Expert recommendations for biomarker evaluation of advanced non-small cell lung cancer in Thailand

Introduction

Lung cancer is the most common cancer and the most common cause of cancer death worldwide (1). In Thailand, it is the second most diagnosed cancer and the leading cause of cancer deaths after liver cancer (2). Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for approximately 85% of the cases of lung cancer (3,4). Between 1997 and 2001, the 1- and 3-year survival rates for NSCLC in Thailand were 28.9% and 3.3%, respectively (5); these survival rates improved to 37.8% and 15.1%, respectively, between 2013 and 2017 (6). Alarmingly, it has been shown that patients with lung cancer in Thailand primarily present with late-stage disease (5-9).

With growing understanding of the heterogenous molecular profiles of NSCLC, the treatment landscape for advanced NSCLC has moved towards precision medicine, guided by the presence of actionable target gene alterations (3). For instance, the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) targeting EGFR mutations has led to a paradigm shift in the treatment of patients with advanced NSCLC, and EGFR TKIs are now recommended as first-line therapy for EGFR mutation-positive advanced NSCLC (10,11). In a recent retrospective analysis of patients with locally advanced/recurrent NSCLC at Ramathibodi Hospital in Thailand, 56.3% of patients tested positive for EGFR mutations, and these patients survived significantly longer when treated with EGFR TKIs compared with those who were EGFR mutation-negative and did not receive treatment with EGFR TKIs (mean overall survival: 36.4 vs. 11.9 months, P<0.001) (12). Other studies in Thailand have also highlighted the efficacy of EGFR TKIs in EGFR mutation-positive advanced NSCLC (13-15).

The global clinical development and approval of various molecular targeted therapies and novel immunotherapy targeting EGFR, ALK, KRAS, RET, MET, BRAF, NTRK, and ROS-1 as well as anti-PD1/PD-L1 and anti-CTLA4 molecules, has necessitated a range of predictive and prognostic biomarker tests for the identification of specific molecular features to provide personalized cancer therapy (3,4). As such, international guidelines for biomarker testing in NSCLC have been developed by the National Comprehensive Cancer Network (NCCN), the College of American Pathologists/International Association for the Study of Lung Cancer/Association of Molecular Pathology (CAP/IASLC/AMP), and the European Society of Medical Oncology (ESMO) (11,16-18). These guidelines are largely consistent in their recommendations, advising that all patients with advanced NSCLC undergo testing for oncogenic drivers at diagnosis (16-18). They also recommend broad, panel-based testing, which is more efficient than single-gene testing (16-18). The recommended testing methods are next-generation sequencing (NGS) for actionable oncogenic driver alterations from tumor tissue, immunohistochemistry (IHC) for PD-L1, and liquid biopsy for cases where tissue sample is unavailable or insufficient, or for EGFR T790M testing at relapse after first- or second-generation EGFR TKI treatment (16-18). Recommendations for testing focus on the most commonly observed genetic alterations that are targetable with approved drugs, such as EGFR mutations, ALK rearrangements, KRAS (G12C) mutations, ROS-1 fusions, BRAF mutations, RET rearrangements, MET (exon 14 skipping) mutations, MET amplifications, NTRK fusions, and PD-L1 expression (16-18).

Several real-world studies have demonstrated improved clinical outcomes in patients with advanced NSCLC who were managed in accordance with guideline-recommended biomarker testing and molecularly directed first-line therapy (19-21). Conversely, in patients with advanced NSCLC who have actionable mutations, initiating treatment with empiric therapy before obtaining biomarker results has been associated with significantly worse outcomes (22). Despite this, practical barriers continue to hinder the wider implementation of guideline-recommended biomarker testing followed by appropriate targeted therapies, including a lack of awareness or understanding of biomarkers, suboptimal quality or sample management, inappropriate use of testing results, limited patient access, and reimbursement and payment challenges (23-28). Additionally, oncologist-led ordering of biomarker tests, which are often complex and have long turnaround times, can lead to delays in the timely commencement of appropriate therapy, potentially increasing the risk of clinical deterioration and poor patient outcomes (15,22,26,29-31).

