Targeting the Affluent: Differential Access to Targeted Therapies in China

Introduction: Conquering complexity, at a price

Humanity’s war against cancer has seen a radical transformation in recent decades: it is now being fought at a molecular level, harnessing the insights we have gained into the genetic complexity of our enemy[1].

This revolution is coming at a price: the new molecular battlefront is incredibly hungry for money, leading to healthcare costs that are in danger of spiralling out of control. There is, however, inconsistency in different countries’ ability to provide the most effective (read: expensive) drug treatments for their citizens with cancer. Some have a central philosophy of universal access, although this model is becoming increasingly difficult to fund. Others rely on a combination of central and regional insurance to cover part of the costs, with the remainder being paid by the patient. This leads to a significant proportion of the population simply unable to afford the more expensive therapies.

One such country is China. While conditions have been improving thanks to its government’s push for better access to expensive medicines, disparities in income levels continue to drive far-reaching differences in how poorer and richer Chinese cancer patients are treated. Moreover, recent Ipsos data suggest that these differences in access to treatment are ultimately leading to different outcomes for poorer patients.

The Chinese healthcare system: A tale of many cities

China has a complex healthcare reimbursement system, with various insurance systems in play. The Chinese government is trying to integrate these systems and with some success; however, reimbursement coverage in China is still far from universal and can vary widely between provinces.

The total insurance coverage in China increased from <15% to >95% in the period of 2001-2011[2], a remarkable transformation in national health insurance coverage. However, given that the basic social health insurance schemes typically only cover a portion of the total cost, even patients with insurance still pay a significant amount out of pocket for reimbursed drugs. To put some numbers to this, for the 1.31 billion people covered by the China Health Insurance System in 2011, out-of-pocket payments accounted for 73.6% of the total cost of treatment[3].

In this article, we focus on 17 of the top cities in the country[4]: the 3 Tier I cities and 14 cities in the Tier II category. Data are drawn primarily from the Ipsos China Oncology Monitor, a bi-annual pen-and-paper study that collects Real World Evidence from Chinese cancer-treating physicians in these 17 cities. Care should be taken to extrapolate these trends to the full universe of cancer patients in China as the data are sampled from major urban centres so the rural population will be under-represented. For more detail on the study methodology, please download the full paper here.

The Armamentarium’s cost: different classes, different price tags

Cancer drugs can be broadly divided into non-targeted and targeted therapies. The former consist largely of cytotoxic chemotherapies, whereas targeted therapies can be subdivided by their mechanism of action or molecule type. While newer generations of cytotoxics are by no means cheap, targeted therapies are generally more expensive. Large differences in cost per month also exist within the targeted drug therapy category itself.

Lung cancer:  same mutations, treated differently based on income

EGFR inhibitors, which target EGFR mutations (particularly common in patients of Asian ethnicity[5]), are now a key part of the treatment approach for non-small cell lung cancer. Several different brands are available in China at wildly different price points – from Yiruike (a local gefitinib brand) at ¥2,000 per cycle to Tagrisso (osimertinib) at ¥51,000 per cycle.

The graph below shows the use of selected EGFR inhibitors amongst patients with different income levels by oncologists in Ipsos’ China Oncology Monitor panel:

2017 data show that the patients in our study with a monthly household income of less than RMB 7,000 are significantly less likely to be prescribed EGFR inhibitors than patients with a monthly household income of over RMB 10,000. The former are more likely to be prescribed non-targeted cytotoxic chemotherapies, which are generally cheaper but less efficacious, for the treatment of EGFR-mutated NSCLC[6]. One notable exception is icotinib; until 2016, the lower-income patients in our survey were more likely to be treated with this less expensive targeted product than the higher-income segment.

Metastatic colorectal cancer: add-ons for the rich

By projecting Ipsos’ data, we estimate that metastatic colorectal cancer (mCRC) in the 17 cities of focus has a drug-treated prevalence of approximately 51,000 patient treatments per year. The data suggest that the uptake therapies for mCRC has been relatively modest in China, although differences based on patients’ income levels are particularly obvious here:

As illustrated, the mCRC patients in our 2017 survey with a high monthly income were significantly more likely to be prescribed bevacizumab than those in the lower income bracket. Cytotoxic regimens such as FOLFOX, in combination with a VEGF inhibitor or an EGFR inhibitor, are generally considered to be the standard of care for first line metastatic colon cancer patients[7] who can afford it. Poorer patients would still be able to benefit to some extent from cytotoxic-only regimens without the addition of bevacizumab, which is prescribed to the more affluent patients to further increase the efficacy of their chemotherapy regimen[8].

Tying it together: household income appears to be strongly related to cost of therapy

The previous examples highlighted that the patients in our study with lower household incomes are less likely to take targeted therapies. We also know that these targeted therapies are more expensive; it is therefore to be expected that the total cost of anti-cancer drug therapy per cycle is markedly lower for our study’s poorer patients:

The median cost of NSCLC drug therapy per cycle of RMB 10,000-19,999 compares to a per capita disposable income (2016) of just over RMB 4,800 per month in Shanghai, and <RMB 3,000 per month in most Tier II cities[9]. One cycle of drug therapy is therefore far more expensive than the amount patients in China earn per month.

According to our data, almost half the lowest income patients are treated with regimens that cost less than RMB 10,000 per cycle, compared to under 25% of patients in the highest income bracket; doctors in the 17 major cities of focus tend to reserve these regimens for patients unable to afford more expensive treatments. Nearly 30% of patients in the highest income bracket are prescribed regimens that cost over RMB 20,000 per cycle, compared to under 10% of patients on low incomes.

