Barriers to Immune Checkpoint Inhibitor Access for Patients With Cancer in Southeast Asia: Challenges and Policy Implications

Introduction

Cancer is a leading cause of morbidity and mortality in Southeast Asia (SEA), a region of over 690 million people.¹ Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors (ICIs) being the most widely used.^2,3 ICI agents have become integrated into clinical guidelines for cancers such as some kinds of non-small cell lung cancer (NSCLC), breast cancer, and melanoma.³ Yet, in low-resource settings across the globe like many parts of SEA, access to ICI remains limited.⁴ Vast disparities in the region's health care infrastructure, economic resources, and health care delivery have rendered ICI inaccessible to most.⁵ We use the lenses availability, affordability, accessibility, acceptability, and accommodation to illustrate factors that contribute to disparities in ICI access in SEA and propose potential solutions.⁶

Factors Contributing to Disparities in ICI Access

Availability

SEA continues to face shortages of health care personnel, particularly in resource-poor countries like Laos, Cambodia, and Timor-Leste, because of limited training and employment capacities.^7,8 This limits the availability of multidisciplinary professionals who manage immunotherapy centers.^5,9 By contrast, high- and upper-middle–income countries with greater health care resources such as Singapore and Thailand have made ICI available in their national cancer care programs.⁵ However, essential diagnostics such as molecular pathology services and next-generation sequencing platforms remain largely unavailable to many.⁷

Common to most countries in SEA is the urban concentration of cancer care facilities, leaving rural areas largely underserved.⁵ In the Philippines, only the National Capital Region has at least one medical oncologist per 100,000 people; all other regions fall short.⁹ In Indonesia, limited provider coverage and bed capacity in remote provinces have led to high treatment migration rates to urban provinces for cancer care, representing 8% of total cancer care.¹⁰ In addition, outdated cancer registry databases hinder effective planning and equitable resource distribution.^5,9

Accessibility

The geography of countries in SEA poses a significant barrier for equitable cancer therapy delivery and, by extension, ICI.⁵ Thailand, with a contiguous land mass, has a relatively uniform distribution of cancer services supported by a comprehensive referral system and strategically placed tertiary centers.¹¹ By contrast, patients in archipelagos such as the Philippines and Indonesia still face fragmented health care systems with cancer care services centered around urbanized, high-income regions.^9,12 In countries such as the Philippines, this distribution has resulted in a highly centralized model, causing patients from more rural areas and Indigenous peoples to have to travel long distances—often at considerable financial burden—for advanced care such as ICI, often outpacing earning capacity.^5,13

Affordability

At the center of these barriers is the prohibitive cost of ICIs. Without robust health financing systems and comprehensive universal health coverage (UHC), access remains restricted to a small fraction who can afford to pay out of pocket or who have comprehensive private health insurance.¹⁴ With an estimated annual cost of $150,000 US dollars (USD) to $200,000 USD for ICI medications, lower-income households either have no access or face catastrophic economic consequences if they attempt to pay out of pocket.¹⁵ Some countries like Thailand have expanded health care coverage to include ICIs; however, these are limited to a specific subset of patients where ICIs are used as the second- or third-line agent.¹⁶ There are also no quality-assured generics or biosimilars in the region because of active patents.¹⁷

Acceptability

Intersectional disparities persist across SEA influenced by race, ethnicity, sex, and socioeconomic status.⁵ Cultural values shape health care decisions about novel therapeutics and end-of-life care.^18,19 A Singapore study found that cultures rooted in dispositional pessimism exhibited higher cancer fatalism, reducing uptake of cancer screening and therapy acceptance.²⁰

Religion also influences cancer therapy acceptability. Beliefs in predetermined life and an inevitable destiny—common to many SEA religions—may limit patient engagement in planning decisions around end-of-life care.¹⁸ Because ICI has been shown to prolong overall survival (OS),³ ICIs may be viewed ambivalently in religious contexts, potentially seen as prolonging suffering, disrupting the natural order, and interfering with necessary karma, a concept common in many SEA belief traditions.^5,18 Such beliefs, however, must be understood in the contexts of resource limitations and should nuance but not dictate shared decision making.^18,20

Concerns about ICI's side effects further reduce acceptability.¹⁹ Trials for anti PD-1 and PDL-1 inhibitors for patients with NSCLC found that Asian populations experience higher adverse events for any-grade (84%-97%) and grade 3 to 4 (22%-44%) cancers compared with White cohorts, contributing to discontinuation.²¹ While differences in epidemiology, genetic susceptibility, and molecular profiling among Asian patients with lung cancer have been postulated to contribute, studies in the region are lacking and current data remain inconclusive.²¹

Accommodation

Barriers to advanced cancer therapy in SEA often arise from poor integration of cancer services.⁵ Among low-middle–income countries in the region, multidisciplinary care that is required for ICI remains limited because of geographic constraints, inadequate access to technology, inefficiency of communication channels, and insufficient staffing.^5,8 While Singapore has decentralized cancer services through satellite NCID on the go clinics—community-based cancer clinics that decentralize care and make ICIs more accessible²²—other SEA countries lag behind.

