Combination therapy faces reimbursement challenges for cancer patients in South Korea

The method of increasing the effectiveness of treatment by using two or more anticancer drugs together, known as "combination therapy," has established itself as a trend in cancer treatment; however, it has been pointed out that the institutional barriers are high for patients receiving treatment in the country.

This is due to the time it takes for drugs to be covered under insurance and the principle that if existing reimbursed drugs and new anticancer drugs are used together, both drugs will be classified as "non-reimbursed" and the patient will bear the full cost.

Lee Ju-young, a member of the Reform Party from the Health and Welfare Committee of the National Assembly, held a policy discussion on "Improving access for cancer patients to combination therapy" in Seminar Room No. 3 of the National Assembly Member’s Office at 2 p.m. on the 17th.

Physicians participating in the discussion pointed out the need to improve the reimbursement criteria for combination therapy in line with the trend of anticancer treatment.

The current system applies the "combination therapy" that uses anticancer drug A, which is reimbursed, along with anticancer new drug B that is not yet reimbursed, treating the already reimbursed drug as "non-reimbursed," and there is a need to change this standard.

According to Professor Kim In-ho of Seoul St. Mary's Hospital, drug A, which costs 2 million won for a month of treatment, is covered by health insurance and the patient's out-of-pocket cost is 5%, allowing the patient to receive treatment for 100,000 won; however, if trying to maximize the treatment effect by applying combination therapy with drug B costing 2 million won, drug A would also be treated as non-reimbursed, resulting in the patient having to bear 4 million won entirely.

Professor Kim cited metastatic bladder cancer as an example. The life expectancy over the past 50 years has been about 1 year or less, and recent immune therapy clinical trials have not surpassed the existing platinum therapy (chemotherapy), but combining antibody-drug conjugate (ADC) targeted therapy and immune therapy has shown results that extend the survival period of existing chemotherapy by more than 2 times.

He noted, "Although it has been proven through clinical research and various data that combination therapy can significantly improve survival rates and enhance anticancer treatment effects, the reimbursement ratio in the country is remarkably low, and the time it takes to get reimbursed is long, increasing the physical and economic burdens on patients with metastatic cancer." ADC is the latest targeted therapy drug known as a guided missile anticancer agent that delivers drugs specifically to cancer cells.

Professor Kim stated, "A flexible reimbursement review standard for combination therapy should be quickly established to improve access to new drugs for cancer patients," adding, "As a clinician treating cancer patients, we need to consider whether it is reasonable for this gap to exist. " According to data analyzed by Lee Ju-young's office through the Ministry of Food and Drug Safety, it takes an average of 46 months (4 years) for new drugs approved by the U.S. Food and Drug Administration (FDA) to gain approval in the country.

Ra Sun-young, president of the Korean Cancer Society, said, "More than 70% of the anticancer drugs currently in development are combination therapies, and as new drugs are developed, the limits of cancer treatment are being overcome, but the domestic system cannot sufficiently keep up with this anticancer drug development environment and trend; no matter how good a drug is, if it is not reimbursed, it is nothing more than a pie in the sky for doctors, patients, and caregivers."

The paradigm of anticancer therapy has continued to evolve. Anticancer drugs are broadly classified into generations 1 to 3; the first generation consists of chemically synthesized drugs. Chemical anticancer drugs flow through the bloodstream, destroying not only cancer cells but also healthy cells, causing severe side effects such as liver toxicity. Second-generation anticancer drugs are targeted therapies that attack only cancer cells using antibodies, and the third generation consists of the current mainstream immune anticancer drugs. Immune anticancer drugs do not directly target cancer cells but induce the body's immune cells to attack cancer cells.

As various new drugs emerge, the methods of combination therapy have also diversified. Examples include "antibody-drug conjugate (ADC) + immune anticancer drug," "immune anticancer drug (PD-1, PDL1 inhibitors) + immune anticancer drug (CTLA4 inhibitors)," "immune anticancer drug + targeted anticancer drug," and "immune anticancer drug or targeted anticancer drug + chemotherapy." From 2007 to 2021, clinical studies of anticancer drugs approved by the U.S. Food and Drug Administration (FDA) showed that the percentage of monotherapy decreased from 70% in 2007 to 20% in 2021, while combination therapy increased to 80%. This indicates that combination therapy has become the mainstream in cancer treatment.

Patient organizations have also called for the improvement of reimbursement criteria for anticancer drug combination therapy to match the pace of drug development.

Lee Eun-young, a representative of the Korea Patient Groups Alliance, pointed out, "It is unreasonable that when a reimbursed drug meets a non-reimbursed new drug, the entire treatment is excluded from health insurance coverage and converted to non-reimbursed," adding, "I have raised this issue since 2017, and while health authorities have reviewed and discussed it, there has been no actual improvement."

Ultimately, it comes down to money. Seo Dong-cheol, an honorary professor at Chung-Ang University College of Pharmacy, explained, "In the case of combination therapy, it is more common to have drugs from different companies, which poses limitations as different corporations have different interests in setting prices." He added, "Moreover, price setting and negotiations could be regarded as collusion under fair trade laws, preventing pharmaceutical companies from sharing information or engaging in price discussions."

A representative from the health authorities present that day also agreed on the need to improve reimbursement criteria for combination therapy. However, they explained the limitation that the government, which must manage health insurance finances, cannot simply open its coffers.

Park Hee-yeon, an official from the Health Insurance Policy Division of the Ministry of Health and Welfare, said, "The issue of reimbursement for combination therapy is intertwined with the pricing system and the issues of treatment sequence and drug assessment, making improvement difficult." He stated, "The Ministry also has the will to improve this issue," and added, "We are reviewing system improvements and discussing them with the Health Insurance Review and Assessment Service responsible for practical implementation."

Kim Gook-hee, director of the Drug Management Division of the Health Insurance Review and Assessment Service, said, "We are concerned about whether health insurance finances can handle the increasing number of combination therapies and more expensive anticancer drugs in the future, and whether all combination therapies should be covered," adding, "The Cancer Disease Review Committee evaluates and assesses the reimbursement of treatments by comprehensively considering treatment sequences, survival periods, and side effects."

Director Kim stated, "As of 2023, the increase rate of anticancer drug costs reached 26%," noting, "There will be more combination therapies and more expensive anticancer drugs coming out, raising concerns about whether health insurance finances will remain sustainable if they are reimbursed," and added, "There needs to be a separate system in place regarding new anticancer drugs."