Countries in the Asia-Pacific region vary significantly in terms of healthcare infrastructure, access to diagnostics and targeted therapies, and available resources, making the direct application of international guidelines to these settings challenging. For example, according to an IASLC survey on molecular testing in lung cancer, 64% of Asian respondents reported that fewer than 50% of their lung cancer patients undergo biomarker testing (26). As such, expert clinicians from several Asian countries collaborated to develop practical consensus recommendations for NSCLC biomarker testing in Asian patients with advanced NSCLC (32). The healthcare infrastructure and reimbursement framework in Thailand is uniquely structured, encompassing benefits for civil servants under the Comptroller General’s Department (CGD), social security benefits under the Ministry of Labor, and universal coverage under the National Health Security Office (NHSO) of the Ministry of Public Health. Given these diverse reimbursement mechanisms, there exists a critical need for a harmonized biomarker testing guidance tailored to advanced NSCLC. Establishing such guidance would ensure that clinicians across Thailand can provide equitable and standardized biomarker testing to all patients, regardless of their healthcare coverage. In this paper, we aim to explore the current landscape of biomarker assessment and treatment of advanced NSCLC in Thailand and offer recommendations to help ensure that patients receive optimal treatment, improved quality of life, and timely access to suitable healthcare management through Thailand’s existing healthcare schemes.

Methods

Pathologists from high-volume centers providing biomarker testing for lung cancer and handling more than 1,000 cases annually, along with oncologists who are members of the Thai Lung Cancer Group under the Thai Society of Clinical Oncology and practicing in centers managing at least 300 new lung cancer cases per year, were invited to join the expert panel. The panel of experts, comprising one clinical pathologist (Naravat Poungvarin), three anatomic pathologists (A.J., S.S., S.V.), one molecular geneticist (C.T.), and four medical oncologists (L.T., T.R., Naiyarat Prasongsook, V.S.) from academic medical institutions in Thailand, was led by the President of the Royal College of Pathologists, Thailand (S.V.). The panel was required to disclose any conflict of interest related to the development of the recommendations. In March 2023, the panel convened to review recent literature, discuss current clinical practice, and prioritize essential topics for biomarker assessment and management of advanced NSCLC in Thailand. Following the meeting, further discussions on these prioritized topics were conducted via email, and the recommendations were developed and refined. These recommendations are based on available evidence from the literature and the real-world clinical experience of the experts, considering the healthcare infrastructure and practices, insurance and reimbursement settings, and challenges and opportunities in Thailand. Once the experts reached consensus on the recommendations, a draft manuscript outlining the evidence and recommendations was developed and reviewed through multiple rounds of feedback from the panel.

Management of advanced NSCLC with actionable mutations in Thailand

Targeted therapies recommended by the ESMO and NCCN guidelines for the management of advanced NSCLC across various lines of treatment include erlotinib, gefitinib, afatinib, osimertinib, and dacomitinib for EGFR sensitizing mutations; alectinib, crizotinib, ceritinib, brigatinib, and lorlatinib for ALK rearrangements; crizotinib, entrectinib, ceritinib (NCCN), repotrectinib (ESMO), and lorlatinib (NCCN) for ROS-1 fusions; dabrafenib-trametinib, dabrafenib (NCCN) and vemurafenib (NCCN) for BRAF V600E mutation; pralsetinib, selpercatinib, and cabozantinib (NCCN) for RET rearrangements; capmatinib, tepotinib, and crizotinib (NCCN) for MET exon 14 skipping mutations; and sotorasib and adagrasib (ESMO) for KRAS G12C mutation (16-18).

The 2019 Pan-Asian adapted ESMO clinical practice guidelines for the management of patients with advanced NSCLC in Asia recommend targeted therapies for EGFR mutations (erlotinib, gefitinib, afatinib, osimertinib, dacomitinib), ALK rearrangements (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib), ROS-1 fusions (crizotinib, ceritinib), and BRAF V600E mutations (dabrafenib/trametinib), and PD-1 and PD-L1 inhibitors (e.g., pembrolizumab, atezolizumab, nivolumab/ipilimumab) across various lines of treatment for advanced NSCLC (33). Updates to these guidelines are expected in the near future.

The management of advanced NSCLC in Thailand is based on several factors including:

• Pathological diagnosis and results of molecular testing;
• Safety and efficacy of targeted therapies and the treatment duration;
• Reimbursement strategy for molecular tests and targeted therapies;
• Patient access to treatments or clinical trial options.

