Calls for reform in NHI access for third-line mCRC treatment

Restricted reimbursement option after first-line and second-line treatments…limited patient options

Calls for the need for insurance coverage considering survival extension and quality of life

There is a growing demand in South Korea to improve access to third-line treatments under the National Health Insurance (NHI) for metastatic colorectal cancer (mCRC) to enhance patient survival.

​While health insurance coverage is relatively comprehensive for first- and second-line treatments in South Korea, global standard-of-care agents used in subsequent lines remain non-reimbursed. In response, health authorities have acknowledged the high unmet medical need in third-line treatment, stating that they are evaluating measures to improve patient access.

On the 24th, a symposium titled "Policy Forum for Improving the Treatment Environment for Metastatic Colorectal Cancer Where Early Treatment Access Determines Survival" was held at the National Assembly, hosted by Representative Mihwa Seo of the Democratic Party of Korea.

Rep. Seo stated, "In metastatic colorectal cancer, treatment timing and therapeutic access exert a direct impact on overall survival, yet reimbursed options in third-line are not available in South Korea," and added, "A rational reimbursement framework must be established to prevent patients from forfeiting treatment due to financial toxicity."

​A policy symposium on improving the treatment environment for metastatic colorectal cancer was held on July 24 at the National Assembly Members' Office Building.

Third-line treatments are not reimbursed...Leading to drops in treatment rates

​Presenting at the forum, Professor Myung Ah Lee of the Division of Oncology at Seoul St. Mary's Hospital diagnosed that as patients with metastatic colorectal cancer progress through sequential lines of therapy, acquired resistance and disease progression progressively deteriorate their systemic performance status. Dr. Lee explained that non-reimbursed drug costs starting at the third-line setting lead to a sharp decline in the proportion of patients maintaining ongoing treatment.

​Professor Lee pointed out, "Reimbursement is well-integrated through first- and second-line systemic chemotherapy, resulting in a manageable financial burden for patients. However, from the third-line setting onward, patients with good performance status are frequently unable to receive treatment simply because no reimbursed agents exist," and added, "An increasing number of patients are discontinuing treatment despite viable therapeutic opportunities due strictly to financial constraints."

​Currently, first-line therapy for metastatic colorectal cancer primarily utilizes oxaliplatin- or irinotecan-based cytotoxic chemotherapy in combination with targeted biologics. Second-line treatment involves switching to the alternative chemotherapy backbone not administered in the first-line setting.

​However, the treatment landscape shifts dramatically following failure of both lines. While a small subset of patients with specific biomarkers can access immune checkpoint inhibitors or targeted agents, the eligible patient population remains narrow.

​For the majority of patients, global standard-of-care regimens recommended in guidelines, such as the combination of 'Lonsurf (trifluridine/tipiracil)' plus 'Avastin (bevacizumab)', 'Stivarga (regorafenib)', and 'Fruzaqla (fruquintinib)', are all non-reimbursed in South Korea.

​Professor Lee emphasized, "In the U.S. and Europe, Stivarga, Lonsurf-Avastin combination, and Fruzaqla are recommended from the third-line setting, but none of these regimens are reimbursed in South Korea," and added, "We need a regulatory environment where therapeutics capable of preserving quality of life alongside overall survival can enter the national health insurance benefit umbrella more rapidly."

​Access to Next-Generation Sequencing (NGS) testing for precision oncology was also pointed out to be resolved, as the absence of genomic profiling data restricts patient eligibility for biomarker-driven novel drugs and clinical trial enrollment.

​Professor Lee stated, "While international practice is moving toward routine genomic profiling for patients with metastatic or recurrent solid tumors, domestic reimbursement in Korea remains restricted outside of specific cancer types," and expressed concerns that "Consequently, patients who wish to participate in clinical trials for novel therapies often cannot enroll due to a lack of genetic sequencing results."

​Experts urged that even in third-line and subsequent settings, clinicians must have the therapeutic flexibility to decide the sequence of care based on patient performance status, prior treatment history, and specific toxicity profiles.

