytruda treatments after the annual deductible has been met, assuming the patient meets the clinical guidelines. Medicare plans also state Keytruda is a covered benefit (80% of cost), resulting in patient co-pays approximately $770 per treatment after their deductible has been met. Additional policies to supplement Medicare are common and if the patient has one of these, it might cover the co-pays.
- New Zealand's largest insurer, Southern Cross, has addressed the issue of covering expensive treatments not yet funded by the national Pharmac by offering "Cancer Assist", an optional extra coverage which pays a lump sum between $20-300K to policyholders diagnosed with a 'qualifying' cancer, which is similar to programs available through US insurers.
- Crowd funding - some patients have raised money for treatments through finding websites
- Patient Programs offered through bio/pharma manufacturers - Many biotechnology and pharmaceutical companies have co-pay schemes based on the patient's ability to pay. Merck has a program for eligible Keytruda patients that caps their drug expense at $60K.
- Clinical Trials - with the help of his physician and social worker in the physician's office, a US friend in South Carolina was able to enroll in a clinical trial, therefore paying $35 for a state-of-the-art treatment that would normally cost $20,000. This experience is similar to Dave deBronkart, also known as "e-Patient Dave", who was diagnosed in January 2007 with Stage IV kidney cancer. At the time of his diagnosis, he was told his median survival time was 6 months. With the help of his physician, he found a website of others who had been treated for the same illness and was directed to a specialist and clinical trial at Boston's Beth Israel Deaconess Medical Center. Today, more than 10 years later, Dave is a worldwide advocate for "participatory medicine", encouraging the democratization of healthcare, where patient manage their health in partnership with their physicians.
OPPORTUNITY FOR LOWER TREATMENT COSTS
The cost of treatment also depends on how pharmaceutical companies package their products. By selling drugs in large doses, there is built-in waste. European nations have negotiated distribution of chemo products in smaller doses, which reduces waste and lowers treatment costs. One analyst estimated one-third of all chemotherapy costs in the US are products wasted due to how they are packaged, which means payment one-third more than what is used.
In September, 2017, rather than changing their packaging, Merck responded by CHANGING THE DOSING to a flat 200mg for everyone, regardless of weight, and without clinical evidence of the additional drugs providing benefit, so a football player now gets the same dose as my Irish granny. Instead of selling in 50mg vials, they now only sell in 100mg vials and the clinician is instructed to use two vials, so NO WASTE! If the physician prescribed Keytruda for a 75kg patient according to the previous 2 mg/kg dosing instructions, two 100 mg vials would be used and 50 mg would be discarded. Previously, the 75kg patient would use three 50mg vials and no waste. Experts Peter Bach and Leonard Saltz from Memorial Sloan Kettering Cancer Center estimate this dosing change will result in more than $1 billion per year in extra costs for the U.S. healthcare system for Keytruda. Some countries still receive the 50 mg vials, so there is less waste.
SCREENING AND PREVENTION PROGRAMMES
Both New Zealand the the US are doing more screenings than 10 years ago, though both countries struggle to provide screenings for medically underserved populations.
Mammography
New Zealand
The New Zealand Ministry of Health assesses each district health board (DHB)'s delivery of cancer screenings. For mammography, the target is 70% of women aged 50-69 years have had a screening mammogram in the last two years, including women who may have turned 70 or 71 during the monitoring period. As of January 2018, only four of the 20 DHBs are meeting this target for the medically underserved Māori population, with the performance ranging between 57-77% for this group.
Realizing access is particularly important for the rural poluation, the Ministry of Health set the additional goal of providing mammograms at fixed or mobile sites to ensure travelling time to screening unit:
- 90% of eligible women will be within 60 minutes
- 95% of eligible women will be within 90 minutes
- 99% of eligible women will be within 120 minutes
Mammograms are free for New Zealand residents, ages 45-69. For someone on a work visa, the cost of a mammogram with tomosynthesis in the private setting is $295 ($207 US).
United States
US screening rates vary from 38% (uninsured patients) to 66% (insured patients). The American Cancer Society recommends women start screening annually between 40-45, then every two years for women 55 years and older. The upper age limit for screening is less clear, generally 70-75, but many women over 75 are still having mammograms. Mammograms on this schedule are free under Medicare, and the cost of a mammogram for uninsured patients ranges between $100-148.
Colorectal Cancer Bowel Screening
New Zealand
Like most countries in Europe, last year New Zealand has implemented an organized bowel screening program which involves people aged 60 to 74 years being offered a screening test every 2 years called a fecal immunochemical test (FIT), also known as the "poo test" since a fecal sample is needed to check for tiny traces of blood in their bowl movements, which can be an early warning sign that something is wrong with their bowel. The FIT is a less valuable diagnostic tool because it only detects blood and does not detect a tumor or polyp directly, but it has better compliance since it is far less invasive than a colonoscopy which requires a cleansing prep and minor procedure. In its first year of the program, New Zealand saw a 56% compliance rate with over 300,000 patients, well over the internationally acceptable minimum participation rate of 45% for first screening rounds. And it does not cost that much. In the US, a colonoscopy costs about $2600. The FIT test cost less than 10% of that.
UNITED STATES
In 2015, the American College of Physicians recommended average-risk adults aged 50-75 years should be screened for colorectal cancer by 1 of 4 strategies:
- Poo test (gFOBT or FIT) every year
- Flexible sigmoidoscopy every 5 years
- Poo test every 3 years plus flexible sigmoidoscopy every 5 years
- Colonoscopy every 10 years
Using these options, the American Cancer Society reported 2014 US colon cancer screening rates ranged from 58-76% across all 50 states. However, screening rates in lower income areas, such as those service by Federally Qualified Health Centers (FQHC's) reported the colon cancer screening rates are 38.9%.
RESULTS
What are the outcomes? Three types of cancer are displayed here for the United States and New Zealand. The graph shows 2013 number of cancers and number of deaths per 100,000. Survivor Ratio was calculated to show the effectiveness of treatment. New Zealand has less occurrence in breast and lung cancers, and for all three cancers, New Zealand Survivorship is better.
This is especially remarkable considering the scarcity of oncologists, 72 oncologists for a population of slightly less than 5 million. By comparison, South Carolina has about the same population and over 300 oncologists, plus resources of neighboring states within two hours' drive from its borders. And New Zealand is about three times the geographical size which makes care for remote patients particularly challenging.
Special thanks to all who work in oncology. You are the "Crickets" of this moment!
Two topics mentioned in this article, cost of medications and rural medicine, will be discussed in future blog posts.
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