Access to targeted therapies, categorized as high-cost drugs in Thailand, is influenced by their cost and availability, and is constrained by the coverage profile of existing healthcare insurance schemes—the Civil Servant Medical Benefit Scheme (CSMBS) for government employees and families through the CGD, the Social Security Scheme (SSS) for private sector employees through the Ministry of Labor, and the Universal Coverage Scheme (UCS) for all Thai nationals through the NHSO (12,14,34). Medications listed in the National List of Essential Medicines (NLEM) are reimbursable under all three schemes for the specified indications (12). To be included in the NLEM, drugs undergo Health Technology Assessment, which evaluates cost-effectiveness among other parameters; medications deemed cost-ineffective are typically not included in the list (34). Furthermore, the three healthcare schemes—CSMBS, SSS, and UCS—have differing policies regarding medications that are not included in the NLEM. This variation is particularly noticeable for high-cost specialty drugs, which may be covered under one scheme but not another (34). For example, the CGD has approved reimbursement for ceritinib and more recently brigatinib as first-line treatments for ALK-rearrangement positive advanced NSCLC under the CSMBS. However, neither the SSS nor UCS offer the same coverage, creating disparities in patient access to these treatments. The reimbursement policies are driven by the cost of the medication which is the major cost of healthcare in Thailand. As a result, patients’ access to certain treatments depends on their insurance coverage, contributing to inconsistencies in healthcare availability and influencing treatment options across Thailand. While some high-cost drugs are covered by these programs, many targeted therapies are financed through patient self-payment and private insurance, particularly in Bangkok and large urban areas. Access to medical care in rural areas is significantly limited compared to urban centers. The Ministry of Public Health oversees the national health policy and operates most government health facilities, while the NHSO allocates funding through UCS (12,35).

Mutations in EGFR are among the most common driver mutations in NSCLC (36); EGFR mutations are seen in 54–68% of Thai patients with NSCLC and are also the most common targetable mutation in NSCLC in Thailand (37-40). ALK rearrangements are seen in 2–5% of all NSCLC patients in both Caucasian and Asian populations (41); studies have reported a prevalence range 3.2–15% in Thailand (40,42-44). ROS-1 fusion has been reported in approximately 0.9–2.6% of patients with NSCLC worldwide and 1.9–2.4% of Thai patients (38,40,45). Co-mutations have also been reported in 24.1% of Thai patients with lung cancer (38).

Currently, driver mutation testing for advanced NSCLC in Thailand is primarily available for EGFR mutations and ALK rearrangements, and for ROS-1 fusions in some hospitals. Testing for other targetable gene alterations such as BRAF V600E, NTRK, RET, and MET exon 14 are limited due to the reimbursement restrictions. Figure 1 illustrates the current pathway for the management of advanced NSCLC with actionable alterations in Thailand.

• Testing for EGFR mutations is covered under all three insurance schemes (46), and quantitative polymerase chain reaction (qPCR) is the most commonly used method for testing in Thailand. Targeted agents available for EGFR mutation-positive advanced NSCLC in Thailand include erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib. However, only first-line erlotinib is covered for reimbursement under all healthcare schemes for sensitizing EGFR mutation-positive advanced NSCLC (Figure 1) (12). Although gefitinib is not covered under any of the schemes for first-line therapy, reimbursement can be requested by CSMBS-insured patients under the Oncology Prior Authorization Program (OCPA) if side effects from first-line erlotinib are intolerable (12). Upon disease progression, EGFR T790M testing from either tissue or liquid biopsy is recommended to determine the next steps (47). Osimertinib, the treatment of choice in EGFR T790M-positive advanced NSCLC (14), is only reimbursable for CSMBS-insured patients in the second line (Figure 1) (12).
• For patients with ALK-rearrangement positive NSCLC, crizotinib, ceritinib, brigatinib, alectinib, and lorlatinib are available for use in Thailand, but only first-line ceritinib and brigatinib are reimbursable for CSMBS-insured patients under OCPA (Figure 1); other ALK inhibitors do not meet the reimbursement criteria for first-line therapy under any scheme. IHC is used to detect ALK rearrangements in Thailand, and this is covered by the CSMBS scheme (48).
• For ROS-1-positive advanced NSCLC confirmed by fluorescence in situ hybridization (FISH)/reverse transcription-polymerase chain reaction (RT-PCR)/NGS, crizotinib and entrectinib are the treatments of choice (16,18), and these are also available in Thailand; however, only first-line crizotinib is covered under CSMBS (Figure 1).
• Tumor PD-L1 testing is commonly done and easily accessible in Thailand. Several immunotherapies are available for advanced NSCLC patients in Thailand, including pembrolizumab, atezolizumab, nivolumab, ipilimumab, durvalumab, and tremelimumab. Nevertheless, only first-line pembrolizumab is covered for reimbursement under CSMBS for advanced NSCLC with high PD-L1 expression (PD-L1 tumor proportion score ≥50%).

