The FDA has approved a new combination therapy that uses two different types of anticancer medicines for treating adults with muscle-invasive bladder cancer (MIBC) who can’t receive cisplatin, a common chemotherapy drug.The approved combination includes the programmed death receptor-1 (PD-1) blocker Keytruda (pembrolizumab) or its under-the-skin injectable version Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) along with an antibody-drug conjugate, Padcev (enfortumab vedotin).This is the first time an immunotherapy medicine (Keytruda) and an antibody-drug conjugate (Padcev) have been approved together for use before and after bladder removal surgery.
Keytruda helps your immune system find and attack cancer cells, whereas Padcev is a targeted therapy that attaches to specific proteins on the cancer cells and delivers cancer-fighting medicine directly inside them.
MIBC is a serious type of bladder cancer that grows into the muscle wall and can spread quickly.
Even after surgery, about half of the people with MIBC see their cancer come back. Until now, there were few treatment options for people who couldn’t take or didn’t want cisplatin chemotherapy. This approval matters as this new combination may help improve outcomes for people who haven’t had new options in many years.
Why Was It Approved? The FDA approved this treatment based on a clinical study that showed that the combination of Keytruda and Padcev given before and after surgery, versus surgery alone, helped people live longer and stay cancer-free for a longer period. In a large phase III study involving 344 patients with MIBC who were unable to receive cisplatin, treatment with the Keytruda plus Padcev combination before and after surgery, versus surgery alone, reduced the risk of cancer recurrence or worsening by 60% and lowered the risk of death by 50%. At the time of the analysis, for people on the combination treatment, median survival times had not yet been reached, while the surgery-only group had a median event-free survival of 15.7 months and a median overall survival of 41.7 months. The study also showed that more patients had no cancer left after treatment with this combination therapy than after surgery alone (57% vs. 9%). Side effects were similar to those seen in earlier studies.
The effectiveness of Keytruda Qlex is supported by strong data from studies on Keytruda and other data showing that Keytruda Qlex works and behaves in the body similarly to Keytruda. The most common side effects of the combination treatment include hair loss; weight loss; diarrhea; constipation; swelling in the arms, hands, legs, or feet; rashes; itching; dry skin; decreased appetite; dry eyes; nausea; changes in taste; dizziness; fatigue; urinary tract infections; joint pain; low sodium, phosphate, protein (albumin), and hemoglobin levels; low white blood cell counts; high blood sugar and calcium levels; either high or low potassium levels; changes in liver enzyme levels and kidney test results; and increased levels of lipase (a pancreatic enzyme). Both Keytruda and Padcev can cause serious side effects. These include immune-related problems that may affect your lungs, liver, intestines, kidneys, hormones, thyroid, and skin. Some people may have severe reactions during the infusion. What Do I Need to Know? This treatment is given in two parts: before and after surgery. Before surgery (the neoadjuvant phase), you’ll get Keytruda via an intravenous (IV) infusion every three weeks. Also, Keytruda Qlex may be given as an under-the-skin injection in the thigh or belly area, offering more flexibility in how you receive treatment. You’ll get Padcev on days one and eight of each three-week cycle. This part lasts about nine weeks.After surgery (the adjuvant phase), you’ll continue with the same combination for another 18 weeks. After that, you may keep getting Keytruda alone for up to 42 weeks. Your health care provider will do blood tests to check your blood cell counts and liver, kidney, and thyroid function before and during your treatment. Before starting the treatment, tell your health care provider if you are allergic to Keytruda, Keytruda Qlex, Padcev, or any of their ingredients and about all your medical conditions, especially if you have numbness or tingling in your hands or feet, diabetes or high blood sugar levels, liver problems, or immune or nervous system disorders; or if you have had organ, tissue, or donor stem cell transplants (including corneal graft), or chest radiation. Also tell them about all medications, vitamins, and herbal supplements you take, as some may increase the risk of side effects.
Both medicines can harm a fetus, so you will need a pregnancy test before treatment and must use effective birth control: women for two months after the last Padcev dose and four months after the last Keytruda dose, and men with partners who can become pregnant should use birth control for four months after the last Padcev dose. Do not breastfeed during treatment; wait at least three weeks after the last Padcev dose and four months after the final Keytruda dose. Call your health care provider right away if you have coughing or trouble breathing; severe diarrhea, extreme tiredness; rash or blistering or peeling of the skin; painful sores or ulcers in the mouth or nose, throat, or genital area; dark urine; or yellowing of your skin or eyes. Your provider may pause or stop treatment and give you steroids to help manage side effects.
