A potentially lifesaving or life-extending breast cancer medicine is available to public sector patients in several provinces, but not in the Western Cape.
The drug, trastuzumab, has often been in the headlines over the last decade.
For several years, activists campaigned to have the price reduced and the Competition Commission earlier this year announced it was seeking to prosecute pharmaceutical company Roche for alleged excessive pricing of the drug.
Trastuzumab is used to treat a specific subset of breast cancers called HER2 positive (HER2+).
It is given in addition to other cancer treatments like chemotherapy and radiation and has been shown to significantly reduce the chance of the cancer recurring after treatment.
It is administered either through an IV or subcutaneously.
The drug had been listed on the South African Essential Medicines List (EML) since 2017, according to this timeline document compiled by the Cancer Alliance (a local advocacy group), and is currently only approved for early-stage HER2+ breast cancer.
After its listing on the EML, trastuzumab should have theoretically been made available in all the provinces that have treatment centres for cancer that are linked to academic hospitals.
Trastuzumab was listed on the World Health Organisation's Essential Medicines List in 2015.
Access to the drug in the public sector in South Africa has been something of a lottery, depending on where you live.
Public sector oncologists in the Northern Cape had successfully motivated for the necessary budget to provide trastuzumab at the Kimberly Hospital as early as 2011.
The Cancer Alliance's timeline stated the Department of Defence was using trastuzumab in military hospitals in 2013.
According to Dr Mathabo Mathebula, the CEO of Steve Biko Academic Hospital in Gauteng, the drug had been provided in the province since 2017.
A doctor from the Free State told Spotlight the province started prescribing the drug to patients in November 2018.
History of trastuzumab in SA
The project manager for the Cancer Alliance's Access to Medicine Campaign, Salomé Meyer, told Spotlight trastuzumab had been made available in Gauteng, the Free State, KwaZulu-Natal, the Northern Cape, and Eastern Cape, although the Eastern Cape might be experiencing procurement problems.
According to Meyer, the Western Cape Department of Health had never procured the drug. This, she said, had forced some patients to pay for their own treatment or simply go without.
"Since 2017, the Western Cape has refused to provide trastuzumab treatment for women with early [HER2+] breast cancer," she added. "If it was for one year, it's a different story, but this has been going on for five years."
This was confirmed by Professor Paul Ruff, Emeritus Professor and former head of medical oncology at the School of Clinical Medicine in the Faculty of Health Sciences at the University of Witwatersrand. He held the title from 2002 until 2021.
While he said he could not be sure of exactly what the case was for all the other provinces in the country, when it came to patients being able to access trastuzumab for HER2+ early breast cancer, it was being routinely used in Gauteng.
The Western Cape is the only province that has been systematically restricting access to the medicine by outright refusing to procure it for its patients.
According to Ruff, the national Department of Health mandated what was on the Tertiary/Quaternary Essential Medicines List (TQEML) via its National Essential Medicines List Committee (NEMLC) and which medicines were on national tender, but that each province procured its own medicines using the budget assigned to it by National Treasury.
He said the Constitution allowed each province significant autonomy when it came to healthcare provision.
Ruff added trastuzumab had only been approved for use in South Africa for those with early-stage HER2+ breast cancer, although the medicine was widely used in the private sector as well as in many countries for advanced HER2+ breast cancer.
He said trastuzumab had been the standard of care in early breast cancer in most countries for more than 15 years.
Meyer added research in South Africa had shown around 26% of women with breast cancer were HER2+, which translated into a small population within the greater breast cancer population.
But for them, she said, trastuzumab could be a lifesaving treatment that could extend their lives.
"Women are not equitably getting that treatment and not treated equally," added Meyer. "Women in the Western Cape do not receive equal treatment [compared to] their sisters in other provinces. Are we then saying that their lives are not important enough?"
Trastuzumab remains 'unaffordable'
Spotlight received a written comment from the Western Cape government's Health and Wellness' provincial pharmacy and therapeutics executive committee.
In its response, the committee confirmed the province did not procure trastuzumab and it (the Health and Wellness' provincial pharmacy and therapeutics executive committee) made decisions on what medicine were procured in the province.
"Consultation with the operations executive committee meeting occurs for medicines which will have substantial impact on services or cost and budgets," the response reads.
"The price of trastuzumab remains unaffordable. Although the national Department of Health included trastuzumab on the Essential Medicines List, no additional funding was made available to procure this medicine.
"The tertiary hospital budgets are fully allocated and additional funding is required for trastuzumab. The budget for oncology medicines is spent fully each year and either additional budget or lower prices are required to procure trastuzumab," the committee said."Despite the improved outcome in a small subset of women, the cost remains unaffordable and an unfunded mandate. Unless additional funding is made available to oncology centres, trastuzumab remains unaffordable."