Another compounding problem in the region is the lack of clinical studies for ICI. The genomic drivers of patients with cancer in SEA still remain poorly understood, hindering the development of population-specific management strategies.^23,24

Across SEA, barriers are shaped by differences in health care infrastructure, economic constraints, and regulatory policies. Although overall access remains low, examination of individual countries highlights unique challenges and solutions. In Malaysia, conventional cancer therapies such as chemotherapy and radiotherapy are covered under the country's UHC system. However, since ICI is not included, clinicians often rely on alternative strategies, enrolling patients in clinical trials or applying for pharmaceutical companies' patient assistance programs (PAPs).²⁵ In Thailand, the lack of coverage from government insurance policies restricts ICI access.¹⁶ In Vietnam, minimal reimbursement schemes have made ICIs available to <1% of eligible patients.²⁶

Points of Action and Recommendations

Navigating Financial Barriers Through Dose Optimization

To address financial barriers, physicians have found innovative strategies to reduce treatment costs and improve access through dose regimen optimization.²⁷ In Malaysia, clinicians have explored dose reduction strategies for ICIs, supported by Korean studies that have demonstrated comparable survival outcomes with low-dose nivolumab compared with standard dose in patients with NSCLC.²⁸ A trial in India among patients with advanced head and neck cancer demonstrated that ultralow-dose nivolumab (6% standard dose) improved survival outcomes when added to standard treatment at a dose of 20 mg flat dose, once every 3 weeks while reducing costs to merely 5%-9% of the full regimen.²⁹

In Singapore, a study among patients with advanced NSCLC found that pembrolizumab at a lower dose of 100 mg flat dose, every 3 weeks (Pem100) compared with the standard 200-mg flat dose, every 3 weeks (Pem200) showed no difference in progression-free survival and OS alone or when combined with chemotherapy with no difference in response rates or immune-related toxicities.³⁰ A cost minimization analysis estimated a cost saving per patient of SGD 39,942 ($30,457 USD) for the Pem100 group.³⁰ Another Indian study for patients with microsatellite instability-high advanced colorectal adenocarcinomas also reported similar efficacy with low-dose nivolumab.³¹ In Malaysia, a small-scale trial demonstrated that low-dose nivolumab as salvage for NSCLC can be as effective as standard regimens.³²

Other cost-saving strategies include shortened treatment durations or alternate-day dosing. While regional studies are limited, global studies show promise. A French multicenter trial in unresectable stage III or IV melanoma found that discontinuing ICIs at 12 or 18 months showed no significant impact on long-term survival compared with continuous treatment.³³ Notably, discontinuation at 24 months improved outcomes, showing a 10.5% higher 48-month survival rate and a modest gain in survival time.³³ However, these strategies must be contextualized by cancer type. A study among patients with NSCLC who continued ICIs beyond 6 and 12 months had significantly longer PFS (22.8 v 11.8 months and 27.9 v 14.8 months) and OS (33.9 v 14.4 months and 39.7 v 18.0 months) compared with earlier discontinuation—indicating that this strategy may not be suitable for all cancers.³⁴

Neoadjuvant ICI has shown promise across early-stage cancers. The KEYNOTE-671 trial among patients with early-stage NSCLC demonstrated that adding pembrolizumab to chemotherapy significantly improved event-free survival (62.4% v 40.6%) and major pathologic response (30.2% v 11.0%).³⁵ Similarly, in stage II–III triple-negative breast cancer, a pooled analysis of randomized controlled trials revealed that neoadjuvant ICI combined with chemotherapy significantly improved survival outcomes.³⁶ While these support neoadjuvant ICI in select cancers, they also highlight the need for predictive biomarkers to guide patient selection³⁷—research that remains sparse in SEA.

Future Research

Clinical research must focus on evaluating ICI's effectiveness in the diverse populations of SEA.³⁸ More countries in the region should conduct locally driven clinical trials exploring dose optimization strategies—such as low-dose regimens, alternate-day dosing, and neoadjuvant ICIs—in the context of the unique genomic epidemiology of SEA populations. Integrating these optimization strategies in future guidelines will expand access to life-saving treatments for patients who otherwise face financial catastrophe or forgo care altogether because of cost.³⁹ A parallel focus on characterizing the population-specific toxicity profiles is also needed, in addition to greater global representation in ICI clinical trials.