Figure 1 Pathway for the management of advanced NSCLC with actionable driver mutations and PD-L1 expression in Thailand. *, pemetrexed is reimbursed by CSMBS only. 1L, first-line; CSMBS, Civil Servant Medical Benefit Scheme; NSCLC, non-small cell lung cancer.

As such, restrictions on targeted therapy reimbursement are a major factor influencing oncologists’ decisions regarding molecular testing and treatment planning in Thailand (Figure 1).

In public hospital settings in Thailand, oncologists usually adopt an exclusionary molecular testing approach, whereby the most common actionable mutation is tested first with sequential testing for other mutations conducted only if the initial test results are negative. A single-gene qPCR testing for EGFR mutation, and IHC for ALK and ROS-1 fusions (confirmed by FISH/RT-PCR/NGS upon positive IHC results) are commonly performed. In fact, single-gene testing strategy can be inefficient and time-consuming, especially considering the growing number of actionable targets. A cost-effectiveness study in the United States evaluated the economic impact of NGS vs. single-gene testing to detect genomic alterations in advanced NSCLC and found that upfront NGS was associated with cost savings as well as a shorter time to test results (49). In Thailand, however, financial considerations are a major barrier to the utilization of multiplex testing methods such as NGS which require patients to self-pay for the tests. Furthermore, NGS is associated with a long turnaround time—in Thailand, time-to-receive results is 1–10 days for qPCR vs. 10–30 days for NGS (40). An exclusionary testing strategy, with testing for EGFR mutations and ALK IHC first, followed by NGS in patients with advanced NSCLC in Hong Kong, was found to be associated with the shortest time to test results and most cost saving, and this testing methodology could potentially be considered for Thailand (50).

Recommendations for molecular evaluation of advanced NSCLC in Thailand

Our recommendations for molecular testing for advanced NSCLC are organized into three main topics based on the discussions at the meeting.

Multidisciplinary team (MDT) management and patient communication

Increased understanding of oncogenic drivers in NSCLC and availability of targeted and immunotherapeutic agents have led to remarkable changes in advanced NSCLC treatment (16-18). Hence, it is important to test newly diagnosed patients with advanced NSCLC for targetable alterations before treatment initiation. An MDT approach, with oncologists, thoracic surgeons, radiologists, pathologists, and other ancillary staff working in close collaboration, has been shown to be associated with longer overall survival and better quality of life for patients, improved utilization of all treatment modalities, and adherence to guidelines (51-53).

Establishment of pathways and workflows to guide the MDT, such as a standing order for reflex testing or protocols for sample management, will ensure a smooth patient journey. The pathways of care should outline the role and responsibilities of all staff involved in the MDT (oncologists, thoracic surgeons, pathologists, technicians, etc.) and ensure continuous education and training of all members on molecular tests, targeted therapies, and relevant guidelines. The pathways should be evaluated periodically in view of the continuously evolving field of molecular diagnostics and precision medicine.

Additionally, patient satisfaction was improved with multidisciplinary care compared to a conventional serial care approach (52). Patient involvement in the decision-making process is one of the central pillars of patient-centered care. In a complex reimbursement scenario such as in Thailand, it is crucial for clinicians to elaborate the cost for biomarker testing and target therapy and the possible reimbursement mechanism available to patients, prior to selection of therapy.

While a fully integrated MDT for managing advanced NSCLC is not available in all healthcare facilities in Thailand, most university hospitals and public cancer hospitals under the Ministry of Public Health have well-established MDT frameworks in place. We recognize that implementing an MDT approach can be challenging for smaller hospitals and those in rural settings. To overcome these limitations, hospitals can explore strategies such as collaborations with tertiary care centers, creation of referral networks to ensure patients receive specialized care, and establishment of virtual MDT teams to provide consultative support. Additionally, cross-hospital partnerships, regular interdisciplinary training programs, and standardized treatment protocols can help enhance coordinated care, ensuring that patients in resource-limited settings receive optimal management.

