Urothelial Carcinoma of the Urinary Bladder

Pictured: Merck's office in Canada/iStock, JHVEPhoto Merck on Friday released additional data from its Phase III KEYNOTE-A18 study, demonstrating that its blockbuster PD-1 inhibitor Keytruda (pembrolizumab) can significantly improve overall survival when used to treat patients with newly diagnosed high-risk locally advanced cervical cancer. Based on the findings of an Independent Data Monitoring Committee pre-specified interim analysis, Keytruda plus concurrent chemoradiotherapy (CRT) elicited a “statistically significant and clinically meaningful” improvement in overall survival (OS) in treated patients, compared with CRT alone. OS is one of the two primary endpoints in KEYNOTE-A18, along with progression-free survival (PFS). The study also found the Keytruda regimen to be safe overall and well-tolerated, with no new signals of concern. Merck did not reveal specific data in its announcement but promised to do so at an upcoming medical congress. The company said it will also share these findings with regulatory authorities. The results make KEYNOTE-A18 the “first Phase III trial” that has demonstrated a significant improvement after treatment with an “immunotherapy-based regimen,” compared with chemoradiotherapy alone, Gursel Aktan, vice president of global clinical development at Merck Research Laboratories, said in a statement. Friday’s readout comes after Merck in October 2023 presented PFS data from KEYNOTE-A18 at the European Society for Medical Oncology Congress. Patients treated with the Keytruda regimen saw a 30% drop in the risk of disease progression or death versus CRT alone after a median follow-up of 17.9 months. PFS at 24 months was 67.8% in the Keytruda combo arm and 57.3% in the control group. Taken together, the PFS and OS data demonstrate the potential of using Keytruda in earlier stages of cancer, “where there is a greater potential for better outcomes,” Aktan said. Keytruda is a humanized monoclonal antibody that works by interrupting the interaction with the PD-1 receptor and its corresponding ligands. This mechanism of action prevents cancer cells from evading the body’s anti-cancer immune response. The PD-1 inhibitor was first approved in 2014 in advanced melanoma, but has since picked up several other indications in oncology and has become a cornerstone therapy in the field. The blockbuster has two approved indications in cervical cancer. The first is as a combo treatment with chemotherapy, with or without Roche’s Avastin (bevacizumab), for the treatment of persistent, recurrent or metastatic disease. The second is as a monotherapy for metastatic or recurrent cervical cancer that has progressed following chemotherapy. In January 2024, Merck posted back-to-back late-stage victories for Keytruda in kidney and bladder cancer. The PD-1 inhibitor improved overall survival as an adjuvant treatment in renal cell carcinoma and led to significantly better disease-free survival in patients with muscle-invasive urothelial carcinoma. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Pictured: Merck Research Laboratories in California/iStock, Michael Vi Merck‘s blockbuster Keytruda (pembrolizumab) continues to be a top seller for the pharma giant as it posted over $25 billion in sales in 2023, a 19% jump from last year, according to the company's fourth quarter and full-year financial results announced on Thursday. According to Merck’s fourth-quarter 2023 results, Keytruda pulled in over $6.6 billion in sales, a 21% bump from the same period in 2022. The sales growth in the quarter was due to an “uptake in earlier-stage indications” such as in renal cell carcinoma and triple-negative breast cancer, along with the global demand for its other multiple indications. The company’s HPV vaccine Gardasil also reached the billion-dollar figure in the fourth quarter of 2023, bringing in $1.8 billion for Merck in 2023, a 27% jump from the previous year due to growth in the U.S. and China. For all of 2023, Gardasil brought in over $8.8 billion. However, Merck’s COVID-19 did not fare well. The antiviral Lageviro posted $193 million in sales in the fourth quarter of 2023, a 77% drop from last year. Merck said this was due to a “nonrecurrence” of sales in the U.K. and low demand in Australia and Japan. It only brought in over $1.4 billion for 2023, a 75% drop since 2022. Still, pharmaceuticals pulled in over $13 billion in sales for Merck in the fourth quarter of 2023, an 8% jump since last year, and $60 billion in total for the year. “2023 was another solid year for Merck. I am extremely pleased by the progress we’ve made to develop and deliver transformative therapies and vaccines that will help save and improve lives worldwide,” Merck CEO Robert Davis said in a statement. Merck is continuing its clinical program in 2024 for blockbuster cancer drug Keytruda. In January, one of Keytruda’s latest data rollouts showed an improvement in overall survival when used as an adjuvant treatment in renal cell carcinoma and for localized muscle-invasive urothelial carcinoma. The company last month acquired Harpoon Therapeutics for $680 million to add to its oncology and immunotherapy pipeline. Merck is also looking to target the competitive pneumococcal vaccine space, with a PDUFA date set for its V116 vaccine in June 2024. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Merck & Co – known as MSD outside the US and Canada – has shared positive results from a late-stage study of Keytruda (pembrolizumab) in a subset of bladder cancer patients. The phase 3 AMBASSADOR/KEYNOTE-123 trial has been evaluating the anti-PD-1 therapy as an adjuvant treatment for high-risk patients with localised muscle-invasive urothelial carcinoma and locally advanced resectable urothelial carcinoma. According to the results presented at this year's American Society of Clinical Oncology Genitourinary Cancers Symposium, Keytruda demonstrated a statistically significant and clinically meaningful improvement in one of the study’s dual primary endpoints of disease-free survival (DFS) after a median follow-up of 22.3 months, reducing the risk of disease recurrence or death by 31% versus observation in these patients after surgery. The trial’s second dual primary endpoint of overall survival did not reach statistical significance at the time of the pre-specified interim analysis and will continue to be followed as data mature, Merck said. Approximately 83,000 people in the US are expected to be diagnosed with bladder cancer this year, with muscle-invasive bladder cancer accounting for up to 25% of new cases. Muscle-invasive bladder cancer is a form of the disease that has spread into the deep muscle of the bladder wall, while locally advanced urothelial cancer is a cancer that begins in the urothelial cells and has spread to nearby tissue or lymph nodes. Despite surgery, up to 50% of patients with muscle-invasive bladder cancer experience recurrence within 12 months. Dr Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said: “This phase 3 data marks the first time Keytruda has shown a clinically meaningful improvement in DFS as adjuvant therapy in urothelial carcinoma. “Results from this pivotal study support Keytruda as a potential new adjuvant option for these patients and demonstrate the expanding role of Keytruda into earlier stages of resectable muscle-invasive bladder cancer.” Keytruda works by increasing the ability of the body’s immune system to help detect and fight tumour cells. The therapy already holds approvals to treat a wide variety of cancers, including specific cases of locally advanced or metastatic urothelial carcinoma and non-muscle-invasive bladder cancer. There are also currently more than 1,600 trials studying Keytruda, including the phase 3 KEYNOTE-564 study that has been evaluating the therapy in a subset of kidney cancer patients.