Future research into creating biosimilars should also be conducted. Governments should partner with private industries to promote the creation of biosimilars and generics, which would lower cost, especially with the upcoming patent expirations for several key ICIs like pembrolizumab and nivolumab.¹⁷ The creation of these biosimilars has the potential to significantly expand access to ICI in resource-constrained settings. In Malaysia, the introduction of trastuzumab biosimilars has led to notable improvements in survival among patients with human epidermal growth factor receptor 2–positive breast cancer, offering a glimpse of what might be possible for ICI therapy once biosimilars become available.⁴⁰

Clinical Settings

To address the clinical barriers hindering ICI access in SEA, a patient-centered approach must be prioritized. Integrating patient navigators improves care continuity and reduces dropout rates, especially in fragmented systems.⁵ The Philippines ICanServe Foundation exemplifies how civil society can bridge awareness gaps by guiding patients toward financial aid, government support schemes, and nonprofit programs.⁴¹ Structured education on ICIs, especially around adverse effect management, can empower patients and improve treatment adherence. Electronic patient-reported outcome measures may effectively monitor AEs and can potentially decrease treatment discontinuation.¹⁹

Cancer Policy

Recognizing the deeply rooted cultural contexts of SEA populations should guide the development of future ICI programs.^13,42 These programs should include patient-level interventions—such as counseling, supportive care, and resource navigation—to improve treatment acceptance and adherence by alleviating psychosocial and financial barriers.³⁸ Creating tiered access programs for patients meeting well-defined evidence-based criteria can help governments optimize resource allocation and ensure increased ICI access for patients who will most likely benefit, while reducing the risk of financial catastrophe. Robust financial navigation systems may help leverage available financial assistance programs for ICI from the government, nongovernment organizations, pharmaceutical companies (PAPs), and other stakeholders.

At the health system level, countries should develop unified structures for ICI that increase coordination across all levels of care. Professional societies and academic institutions must maximize the utility of ICI while balancing cost-effectiveness, amid the rapidly evolving landscape of cancer treatment. Inclusive and updated guidelines for delivering access to ICIs across health care sectors are essential.

Governments in SEA should explore collaborative mechanisms like pooled procurement agreements. For example, The National Cancer Grid in India is a network of cancer institutions that have successfully negotiated with pharmaceutical companies to secure reduced prices for cancer drugs.⁴³ Regional alliances in SEA could adopt these strategies to negotiate lower prices and advocate for tiered pricing from pharmaceutical companies that reflect resource variability across countries.^38,44 Countries can also collaborate with international groups, foster regional alliances such as with the Asia Pacific Oncology Drug Development Consortium,⁴⁵ and produce domestic alternatives, such as in similar resource-limited countries in the Middle East.⁴⁶

Movements toward improving access to ICIs have become apparent in recent years. In Singapore, atezolizumab and pembrolizumab are now subsidized under the medication assistance fund.⁴⁷ In Vietnam, the Ministry of Health through the FV Hospital in Ho Chi Minh City has offered programs that subsidize ICIs.⁴⁸ Thailand has established the Thailand Hub of Talents in Cancer Immunotherapy to promote hospital-based cancer immunotherapy research. Indonesia has approved the development and use of serplulimab, a Chinese-made anti-PD1 monoclonal antibody for treatment of extensive SCLC, which has been shown to be a more cost-effective option than standard nivolumab, pembrolizumab, and ipilimumab.⁴⁹ In the Philippines, the creation of the National Integrated Cancer Control Program Strategic Framework promises to improve access to cancer centers and provide financial support for patients but still underprioritizes ICIs.^50,51

In conclusion, future ICI programs in SEA must adopt a proactive and multipronged approach. Addressing cost concerns, promoting education, and encouraging technology transfer may enable wider availability and utilization. Similarly, efforts to decrease red tape and bureaucracy associated with domestic ICI production are needed. Stronger collaboration in the Asia Pacific region is needed to create guidelines that fellow countries can adapt or reference. With coordinated efforts, SEA countries can work together to ensure equitable access to ICI for patients with cancer.

AUTHOR CONTRIBUTIONS

Conception and design: Adrian E. Go, Frances Dominique V. Ho, Frederic Ivan L. Ting, Edward Christopher Dee

Financial support: Edward Christopher Dee

Provision of study materials or patients: Chaiyut Charoentum

Collection and assembly of data: Adrian E. Go, Puneeth Iyengar, Nur Fadhlina Abdul Satar

Data analysis and interpretation: Adrian E. Go, Erin Jay G. Feliciano, Puneeth Iyengar, Imjai Chitapanarux, Chaiyut Charoentum, Nirmala Bhoo-Pathy

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.

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