• Early implementation of MDT for the management of patients with NSCLC is recommended to ensure adequate and appropriate diagnostic procedures, molecular tests, and personalized care, and to achieve the overarching goal of improving treatment efficiency and patient care.
• Before selecting therapy, clinicians should elaborate to the patients the cost and accessibility of biomarker testing and the targeted therapy, and the possible reimbursement mechanisms available, and should involve patients in the decision-making process.
• All stakeholders involved in the management of patients with advanced NSCLC should be educated consistently on the most recent updates in biomarkers, targeted therapies and guidelines for NSCLC.

Biomarker testing for advanced NSCLC in Thailand

To select biomarkers to test before initial therapy for patients with advanced NSCLC, it is important to consider the known prevalence of actionable genetic alterations in the population, the availability of targeted therapies, patient access to testing, and the reimbursement coverage of the biomarker tests and treatments. Since EGFR mutations and ALK rearrangements are the most prevalent actionable mutations with available and reimbursable targeted therapies in Thailand, exclusionary testing with EGFR mutations and ALK IHC tested upfront is our recommended approach in Thai settings (Figure 2, Table 1) (16-18,32). Also, all patients should be simultaneously tested for PD-L1 expression at the first screening (Figure 2). Pharmaco-economic analyses factoring in the costs of various testing techniques and strategies in Thailand are warranted to get further clarity on costs and time to test results. We acknowledge that exclusionary testing has limitations, as it may fail to detect all genomic alterations, potentially delaying or missing less common but clinically significant and treatable mutations inherent to the sequential testing approach. However, given current constraints in access to broad panel testing, exclusionary testing remains a viable interim strategy to facilitate timely targeted treatment for patients with advanced NSCLC until broader testing becomes more readily available.

Figure 2 Recommended exclusionary molecular biomarker testing for advanced NSCLC recommended in Thailand. *, dependent of patient access. EGFR TKI, epidermal growth factor receptor tyrosine kinase inhibitor; IHC, immunohistochemistry; NSCLC, non-small cell lung cancer.

Furthermore, when NSCLC patients with negative EGFR mutation by qPCR were subsequently tested by NGS (Chulalongkorn GenePro Center) in Thailand, targetable mutations were found in 49/104 (47%) patients; eight of those with newly discovered EGFR mutations not detectable by qPCR (unpublished data). In another study from Siriraj Hospital, among EGFR negative cases by PCR, NGS detected uncommon EGFR mutations (L861R/L833F, A750FS, G779F) in three cases (40). Similarly, a recent study from South Korea demonstrated the efficacy of NGS in detecting missed EGFR mutations (54). Therefore, we recommend a limited multigene panel test to follow negative tests for EGFR mutation and ALK rearrangement (Figure 2, Table 1). After excluding EGFR mutation, a limited NGS panel is the most appropriate next step. Although NGS currently has a long turnaround time in Thailand due to limited access and affordability, reimbursement could help address this by increasing sample volume at designated testing centers, ultimately reducing the cost per test.

Reflex testing for EGFR mutations and ALK rearrangements has been shown to improve the time to optimal systemic therapy and the quality of biomarker testing for patients with advanced NSCLC (54). With an established reflex testing protocol in place, the possibility of testing being missed in a particular patient is reduced (55,56). The CAP/IASLC/AMP guidelines suggest that pathologist initiated reflex testing in lung cancer is reasonable; however, real-world challenges could impact the adoption, such as concerns over high costs (tests ordered by pathologists with incomplete access to patient information could be deemed unnecessary or inappropriate), reimbursement practices which vary by country, limited tissue access, and the failure to achieve consensus among various stakeholders (29,31). Although we do not recommend the adoption of a reflex testing approach for NSCLC in Thailand at this time, it could potentially be considered in the future. Initiation of reflex testing will need deliberations between various institutional stakeholders including pathologists, oncologists, radiologists, thoracic surgeons, policymakers, and administrators, with due consideration of the costs and local guidelines, and clearly defined roles and responsibilities (17,56).

The laboratory quality assessment, evaluated by the Thailand National External Quality Assessment Scheme for Precision Molecular Pathology in 2022, assessed 22 member laboratories from both government and private settings in Thailand (57). Two-thirds of the member laboratories were certified from at least one of the laboratory quality standards. It was observed that almost all (94%) qPCR methods to detect EGFR mutation in the member laboratories were approved either by the United States Food and Drug Administration or an equivalent certifying organization; the methods used to detect gene fusion, however, were not certified (unpublished data). We strongly recommend that all laboratories in Thailand conducting molecular testing for NSCLC should participate in external quality assurance and encourage all laboratories get appropriate accreditation.