​Professor Dong-Hoe Koo of the Division of Hematology-Oncology at Kangbuk Samsung Hospital explained, "Each therapeutic option possesses distinct efficacy as well as unique toxicity profiles, such as fatigue, thrombocytopenia, hand-foot syndrome, and hypertension,” and added, “Drug selection should be personalized according to prior treatment exposure and individual patient vulnerability to specific adverse events."

Dr. Koo added, "Because third-line therapeutics established as global standards remain non-reimbursed in Korea, a patient's financial status directly dictates therapeutic choices," and added, "Reimbursement access must be improved so that patients with preserved performance status can gain survival opportunities through third-line and subsequent therapies."

(From left) Min-Jung Kim, Administrative officer at the Ministry of Health and Welfare; So-Young Lee, Manager of the Pharmaceutical Benefit Management Division at HIRA; Professor Dong-Hoe Koo of Kangbuk Samsung Hospital; and Professor Myung Ah Lee of Seoul St. Mary's Hospital.

Discussions continue on regulatory reforms to address unmet medical need

​During the panel discussion, structural limitations in the pharmacoeconomic evaluation process and directions for regulatory reform emerged as key agenda items.

​Reporter Yun-Ho Eo of DailyPharm pointed out that novel therapeutics approved via placebo-controlled clinical trials face structural disadvantages during pharmacoeconomic evaluations, as they are forced to compete against outdated comparator drugs.

​Eo stated, "Recently, we have observed significant delays between passing the Cancer Disease Review Committee (CDRC) and being tabled before the Pharmaceutical Reimbursement Evaluation Committee (PREC)," and added, "Special policy mechanisms need to be considered for diseases where a new treatment landscape has formed, but cost-effectiveness is inherently difficult to prove due to outdated comparator drugs."

Eo added, "Even if a drug does not qualify for a full pharmacoeconomic evaluation waiver or an elevated Incremental Cost-Effectiveness Ratio (ICER) threshold, we need flexible regulatory pathways for drugs occupying an intermediate tier," and added, "Multinational pharmaceutical subsidiaries in Korea must also actively negotiate with their global headquarters rather than abandoning reimbursement due to challenging external environments."

Government representatives acknowledged the severity of the coverage gap in third-line metastatic colorectal cancer. They explained that regulatory reforms are underway to incorporate high unmet medical needs into reimbursement decision-making.

Lee stated, "We are aware of the reality that patients face due to a lack of options in third-line therapy, and we feel a deep sense of responsibility," and added, "Under the principle that unmet medical needs in life-threatening severe diseases should be evaluated through dedicated mechanisms, we are accelerating regulatory reforms."

​The government currently operates a "conditional early listing with post-evaluation" pathway for high-cost novel drugs that demonstrate substantial unmet medical need despite limited clinical evidence. Separately, health authorities are evaluating flexible ICER thresholds for therapies indicated for severe diseases where applying standard ICER benchmarks is unfeasible.

Lee stated, "A research initiative evaluating the application of flexible ICER thresholds is scheduled for completion around November of this year, after which implementation will proceed," and added, "Even before the completion of this research, working-level staff is thoroughly reviewing data so that the evaluation committee can adequately consider disease characteristics and unmet needs."

Lee noted, "In reviewing third-line treatments, including Fruzaqla, we are re-examining the reasons why previous agents failed to secure reimbursement, the criteria applied at the time, and our newly evolved administrative procedures," and added, "Even before the research findings are published, we will fully consider the third-line colorectal cancer reimbursement gap within the committee's existing criteria and authority."

Min-Jung Kim, Manager of the Division of Health Insurance Benefits at the Ministry of Health and Welfare, noted, "Because National Health Insurance operates within a finite budget, we must strike a balance between patient access and fiscal sustainability," and added, "We are striving to establish rational reimbursement solutions by comprehensively reviewing the clinical value of therapeutics and their impact on patient quality of life."

Kim added, "It is important for pharmaceutical companies to demonstrate proactive negotiation and a willingness to improve patient access," and concluded, "The government will continue driving regulatory improvements to ensure that essential therapeutics are supplied to patients more rapidly."