Trastuzumab was first approved by South Africa's medicines regulator in 2001 under the brand name Herceptin®.
Roche, the pharmaceutical company that produces and markets Herceptin, also received approval in 2012 for Herclon®, essentially the same product sold under a different name.
A search of the SA Health Products Regulatory Authority's registers shows versions of trastuzumab made by pharmaceutical companies Mylan and Adcock Ingram were approved in 2019 and 2020, respectively.
Meyer said the price of trastuzumab had gone down significantly in the last few years.
In 2017, she added, only the originator product, Herceptin®, and its clone product, Herclon®, were available globally.
Other biosimilars for Herceptin became available in 2019, which caused the price of trastuzumab to come down.
Since trastuzumab is a biologic medicine, versions of the drug made by companies other than Roche (the originator) are referred to as biosimilars rather than generics.
According to the Cancer Alliance's Timeline on trastuzumab, in July 2017, prior to it being on the national tender, Roche agreed to supply Herclon® to the national Department of Health for R117 569 per recommended 17-18 cycles (given over 12 months) each patient should receive.
This translates to about R6 531 per treatment cycle.
However, Ruff said once it was put to tender in 2018, Herclon's cost was reduced to about R6 500 per cycle.
He added consequent tenders in 2020 were given to Mylan, for the biosimilar Ogiviri® which cost R4 978.36 per injection according to the 2021 Master Product List.
On the current (2022) Master Product List, Cipla South Africa Medpro is listed as supplying Cipla Trastuzumab® at R3 450 per 440mg injection.
Evidence of effectiveness
Ruff said there was a large body of evidence around the effectiveness of trastuzumab in patients with early HER2+ breast cancer, which the Western Cape Department of Health appeared to have disregarded.
Results from four major international studies conducted in patients with HER2+ early breast cancer over 15 years ago, including the BCIRG-006 and HERA trials, in which South Africa participated, all showed trastuzumab could significantly reduce the risk of a patient's HER2+ breast cancer reoccurring, he added.
He said when it came to risk reduction, studies described both a relative reduction and an absolute reduction.
The four clinical studies on trastuzumab all showed about a 40 to 50% relative reduction in risk of cancer progression and between 5 and 8% absolute reduction, both of which in the cancer context is significant.
One year of treatment with trastuzumab (which was 17-18 cycles of treatment) used to be the accepted standard but had now been reduced to six months (now 8-9 cycles of treatment), according to Ruff.
This was based on a review published in the SA Medical Journal in 2020.
This should bring the price down even further as patients do not need as many treatments as before, going from 18 to nine treatments.
The implications of the Western Cape Department of Health declining to procure trastuzumab were far-reaching, said Ruff.
"By denying access [to trastuzumab] you are denying access to a treatment that can … prolong survival and potentially cure a reasonable subset of breast cancer patients," he added.
"We live in a resource-constrained environment. We know that it's always better to spend our money on treatments that can cure people rather than treatments that are going to give patients only [a] few extra months [of] survival," he said.
"We always push harder when you have treatments that are curative, which this is [for a subset of about 25% breast cancer patients]… It's aimed at curing patients who then can lead a normal life as opposed to having their cancer coming back."
At what cost?
However, the Western Cape committee said the benefit of trastuzumab for some patients would come at the cost of other cancer services if implemented.
"The benefit comes at an additional cost that is not affordable. This cost would be in addition to the cost of chemotherapy, surgery, radiotherapy, and endocrine therapy currently provided.
"It is an unfunded mandate and use will therefore be at the expense of other interventions, for example, radiological equipment to treat cancer or other medicines to treat other cancers, " it added.
By unfunded mandate, the committee said it meant: "It is an unfunded mandate in that no additional money was provided by National Treasury in liaison with the national Department of Health to make provision for the procurement of trastuzumab."
According to it, trastuzumab would be considered in the Western Cape if there was "a significant further reduction in price as well as an increased capacity to administer in oncology units".
A patient's perspective
Meanwhile, whether or not one accepts the trade-offs made by the Western Cape Department of Health and Wellness, the impact of these procurement decisions on women with HER2+ breast cancer is all too real.
*Jane Smith, a general practitioner, spoke to Spotlight on behalf of her mother who in 2019 at the age of 69 was diagnosed with HER2+ breast cancer.
Smith said she was initially confused by the treatment plan offered to her mom by Groote Schuur Hospital, which included chemotherapy, excising the lump, and chemotherapy again.
She was confused because it made no mention of using trastuzumab as she knew studies have shown it can significantly reduce the risk of this kind of cancer recurring.