Lower-income residents of the major cities in China are clearly less likely to receive more expensive treatments for their cancers – but is this lower cost of therapy also leading to poorer outcomes?

Cost and outcomes

ECOG performance status reflects cancer patients’ overall wellbeing. The chart below, again based on Ipsos data, shows the ECOG score at the time of the most recent doctor visit, for multiple myeloma patients currently on anti-cancer therapy, by income levels:

The patients with income levels above RMB 7,000/month are significantly more likely to have an ECOG status of 0-1; in other words, a larger proportion of affluent drug-treated myeloma patients in the Ipsos data are doing better overall than their less affluent counterparts. While we cannot exclude other factors playing a role in this correlation (e.g. access to better healthcare overall), it is likely that the higher usage of targeted drug therapies is part of the reason.

Somewhat paradoxically, there is also a higher percentage with a score of 3-4 in the affluent group of patients in our database. Because ECOG 3-4 patients generally cannot tolerate cytotoxic chemotherapies, many of these will simply not have any treatment options – unless they can afford targeted therapies with fewer toxicities.

Another outcomes-related metric is the average number of cycles received during the first metastatic line before disease progression, shown here by income levels.

Patients in the lowest income brackets in our sample often only stay on their 1^st line for just 1-3 cycles prior to a switch due to disease progression, whereas a significant proportion of more affluent patients stay on therapy for 7+ cycles. This indicates a direct relationship between progression-free survival and income levels in this population.

Conclusion

The recent revolution in our war against cancer has not bypassed China: here, too, targeted therapies are increasingly used in Tier I and Tier II cities. However, our data suggest that a large swathe of the urban population is unable to benefit from these advances, simply because they cannot afford the latest therapies. Not only is this leading to a different treatment landscape for patients in high vs low income brackets, it is also having a tangible impact on their respective outcomes. If you’re a cancer patient in China, you are more likely to do better if you’re rich, despite the existence of national and regional insurance programmes.

We should not forget, however, that anti-cancer treatment in China has come a long way. Going back 10 years, hardly any of the patients in our database – rich or poor – were treated with targeted therapies. The push towards better treatment had to start somewhere, and it is not surprising that it was the higher income group that was the first to benefit from this.

Importantly, the National Health Commission in China is continuing to make efforts to address the affordability concerns by implementing further price reductions for anti-cancer drugs, through centralized negotiations and procurement. One such round of price cuts was announced by the NHC in July 2018[10], shortly after the Ministry of Finance decided to exempt several drugs from import tariffs. This may lead to an influx of more affordable drugs from markets such as India. Biosimilars – both local and international – are also likely to see significant growth in the near future.

These steps are clearly necessary: the sales of anti-cancer medicines in China already exceed an estimated RMB 120 billion per year[11], despite only a small percentage of the population currently having access to the more expensive cancer therapies. Clearly, treating the majority of eligible Chinese cancer patients with targeted therapies would lead to a staggeringly high total spend, unless the average cost per cycle of these innovative drugs comes down considerably.

We started this article by stating that the war against cancer is undergoing a remarkable revolution; a significant proportion of the population in China is unfortunately likely to miss out on this revolution due to simply not being able to afford the latest molecular tools and drugs. However, if long-term efforts continue to be made to address this affordability gap, we can hold on to the hope that one day, every single patient in China – and indeed the rest of the world – will be able to conquer their cancer.

Pieter De Richter is Head of Real World Evidence, APAC & MENA, at Ipsos.

About the research

Drug treatment patterns discussed in this paper were investigated using the Ipsos Global Oncology Monitor^©, a patient record database. A panel of cancer-treating physicians – screened for specialty, level of seniority and status as the main treatment decision-maker – reported on drug-treated cancer patients seen in consultation during the study period. Sample data were then projected to the wider clinical population. Data were collected online and through pen and paper diaries. Data are copyright Ipsos 2018, all rights reserved.

[1] De Richter, P. “Harnessing Complexity: Companion Diagnostics in Oncology”, 2nd edn. Ipsos Healthcare, 2017

[2] National Health and Family Planning Commission of China: China Statistics Yearbook of Health and Family Planning 2013. Beijing, 2013

[3] Zhang, Y et al. “National Health Insurance Development in China from 2004 to 2011: Coverage versus Benefits.” PLoS ONE 10(5): e0124995, 2015

[4] As ranked by population: Beijing, Shanghai, Guangzhou, Chongqing, Hangzhou, Wuhan, Chengdu, Tianjin, Xi’an, Jinan, Nanjing, Shenyang, Harbin, Fuzhou, Zhengzhou, Changsha, Shijiazhuang

[5] Shi, Y et al. “A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)”. J Thorac Oncol.; 9: 154–162, 2014

[6] Treviglio-Caravaggio, AO et al. “Efficacy of EGFR Tyrosine Kinase Inhibitors in Patients with EGFR-Mutated NSCLC: a Meta-Analysis of 13 Randomized Trials”. Clinical  Lung  Cancer; 13.2: 107-114, 2012

[7] Yoshino, T. et al. “Pan-Asian Adapted ESMO Consensus Guidelines for the Management of Patients with Metastatic Colorectal Cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS.” Annals of Oncology 29: 44-70, 2018

[8] Jang, Hyun Joo et al. “The Addition of Bevacizumab in the First-Line Treatment for Metastatic Colorectal Cancer: An Updated Meta-Analysis of Randomized Trials.” Oncotarget 8.42: 73009–73016, 2017

[9] National Bureau of Statistics of China

[10] http://en.people.cn/n3/2018/0702/c90000-9476612.html

[11] “Cancer Drugs in China: Affordability and Creativity.” Editorial, The Lancet 391: 1866, 2018