More urothelial cancer drug options now available in KOR

How will the increased first-line treatment options affect the treatment landscape?

Padcev+Keytruda is approved in the first line following the approval of the Opdivo combination therapy

Implications of expanding drug options in the first-line, which was previously centered around platinum-based chemotherapy

Cost huddle exists for immuno-oncology + ADC combinations... reimbursement approval will serve a key role

A number of immuno-oncology and antibody-drug conjugate (ADC) drugs are being granted approval as a first-line treatment of urothelial cancer, increasing the treatment options that had previously been dominated by platinum-based chemotherapy.

 

Although they are not yet reimbursed and have yet to become mainstream treatment options, it is expected that the strategy for each line of treatment will change in the long term.

 

(from left to right) Pic of Padcev, Keytruda, Opdivo

Urothelial carcinoma starts in the epithelial cells lining the urinary tract and is the most common type of bladder cancer, accounting for 90% of all bladder cancer diagnoses.

 

However, unlike other cancers like lung and breast cancer, where the standard of care changes quickly with the introduction of new drugs, UC has remained a barren area for decades, leaving a large unmet need for first-line treatment options.

 

For the past 30 years, platinum-based chemotherapy has remained the first-line standard of care for UC.

 

The introduction of Opdivo (nivolumab) has changed the situation.

 

The drug was approved by the Ministry of Food and Drug Safety on the 17th as a first-line treatment for unresectable or metastatic urothelial carcinoma in combination with cisplatin and gemcitabine (GemCis).

 

The approval was based on results from the Phase III CheckMate 901 trial in patients with unresectable or metastatic UC who had not received prior therapy.

 

  Results showed that at a median follow-up of 33.6 months, the primary endpoint, median OS (mOS), was 21.7 months with the use of the Opdivo+GemCis combination, which is significantly longer than the 18.9 months in the GemCis only arm, and reduced the risk of death by 22%.

 

In particular, the CheckMate-901 pivotal trial, which is evaluating Opdivo in combination with Yervoy (ipilimumab) versus the standard of care, leaves room for further expansion of Opdivo’s indications.

 

Keytruda (pembrolizumab) + Padcev (enfortumab vedotin), which received approval from the MFDS on March 2 5 following Opdivo’s approval, is also expected to rise as a first-line treatment option in UC.

 

Highlighted as a novel combination of an immuno-oncology drug and an ADC, the Keytruda-Padcev combination gained approval as the first treatment to change the first-line treatment paradigm for UC in 30 years when the first data were presented at the European Society for Medical Oncology Annual Meeting (ESMO 2023) last year.

 

The Phase III EV-302/KEYNOTE-A39 trial, which became the basis of its approval, the combination demonstrated a median progression-free survival (PFS) of 12.5 months over a median follow-up of 17.2 months, with a 55% reduction in the risk of disease progression and death compared to 6.3 months in the placebo arm.

 

Dr.

 

Jae-Lyun Lee, Professor of Medical Oncology at Seoul Asan Medical Center, said, “No other treatment in UC has shown this level of efficacy in the past 30 years.

 

The more than twofold increase in progression-free survival is truly remarkable, which is why we have high hopes for the Keytruda-Padcev combination.

 

Based on the clinical trial results, Padcev+Keytruda is expected to rise to the forefront among first-line treatment options on-site.

 

Currently, Bavencio (avelumab) is reimbursed as a first-line maintenance therapy, but as new first-line treatment options become available, a change in the treatment regimen and later-line therapies is inevitable.

 

However, Opdivo, which was added to existing first-line treatment options, and Keytruda+Padcev, an immuno-oncology drug, and an ADC combination, both are yet to be reimbursed in Korea, leaving the high cost an issue.

 

Dr.

 

Inho Kim, professor of Medical Oncology at St.

 

Mary's Hospital in Seoul, said, “Drugs like Padcev have shown good results recently, and I think each drug has its pros and cons.

 

Cost is also a consideration, and as we gain more prescription experience and accumulate more information on the patients’ conditions, we will be able to set guidelines for this.”