Our recommendations for biomarker testing for advanced NSCLC in Thailand compared to the other published guidelines are illustrated in Table 1.

Biomarker testing in resource-limited settings, particularly in smaller hospitals and rural areas in Thailand, may present challenges. To enhance access in these settings, strategic measures can be explored, such as improving sample collection capabilities in remote areas for initial evaluation and establishment of a logistic infrastructure for sample shipment from rural hospitals to central laboratories; and real-time virtual consultations between rural clinicians and specialists in urban tertiary centers using digital pathology platforms; and collaboration between universities, pharmaceutical companies, and non-governmental organizations to expand diagnostic infrastructure and training.

• Biomarker testing decisions should be made with due consideration of patient accessibility to treatment and tissue availability.
• Exclusionary testing for EGFR mutation and ALK rearrangement, along with PD-L1 expression, followed by a limited multigene panel test (EGFR, KRAS G12C, ROS-1, BRAF, RET, NTRK, MET exon 14, HER2) if EGFR mutation and ALK rearrangement testing is negative, is the optimal technique/sequence for NSCLC biomarker testing in Thailand (Figure 2).
• All laboratories in Thailand conducting molecular testing for NSCLC should participate in external quality assurance, and all laboratories should get appropriate accreditation.

Engagement and collaboration between clinicians and healthcare policymakers

Our recommendations for the molecular testing of advanced NSCLC are based on the essentialism of coverage and reimbursement for biomarker testing for patients with NSCLC in Thailand. We believe that the priority is to encourage government agencies to raise the optimal reimbursement standard for therapies to ensure that all patients with NSCLC receive appropriate treatment based on their biomarker testing results. Currently, patients have varying access to targeted therapies, primarily depending on different healthcare schemes. The second priority is to then move towards raising the reimbursement standard on biomarker testing. Once targeted therapies become available and accessible for reimbursement, the case for reimbursement of associated biomarker testing will become stronger.

We have recommended limited multigene panel testing in patients with advanced NSCLC who test negative for EGFR mutations and ALK rearrangements. This test should include EGFR, ROS-1, BRAF, KRAS, MET, HER2, RET, and NTRK. The short-term plan of the expert panel is to work cross-functionally with the public and private sector to develop the testing support programs for patients under the CSMBS scheme. Subsequently, over the long term, we aim to work in collaboration with the CGD who is responsible for CSMBS beneficiaries, to embed limited multigene panel testing for patients under CSMBS whose EGFR results are negative. The optimal goal is to strengthen the network between the NHSO and Social Security Office (SSO), both of which cover lung cancer, to ensure that EGFR mutation-positive patients who are missed under UCS will have the right to access proper biomarker testing. Continuous engagement and collaboration between various healthcare policy makers as well as academicians/clinicians is essential for the development and establishment of reimbursement schemes for novel targeted therapies to ensure that all patients with advanced NSCLC receive appropriate treatment promptly. An example of successful collaboration was the retrospective analysis by Khiewngam et al. which provided real-world evidence for the benefit of EGFR TKI therapy for EGFR mutation-positive NSCLC patients in line with the reimbursement of EGFR TKIs in patients under UCS and SSS (12). Furthermore, a cost-effectiveness analysis of first-line EGFR TKI for advanced NSCLC in Thailand contributed valuable evidence to support the decision to include erlotinib in the Thai NLEM as first-line treatment for patients with EGFR mutation-positive advanced NSCLC, broadening erlotinib access on healthcare schemes in Thailand, thereby demonstrating the value of local real-world outcome data for healthcare policy decision-making (12,58). While engagement of clinicians with government agencies plays a pivotal role in shaping policy, additional strategies can further influence reimbursement decisions, including:

• Developing medical society-driven and evidence-based clinical practice guidelines and consensus recommendations;
• Generating cost-utility analysis for informing clinicians and policymakers on the implications of resource allocation and for supporting drug cost negotiations for inclusion of therapeutic agents in the NLEM;
• Generating high-quality data on the local impact of novel treatments to support national healthcare policymakers in the timely evaluation and decision on clinically impactful treatments nationwide;
• Encouraging patient groups and healthcare organizations to advocate for expanded biomarker testing and targeted therapy coverage.

