Despite the rapidly rising global cancer burden, effective treatment continues to remain out of reach for many patients, according to a new study.
In 2015, the World Health Organization (WHO) added 16 new drugs to its list of essential cancer medicines for low- and middle-income countries.
Also for the first time, the WHO included on-patent, high-cost drugs, such as imatinib (Gleevec, Novartis), rituximab (Rituxan, Genentech), and trastuzumab (Herceptin, Genentech), into its Model Lists of Essential Medicines.
However, the researchers found quite a bit of variability as far as which drugs were actually added to national medicine lists, within and between different income groups.
In an analysis published in the Bulletin of the World Health Organization, they found that an average of 3 of the new drugs were added to national medicine lists.
But 33 countries (24%) included at least 10 of these 16 drugs on their national medicine lists, and 21 countries (16%) also included the targeted agents imatinib, rituximab, and trastuzumab.
In fact, almost 20% (26 of 135) of low- and middle-income countries included in the study had already added trastuzumab to their national essential medicines lists before the WHO released its 2015 update.
"We were not surprised with the findings, and we welcomed them as positive and encouraging," said study coauthor Nicola Magrini, MD, secretary, Essential Medicines List, Department of Essential Medicines and Health Products at the WHO.
"As you know, variability is often large and thus expected, whereas the finding that 20% of the countries had already listed trastuzumab or imatinib confirmed our good intention that that is the way ahead and that we should move forward in that direction," Dr Magrini told Medscape Medical News.
However, considering the cost of trastuzumab, Dr Magrini concedes that it was a little surprising that so many countries had added it. "We did ask ourselves that question," he said.
But even though expensive drugs have been added, their accessibility to patients with cancer is yet unknown. "Data on access in terms of how many patients and at what disease stage have access to trastuzumab are not available," he said. "And that is fundamental in order to judge the overall appropriateness of use."
Challenges to Access
The WHO defines essential medicines as those that satisfy the priority health care needs of the population, and the drugs are selected with regard to burden of disease, evidence on efficacy and safety, and comparative cost-effectiveness.
Their list for general medicines is updated every 2 years, but the cancer-specific list has been more sporadic. The most substantial reviews of cancer medicines were conducted in 1984, 1994, and 1999.
For 2015, the 30 cancer medicines currently on the list were retained, and 16 of the 22 proposed new medicines were added. Aside from imatinib, trastuzumab, and rituximab, other drugs added to the list included aromatase inhibitors, bendamustine, capecitabine, cisplatin, oxaliplatin, and trans-retinoic acid.
As previously reported by Medscape Medical News, when the WHO first released the updated list experts had reservations about the ability of limited-resource nations to afford many of these drugs.
Gilberto Lopes Jr, MD, MBA, scientific director of Oncoclinicas do Brasil in São Paulo, had cautioned that this does not mean that these drugs are going to be in every doctor's office next week.
"There are a lot of obstacles in the way," he said during a Global Oncology Symposium Special Session that was held during the American Society of Clinical Oncology 2015 Annual Meeting. "But the challenge begins right now."
Wide Variations Across the Board
Dr Magrini and colleagues note that the level of alignment, in terms of anticancer medicines, between national essential medicines lists and WHO's Model Lists has rarely been investigated.
They point out that a previous review of 76 national essential medicine lists revealed "considerable variation in the listing of anti-cancer medicines by geographical region, socioeconomic status and burden of disease."
In addition, only a few of the lists included the newer targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors.
In this study, they looked at the national medicine lists for 135 countries with per capita gross national income (GNI) below $25,000 in 2015, and they compared these lists with the 2013 and 2015 Model Lists.
Correlations between numbers of cancer therapeutics included in national lists and GNI, government health expenditure, and number of physicians per 1000 population were evaluated.
They found that many of the 25 cytotoxic agents included in the 2013 Model Lists for adults and children appeared on the national medicines lists that were investigated.
Fifty of the countries (37%) each had at least 20 of the medicines on their lists, and, additionally, the lists of 13 countries (10%) included all 25.
Also of note was that at the time this review was conducted, several countries had already updated their national lists to include at least some of the 16 drugs that had recently been added on.
In addition to adding trastuzumab, 50 countries (37%) had placed aromatase inhibitors on their lists, and the national medicines lists of each of 21 countries (16%) listed at least one aromatase inhibitor and trastuzumab.
"This confirms that the revision of the WHO list was long overdue after more than 20 years of limited review of anti-cancer medicines for adults and modest changes to the list of medicines for children in 2011," they write.
But overall, the authors found that the numbers of the new drugs included in national lists were significantly correlated (P ≤ .0001) with per capita GNI (r = 0.45), per capita annual government health expenditure (r = 0.33), and number of physicians per 1000 population (r = 0.48).
As an example, of the 16 new agents, a median of 1 (range, 0 - 10) was included in the national lists of the low-income countries, while the corresponding value for the high-income countries was 10 (range, 2 - 15).
There appeared to be considerable variation between regions, but the authors found that there was actually more variability within regions than between them.
One example was the very low median number of medicines listed in the Western Pacific Region, which turned out to be due to 9 small Pacific Island countries that each included just 2 to 5 cytotoxic agents — often just methotrexate and tamoxifen — on their national medicines lists. When those nations were removed from the analysis, the median number jumped to one closer to that reported for other regions.
Nearly half of the countries had included one or more of the granulocyte colony-stimulating factors in their national medicines lists. These agents are expensive, the authors note in the paper, and even though their use is justified in patients who are at high risk for developing febrile neutropenia, they can be easily overused.
However, Dr Magrini doesn't see this as a great concern. "This is a tiny problem in terms of cost and budget impact in comparison to monoclonal antibodies," he said. "These are manageable drugs that will not bankrupt anyone."
The authors also observed that correlations between numbers of essential medicines and per capita GNI were statistically significant and stronger for the new drugs added to the WHO's list (r = 0.45; P < .0001) as compared with the those on the 2013 list (r = 0.22; P = .0138).
They found a similar correlation for the number of listed drugs and physician density and for per capita government health expenditure.
"International collaboration will be required to manage the prices of cancer medicines better, so that all effective and essential treatments become affordable and available to the millions of patients with cancer, particularly those living in resource-constrained environments," they conclude.
The authors have disclosed no relevant financial relationships.
Bull World Health Organ. 2016;94:735-742. Full text
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Cite this: WHO Essential Cancer Drug List: Out of Reach for Many - Medscape - Oct 21, 2016.