When the first immunotherapy drug proven to reduce the risk of kidney cancer recurrence was approved by the U.S. Food and Drug Administration (FDA) in November 2021, it marked a promising breakthrough for patients who have had surgery for tumor removal.
Until now, there has not been an approved adjuvant (after treatment) immunotherapy for renal cell carcinoma (RCC), the most common form of kidney cancer. RCC is a chemotherapy-resistant tumor, so in that regard, the FDA approval of pembrolizumab is a game-changer.
For the first time, patients who have an intermediate-high to high risk of kidney cancer recurrence have access to a treatment that helps the body detect and destroy cancer cells that may arise after surgery.
My colleagues and I at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center were thrilled to participate in the clinical study that led to the FDA approval of adjuvant pembrolizumab. In the KEYNOTE-564 trial, pembrolizumab was shown to reduce recurrence risk or death by 32%, compared to placebo. The trial also showed a larger percent of disease-free survival – 78.3% in the pembrolizumab compared with 67.3% in the placebo group at the two-year mark.
As early leaders in kidney cancer immunotherapy, we are cautiously optimistic about this inaugural treatment and its “curative potential.”
Yet we understand that immunotherapy after surgery may not be the best choice for everyone who has RCC. It’s a personal decision that requires a discussion with your care team and your family about the potential benefits and risks.
The side effects of immunotherapy, along with the commitment of time and acknowledgment of unknowns, are factors we typically discuss as you weigh this new treatment option. And as we continue to study the effectiveness of pembrolizumab, we will share these data with you to help guide your decisions about ongoing kidney cancer care.
How pembrolizumab after surgery works
Cancer can turn off the beneficial immune system “checkpoints” that protect against malignancy, tricking the body into allowing the cancer to mutate and spread. Immunotherapy infuses the patient with antibodies – proteins that seek and invigorate immune system cells, unleashing their full force onto the cancer.
Essentially, pembrolizumab infusions allow a patient’s immune system to defend their body against cancer. Called a PD-1 inhibitor, pembrolizumab blocks the PD-1 protein to boost the immune response against kidney cancer cells.
For kidney cancer, pembrolizumab is given intravenously (by infusion) every three weeks for a year. The infusions take approximately 30 minutes. For patients who choose to get immunotherapy at a specialized center such as UT Southwestern, one of the benefits is that our multidisciplinary kidney cancer team has the expertise to manage autoimmune side effects, particularly extreme reactions, which are rare.
Because immunotherapy alters your immune system, the side effects won’t resolve on their own and must be treated quickly to avoid escalation and further damage.
Potential side effects
Pembrolizumab is well-tolerated in most patients. During the trial, about 8% of patients required prednisone or other steroids to treat the side effects, and 20% had to cease the immunotherapy early because of them. The most common side effects include:
- Musculoskeletal pain
- Itchy skin
- Hypothyroidism – decreased thyroid function
Rarely, immunotherapy can trigger a severe autoimmune response that can cause inflammation of the liver, lungs, or colon, or irreversible conditions such as diabetes or adrenal insufficiency.
Related reading: Immunotherapy for kidney cancer: Using the body as a weapon
Deciding whether to start immunotherapy after surgery
While the potential benefits to pembrolizumab therapy are promising, the decision to start treatment is multi-faceted and personal. The alternative to immunotherapy following surgery is “active surveillance,” in other words closely monitoring you for the return of cancer. Each option comes with its own benefits and risks.
The FDA approved pembrolizumab therapy for the treatment of RCC patients after surgical resection of kidney cancer if they are considered at intermediate-high or high risk of recurrence. But the range of risk is wide. For example, if you have a 30% risk of the cancer returning, that means you have a 70% chance it never will. That’s a very different situation than if you faced a 70% risk of recurrence.
While part of your decision will be based on your risk of recurrence, some of it will depend on tolerance of potential side effects. Another factor may also be how far you live from a treatment center and whether you have the support system for the infusions.
Patients often ask what I would do if I were in their shoes. It really is a complex decision process, where a good understanding of the pros and cons – as well your own personal goals and personality – play a significant role.
As you are talking with your doctor about options, we strongly encourage you to bring family or a close friend along to your appointments. Every attendee will understand the conversation a little differently, and it helps to have another trusted perspective – and to help you remember all your questions and next steps.
Pembrolizumab has curative potential, meaning there is a possibility it could extend overall survival. However, it will be several years before we have enough data to be certain.
As we continue to receive data, we will hone our ability to determine which patients will likely benefit the most. In the meantime, we are grateful to be expanding the treatment options we can offer our patients after surgery for kidney cancer.