‘Padcev + Keytruda’ reimbursement imminent in KOR

Signals a shift in Korea’s bladder cancer treatment landscape

Passes DREC review… 6 months after passing CDDC review

Attention rises on shift in treatment focus toward ‘Bavencio’ maintenance therapy

Immunotherapy ‘Keytruda’ and ADC ‘Padcev

With combination therapy using antibody-drug conjugates (ADCs) and immuno-oncology drugs on the verge of being reimbursed in Korea, the treatment landscape for bladder cancer (urothelial carcinoma) is increasingly likely to undergo a structural shift.

According to industry sources, the Health Insurance Review and Assessment Service (HIRA)’s Drug Reimbursement Evaluation Committee recognized the appropriateness of reimbursement for the combination therapy of Padcev and Keytruda as a first-line treatment for adults with locally advanced or metastatic urothelial carcinoma on April 2. Padcev monotherapy, however, did not receive reimbursement approval.

This decision comes approximately 6 months after the combination regimen passed the Cancer Drug Deliberation Committee last October. If price negotiations with the National Health Insurance Service (NHIS) are concluded successfully, Padcev + Keytruda will be listed for reimbursement.

Padcev is an ADC that targets Nectin-4, comprised of a fully human anti-Nectin-4 immunoglobulin G1 kappa monoclonal antibody conjugated to the small molecule microtubule-disrupting agent monomethyl auristatin E (MMAE), via a protease-cleavable maleimidocaproyl valine-cituline (vc) linker. Its mechanism of action involves selectively binding to tumor cells, internalization, and the release of MMAE via proteolytic cleavage, which subsequently induces cell death.

Its key feature is the expected synergistic effect when used in combination with PD-1 inhibitors. This mechanism maximizes antitumor efficacy by simultaneously inducing direct cytotoxicity via MMAE and immune activation.

These mechanistic strengths have also been confirmed in clinical trials. In the EV-302/KEYNOTE-A39 Phase 3 study, the combination therapy of Padcept and Keytruda achieved a median overall survival (OS) of 31.5 months in treatment-naïve urothelial carcinoma patients. This figure is approximately double that of the chemotherapy group, which recorded 16.1 months.

Based on these results, the National Comprehensive Cancer Network (NCCN) recommends Padcev + Keytruda as a Category 1 preferred first-line regimen, positioning it as an  option capable of replacing existing immuno-oncology drug + chemotherapy focused treatment strategies.

ADC + Immuno-oncology drugs take center stage… shifts maintenance therapy-centric structure

If the Padcev + Keytruda combination regimen is actually reimbursed, there is a high likelihood that the combination could shift the treatment axis in urothelial carcinoma.

Currently, various options coexist in the first-line treatment setting for urothelial carcinoma, including the combination of ‘Opdivo (nivolumab)’ and GemCis (gemcitabine + cisplatin) and the ADC + immuno-oncology drug combination.

In addition, a sequencing strategy, which involves maintenance therapy with Merck’s ‘Bavencio (avelumab)’ after chemotherapy, has also established itself as a major pillar. Among the therapies, Bavencio is currently the only reimbursed option.

Merck has emphasized adopting a sequencing strategy in which Bavencio maintenance therapy is administered after chemotherapy, followed by Padcev upon disease progression.

In fact, real-world data (RWD) from multinational studies such as Japan’s JAVEMACS, the U.S.’s PATRIOT-II, and France’s AVENANCE showed that the median overall survival (OS) with Bavencio maintenance therapy exceeded 30 months, with some analyses reporting survival extended to over 40 months.

Furthermore, in strategies where ADC is used following Bavencio maintenance therapy, OS exceeded 41 months, supporting long-term survival through sequential treatment.

Ultimately, the future treatment landscape is likely to evolve into competition between potent combination therapy in the first-line setting and maintenance-based sequencing strategies.

Whether or not reimbursement is approved is expected to serve as a key factor that goes beyond the simple addition of a treatment option. It is likely to reshape the very paradigm of bladder cancer treatment.