Keytruda’s bladder cancer expansion expected to fill treatment gap

Its use in combination with Padcev approved… improves key clinical endpoints

New perioperative option added for cisplatin-ineligible MIBC patients

A new perioperative treatment option has become available for patients with muscle-invasive bladder cancer (MIBC) who are unable to receive cisplatin-based chemotherapy.

With the combination of Keytruda (pembrolizumab) and Padcev (enfortumab vedotin) approved for use before and after radical cystectomy, a systemic treatment option aimed at reducing the risk of recurrence became available for cisplatin-ineligible patients who previously had to rely largely on surgery.

On the 2nd, MSD Korea held a press conference at JW Marriott Hotel Seoul to mark the approval of perioperative Keytruda in MIBC and present results from the Phase III KEYNOTE-905 trial and their implications for clinical practice in Korea.

In July, the Ministry of Food and Drug Safety approved Keytruda in combination with Padcev for neoadjuvant treatment before surgery and adjuvant treatment following radical cystectomy in patients with MIBC who are ineligible for cisplatin-containing chemotherapy.

Cisplatin-ineligible MIBC patients lacked perioperative treatment options

InKeun Park, Professor of Oncology at Asan Medica Center

MIBC is a stage of bladder cancer in which the tumor has invaded the muscular layer of the bladder, with radical cystectomy forming the cornerstone of treatment. Cisplatin-based chemotherapy has been recommended before surgery to reduce the risk of recurrence.

However, bladder cancer disproportionately affects older patients, many of whom have comorbidities such as impaired renal function, hearing loss, or peripheral neuropathy that make cisplatin unsuitable.

Systemic treatment options before surgery have been particularly limited for cisplatin-ineligible patients. With the risk of recurrence persisting even after radical surgery, there has been a longstanding unmet need for treatment strategies spanning both the pre- and postoperative settings. This perioperative treatment gap in cisplatin-ineligible MIBC patients was also cited as a key clinical consideration when the indication was approved in Korea.

Inkeun Park, professor of oncology at Asan Medical Center, said, “Radical cystectomy is critical in MIBC, but surgery alone cannot eliminate all risk of recurrence. Treatment options before surgery have been particularly limited for patients who cannot receive cisplatin-based neoadjuvant chemotherapy because of advanced age or impaired renal function.”

“These patients needed a treatment strategy that could reduce tumor burden before surgery and provide systemic control of micrometastatic residual disease through the postoperative period,” he added.

Risk of recurrence, progression, or death falls 60%...overall survival also improved

KEYNOTE-905 is a Phase III trial involving 344 patients with MIBC who were either ineligible for or declined cisplatin-based chemotherapy. The trial compared perioperative Padcev plus Keytruda with radical cystectomy alone.

Patients in the combination arm received 3 cycles of Keytruda plus Padcev before radical cystectomy, followed by 6 cycles of Keytruda plus Padcev after surgery and subsequent Keytruda monotherapy.

The combination reduced the risk of an event in event-free survival (EFS) by 60% compared with surgery alone. In the overall survival (OS) analysis, it also reduced the risk of death by 50%.

A marked difference was also observed in pathological complete response (pCR), which was achieved in 57.1% of patients in the combination arm compared with 8.6% in the surgery-alone arm.

Park said, “What is meaningful is not only the higher pathological complete response rate with preoperative treatment, but that the study also demonstrated improvements in the long-term clinical endpoints of EFS and OS. The findings provide evidence that perioperative systemic therapy can reduce the risks of recurrence and death even in patients who cannot receive cisplatin.”

Combination therapy moves from metastatic disease into curative-intent setting

Padcev plus Keytruda first demonstrated efficacy in locally advanced or metastatic urothelial carcinoma. Its development has since moved earlier into resectable MIBC, extending the combination from the metastatic setting into curative-intent treatment.

In MIBC in particular, evidence for Padcev plus Keytruda continues to build in both cisplatin-ineligible and cisplatin-eligible patients.

In KEYNOTE-B15, which enrolled cisplatin-eligible patients, perioperative Padcev plus Keytruda reduced the risk of an EFS event by 47% and the risk of death by 35% compared with conventional neoadjuvant gemcitabine plus cisplatin. The combination is currently under regulatory review in Korea for this indication.

Treatment options for MIBC are therefore becoming increasingly differentiated according to patients’ cisplatin eligibility and risk of recurrence, moving beyond a treatment paradigm centered on radical cystectomy toward one that incorporates perioperative systemic therapy.

Park said, “Since systemic therapy is administered both before and after surgery, drug treatment and surgery need to be planned as a single continuum of care. Treatment plans should take into account the patient’s renal function and overall condition, with close monitoring of adverse events during treatment and postoperative recovery to ensure that perioperative therapy can be continued appropriately.”