Research into patient access to anti-cancer medicines under public health insurance schemes in Thailand by Patikorn et al. in 2019 concluded that although there was inequity in access to anti-cancer medicines, the overall coverage and patient access to these medicines across the three healthcare schemes were sufficient (35). However, the landscape of lung cancer treatment continues to evolve rapidly. By integrating these approaches, we can support drug cost negotiations and promote harmonized biomarker testing guidelines, ensuring equitable treatment access for all patients with advanced NSCLC in Thailand.

• To ensure that all patients with advanced NSCLC receive appropriate treatment based on their biomarker testing results, clinicians should work collaboratively with policymakers to encourage them to raise the optimal reimbursement standard for therapies and molecular tests.
• It is imperative to generate high-quality data on the local impact of novel treatments to support national healthcare policymakers in the timely evaluation and decision on clinically impactful treatments nationwide.
• Given the paucity of data on the gaps and challenges in biomarker testing and targeted treatment uptake in Thailand, further research and gap analysis, particularly real-world studies and cost-utility analysis, are warranted.

Barriers to adoption of biomarker testing in NSCLC in Thailand

Based on the current clinical practices and our experience in Thailand we have identified key barriers to the adoption of biomarker testing which should be urgently addressed.

• Limited reimbursement of molecularly targeted therapies.
• Limited availability of public funding to support biomarker testing, as well as restricted reimbursement regulations for biomarker testing in various healthcare schemes.
• Diverse laboratory infrastructure, referral pathways, and inconsistent laboratory accreditation.
• Inadequate physician and patient awareness of available biomarker tests and their impact on the utilization of precision medicine.

Conclusions

Increased understanding of molecular profiles in NSCLC has led to the development and application of targeted treatment for patients harboring actionable genetic alterations. Multiple molecular testing approaches are available to guide the treatment strategy for NSCLC patients. In this milieu, we have provided recommendations for molecular testing for advanced NSCLC patients in Thailand. Our recommendations encompass an exclusionary strategy for molecular testing, the value of MDT in the management of patients with advanced NSCLC, and the importance of laboratory accreditation and external quality assurance programs, and also highlight the need for high-quality data on the local impact of novel treatments to support policymakers in making these treatments available to the appropriate patients. These recommendations have been reviewed by the Thai Lung Cancer Group and the Royal College of Pathologists of Thailand.

Acknowledgments

The authors would like to thank In Vivo Communications Asia Pte. Ltd. for editorial assistance which was funded by Amgen Thailand.

Footnote

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-201/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-201/coif). All authors acknowledge In Vivo Communications Asia Pte. Ltd. for editorial assistance which was funded by Amgen Thailand. S.S. reports that he has received honorarium for lectures from Amgen, AstraZeneca, MSD, Novartis, and Takeda; support from the Health Systems Research Institute of Thailand for genetic testing for non-small cell lung cancer in Thai patients; and is the secretary of International Academy of Pathology (IAP)-Thailand Division. Naiyarat Prasongsook reports that he has received speaker honoraria from Amgen, AstraZeneca, BMS, Roche, MSD, Takeda; travel support from AstraZeneca, Roche, MSD. L.T. reports that he has received honoraria from Amgen, Roche, AstraZeneca, MSD, BMS, Johnson & Johnson, Novartis, Eisai, Pfizer, Takeda; travel support from Amgen, MSD, Roche, AstraZeneca. T.R. reports that she has received honoraria from AstraZeneca, Roche, BMS, J&J, Pfizer, Amgen, Takeda, MSD; has participated in data safety monitoring board/advisory board for AstraZeneca, Roche, BMS, J&J, Pfizer, Amgen, Takeda, Yuhan, MSD; and has received grant for Clinical Research from AstraZeneca, Roche, MSD, Yuhan (paid to her institution). Naravat Poungvarin reports that he has received speaker honoraria from Biogenic, AstraZeneca, Pfizer, Amgen, and Roche. V.S. reports that he has received consulting fees from Astellas, AstraZeneca, Merck Sharp & Dohme, Roche, Novartis, Takeda; speaker honoraria from Astellas, AstraZeneca, Merck Sharp & Dohme, Roche, Novartis, Takeda, Pfizer, Eisai; travel support from Eisai, Roche, AstraZeneca, MSD, Celltrion; research support from Astellas, AstraZeneca, Daiichi-Sankyo, Merck Sharp & Dohme, Novartis, Roche, Takeda. The authors have no other conflicts of interest to declare.

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