"HER2+ cancer is quite an aggressive cancer, so it's one that would come back. And so, without the Herceptin [trastuzumab] the chances of it coming back were good.
"The reason why the Herceptin was important was so that we can prevent it from returning and therefore give her a better quality of life and hopefully give her a longer life."
She then started looking at the options available to get trastuzumab included in her mother's treatment.
After phoning two cousins who work in hospitals in Kimberly and Johannesburg, Smith was informed if her mom was living in either of the provinces, trastuzumab would in all likelihood be provided to her.
"Obviously we were devastated, and we looked for options in Cape Town for her to get it," she said.
With no other viable options to be found, Smith and her family had to finance the trastuzumab themselves, starting with six months of treatment with Herceptin and six months of treatment with Ogiviri.
"My family and I, we put basically all our savings, all the money that we had to give my mom the medication," she said. "We don't have a wealthy background … and truthfully, it essentially bankrupted us."
Smith estimated the treatment cost her family about R135 000, as they did nine cycles of treatment with Herceptin at about R10 000 per treatment and another nine sessions of Ogiviri at about R5 000 per treatment.
Besides the financial burden, she had to arrange for her mom to receive the treatment at Groote Schuur Hospital and collect the treatment from the pharmacy herself.
All doses, with the exception of the first one which was ordered and collected at a nearby Dischem, were purchased from the pharmacy at the UCT Private Hospital (located next to Groote Schuur).
Smith had to take off work on the day of her mother's treatment, collect the drug from the pharmacy, and take it to the oncology wing so it could be administered to her mother. All of which were complicated by the strict Covid-19 restrictions that came into effect in 2020.
She said it was incredibly stressful as she was always worried something would go wrong and her mother might not get the drug on the day she needed it, and she lost income on treatment days - income she needed to help pay for the next doses.Smith's mother has since gone into remission and is currently being monitored with regular mammograms.
Access in the private sector
But it's not just patients in the public health sector in the Western Cape who have struggled to access trastuzumab.
Some patients with private medical scheme coverage have also struggled to access it, especially prior to 2020.
Since then, trastuzumab has been included as a preferred minimum benefit (PMB) for some but not all HER2+ breast cancer patients diagnosed with early-stage breast cancer.
This means that for women who meet the eligibility criteria set out in the PMBs, medical schemes are now compelled to pay for the drug.
"What we did as the Cancer Alliance, we successfully pushed the Council for Medical Schemes to change the prescribed minimum benefits. Because the principle is what is provided in government, in public [healthcare sector] must be provided in private. It took them two years to in fact approve trastuzumab as a PMB," said Meyer.
In September 2017, Justine McKinnon was 30 years old and went for a mammogram due to a family history of breast cancer.
It came back negative but by December of that year, she had a lump in her breast and was subsequently diagnosed with stage three HER2+ breast cancer. At the time, she lived in the Western Cape.
McKinnon started treatment in May 2018 and was informed by her oncologist that she should fight to get her medical aid to provide her with trastuzumab in addition to her other treatment, which she said her medical aid declined to do.
She then contacted the Cancer Alliance where Meyer informed her trastuzumab was not available in the public healthcare sector in the province either.
Meyer said if McKinnon’s cancer had manifested in 2020 instead of 2017, her medical aid would have covered trastuzumab as a PMB.
Despite this setback, McKinnon said she was adamant she would fight to get the treatments that would give her the best chance at survival.
"Sometimes you need to do your homework really extensively to know that this is your life. And no one else is going to do it for you. You need to get what you need to survive."
She then had to fund the first four treatments of trastuzumab herself while struggling through the effects of chemotherapy and radiation and an eventual lumpectomy, with the help of family members.
"You don't know how strong your fight has to be," McKinnon said about needing to advocate for a lifesaving treatment while also dealing with a cancer diagnosis.
She was eventually able to upgrade her medical aid to a plan that would pay for the rest of the trastuzumab she needed.
But before that, she had to pay more than R19 000 per treatment, totalling around R76 000 overall. She finished treatment in 2019, a year before trastuzumab's inclusion as a PMB.
While she said she was lucky, McKinnon added there were people who were not in a position to finance this treatment and were thus denied access.
"I was denied Herceptin and I'm still here to tell the story. There are women that can't tell their stories. There are children that have lost their mothers because they were denied trastuzumab," she said.
"In a country with such violence and such hardships, why make it more complicated?" she asked. "It's a game changer [trastuzumab] – it's a game changer."
*Jane Smith is not her real name
NOTE: SECTION27 and the Treatment Action Campaign have been involved in trastuzumab-related advocacy. Spotlight is published by SECTION27 and the Treatment Action Campaign but is editorially independent - an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.