Biliary tract cancer is known to have the highest mortality and incidence rates in Korea in the world. It is also one of the most difficult cancers to treat in Korea due to the limited options, or ‘weapons’ available to doctors in practice.

However, immuno-oncology drugs are being approved for the first-line treatment of biliary tract cancer and are emerging as an alternative in the field.

As a result, the issue of ‘reimbursement’, which remains the biggest obstacle to the utilization of such treatment, is emerging as an issue. Attention is focused on whether Imfinzi, which the company planning to reapply for reimbursement this year, will be able to overcome this hurdle.

According to industry sources on the 2nd, AstraZeneca recently filed an application with the Health Insurance Review and Assessment Service’s Cancer Disease Deliberation Committee to review the reimbursement of the Imfinzi (durvalumab)-GemCis combination as a first-line treatment for biliary tract cancer.

Imfinzi was approved for the first-line treatment of biliary tract cancer in Korea last year and is currently being used without reimbursement in practice. Ever since the indication was approved, AstraZeneca has been applying for reimbursement, but only the GemCis therapy part has been granted reimbursement.

This is because the government has set Imfinzi’s use as ‘non-reimbursed’ because reimbursing the entire Imfinzi-GemCis combination as a first-line treatment of biliary tract cancer would require significant additional health insurance funding.

Amid such background, MSD's Keytruda (pembrolizumab) also entered the biliary tract cancer market, securing domestic marketing authorization and entering competition in the field.

Among these, the European Society for Medical Oncology (ESMO) recently released guidelines that highly evaluated Imfinzi’s adequacy for reimbursement. This is the first global recognition of the need for Imfinzi’s reimbursement in the face of the CDDC review.

Specifically, ESMO published The Pan-Asian Guidelines Adaptation (PAGA) for patients with biliary tract cancer in August. This is the first Asian biliary tract cancer guideline created by ESMO, given that the disease is rare in the West but has a high prevalence in Asia.

One notable part is the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scale.

The ESMO-MCBS indicates the value of a new treatment option based on clinical data on a scale of 1 to 5 and can be used as a reference point for reimbursement discussions. On the guideline's scale, higher scores of 4 or 5 indicate a higher clinical benefit that warrants reimbursement.

For example, in September last year, the immuno-oncology drug Opdivo, which was approved for reimbursement in the first-line treatment of Stage IV gastric cancer, received an ESMO-MCBS Grade 4. A Grade 4 drug is considered to have sufficient clinical benefit to warrant rapid reimbursement, the same as a Grade 5 drug.

Accordingly, the latest ESMO-MCBS of immuno-oncology agents as a first-line treatment for biliary tract cancer rated Imfinzi as Grade 4 and Keytruda as Grade 1. Unlike in the first line, Keytruda received a higher grade of 3 as a second-line treatment of patients with MSI-H or dMMR biliary tract cancer.

The difference in the grades was driven by the results of the 2 drugs' Phase III trials. Both immuno-oncology agents demonstrated significant improvements in OS in their respective Phase III studies, TOPAZ-1 and KEYNOTE-966, but only Imfinzi demonstrated significant improvements in PFS,

In particular, Imfinzi demonstrated a greater OS benefit in Asian patients in the TOPAZ-1 regional sub-analysis.

Upon the announcement, the clinical community has been eagerly awaiting to see if Imfinzi will be presented at HIRA’s upcoming CDDC meeting.

‘While various treatment options for gastric and lung cancers are available with reimbursement for each stage, treatments for biliary tract cancer remained non-reibmbursed for more than a decade, except for GemCis as a first-line treatment," said Myung-Ah Lee, Professor of Medical Oncology at Seoul St. Mary's Hospital. "We should consider how Imfinzi has demonstrated that it can extend the 1-year life expectancy of biliary tract cancer patients to 3 years."