[Desk’s View] Unmet needs remain in immuno-oncology

Immuno-oncology has now become quite a fairly common term. It is a term even ordinary people are likely to have heard at least once. More than a decade has already passed since the term was first introduced to Korea. At present, immuno-oncology drugs have expanded their indications across various cancer types and established themselves as a major pillar of cancer treatment. Whether the growing number of indications receive coverage has become an important gateway that determines treatment access.

The extent to which the clinical value of new treatment options should be reflected during reimbursement review remains a persistent concern. For the government, it is a matter of striking a balance between the financial burden and the clinical benefits offered by new drugs.

The upcoming Cancer Disease Deliberation Committee of the Health Insurance Review and Assessment Service is one place where this question constantly comes up for debate. At this month’s meeting, reimbursement for the ‘Opdivo (nivolumab)’ and ‘Yervoy (ipilimumab)’ combination as first-line treatment for hepatocellular carcinoma and non-small cell lung cancer will be presented for deliberation. At the meeting held last October, the combination was rejected for both liver and lung cancers.

In hepatocellular carcinoma, following Tecentriq (atezolizumab) plus Avastin (bevacizumab), Imfinzi (durvalumab) plus Imjudo (tremelimumab) have also been added to the reimbursement list. In non-small cell lung cancer as well, an immuno-oncology-based treatment strategy has already taken hold, with ‘Keytruda (pembrolizumab)’ already reimbursed as monotherapy and combination therapy for 4 years.

With immuno-oncology drug combinations already reimbursed, attention is now turning to whether reimbursement criteria will be set for the new Opdivo-Yervoy combination, as the addition must be more than simply another treatment option to pass review.

In this regard, hepatocellular carcinoma remains a cancer type with frequent recurrence, poor prognosis, and high mortality rates, and many patients begin treatment with impaired liver function. Due to these disease characteristics, key evaluation criteria include whether the treatment option can provide deep and durable responses, long-term survival, and long-term survival benefit regardless of liver function status.

The Opdivo and Yervoy combination is the treatment option that has demonstrated the longest survival data in first-line treatment for hepatocellular carcinoma. In clinical trials, it recorded a median overall survival (mOS) of 23.7 months, with a survival rate of 31% at 48 months. In addition, in an Asian patient subgroup analysis, a median overall survival (mOS) of 34.0 months, a 3-year survival rate of 49%, an objective response rate of 37%, and a complete response rate of 10% were reported. Compared with existing immuno-oncology combinations, whose mOS typically does not exceed 20 months, these are significant results.

In particular, the Opdivo-Yervoy combination significantly reduced the risk of death by 25% versus the control arm, even in patients with impaired liver function classified as ALBI grade 2/3, demonstrating a degree of mortality risk reduction comparable to that seen in patients with preserved liver function.

Its use in non-small cell lung cancer also warrants attention. Although Keytruda-based regimens have effectively become the cornerstone of first-line treatment, it is difficult to say that they fully address the treatment needs of all patient subgroups. In practice, there are still patient groups, such as those with PD-L1-negative tumors or squamous histology, for whom long-term survival benefit under existing immuno-oncology treatment settings has been reported only to a limited extent.

As the Opdivo-Yervoy combination demonstrates consistent survival improvements in these patient groups, regardless of PD-L1 expression or histology, it has been discussed as a viable alternative.

Ultimately, the core of the Cancer Disease Deliberation Committee review should not be on whether another option should be added to the reimbursement list. Real deliberation should be made on whether the current reimbursement system is offering a sufficient range of treatment choices in practice, and to what extent unmet treatment needs in specific patient groups should be reflected in deliberations. It would be difficult to accept a conclusion that the current system is sufficient merely because options already exist. When it comes to immuno-oncology drugs, unmet needs remain.