[Desk’s View] OS still reigns supreme in reimb review

Overall survival (OS) continued to reign supreme. Two CDK4/6 inhibitors were reviewed at the same Cancer Drug Deliberation Committee (CDDC) meeting, yet they received very different outcomes. Verzenio, backed by OS data, passed reimbursement review, while Kisqali, which has yet to demonstrate mature OS data, failed to secure reimbursement criteria.

“No OS data, no CDDC approval” has effectively become an unwritten rule, especially in solid tumors. The debate over whether to recognize a class effect or uphold the primacy of overall survival (OS) ultimately appeared to end in favor of preserving OS as the decisive standard. Although the Ministry of Health and Welfare (MOHW) and the Health Insurance Review and Assessment Service (HIRA) continue to state that their decisions are based on a comprehensive assessment of clinical benefit, societal need, and budget impact, an analysis of the CDDC outcomes over the past three years suggests otherwise.

The latest decision also raises another important question. Unlike Verzenio, Kisqali sought reimbursement not only for node-positive patients but also for high-risk node-negative (N0) patients, making the outcome worthy of further discussion.

In early breast cancer, lymph node metastasis has long been regarded as one of the most important prognostic factors. However, the latest treatment paradigms no longer assess recurrence risk based solely on nodal status. The current standards evaluate multiple pathological risk factors, including tumor size (T stage), histologic grade, and the Ki-67 proliferation index, to determine an individual's risk of recurrence.

Indeed, some patients with high-risk N0 disease are known to have recurrence risks comparable to those of N1 patients with 1-3 positive lymph nodes. In other words, the absence of lymph node metastasis does not necessarily indicate a low risk of recurrence.

This change is already being reflected in major clinical trials. The NATALEE study evaluated adjuvant Kisqali therapy not only in node-positive patients but also in high-risk N0 patients, illustrating the shift in early breast cancer treatment from staging-based decisions toward more individualized and sophisticated assessments of recurrence risk.

Of course, OS will remain an important standard in the decision-making process. Long-term follow-up from adjuvant studies in early breast cancer continues to produce increasingly mature survival data. However, the objective of adjuvant therapy is not simply to prolong overall survival. It also aims to reduce recurrence, prevent distant metastasis, and keep patients from progressing to advanced breast cancer.

In this regard, the CDDC decision extends beyond reimbursement for a single drug and once again highlights the issue of treatment access for high-risk N0 patients. Because adjuvant therapy inherently requires longer follow-up to generate mature OS data, patients at high risk of recurrence may also face prolonged delays in accessing potentially beneficial treatment.

The European Society for Medical Oncology's Magnitude of Clinical Benefit Scale version 2.0 (ESMO-MCBS v2.0) allows improvements in disease-free survival (DFS) to be considered clinically meaningful in the adjuvant setting even before mature OS data become available. This does not diminish the importance of OS; rather, it acknowledges that preventing recurrence is itself a meaningful therapeutic benefit for patients.

The CDDC therefore continues to face an important challenge. While OS remains a critical source of evidence, can it alone fully capture a therapy's clinical value? Given that DFS is already recognized as a meaningful measure of clinical benefit in major assessment frameworks for adjuvant therapy, it is worth considering whether restricting patient access until mature long-term OS data become available truly represents the best policy decision.

When it takes years for OS data to mature, can patients afford to wait, and can we be certain that letting them wait is really the right answer?