The Food and Drug Administration’s approval of Keytruda in recurrent locally advanced or metastatic esophageal squamous cell carcinoma led to new progress for this patient population.
BY Kristie L. Kahl
The Food and Drug Administration (FDA)’s approval of Keytruda (pembrolizumab) for recurrent locally advanced or metastatic esophageal squamous cell carcinoma offers a new treatment option with less side effects.
Of note, this is the first anti-PD-1 therapy approved for the treatment of previously-treated patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1, a protein that helps keep immune cells from attacking nonharmful cells in the body.
“This is a new, exciting option for patients with esophageal squamous cell cancer,” Dr. Sarbajit Mukherjee, an assistant professor in the Department of Medicine - GI Medical Oncology at Roswell Park Comprehensive Cancer Center, said in an interview with CURE
“Typically, when patients progress after first-line treatment, they are treated with taxane- or irinotecan-based chemotherapy; however, the overall outcomes remain poor. Now, some of our (esophageal squamous cell cancer) patients can expect to have a treatment option that may help them live longer with possibly less side effects from treatment.”
Esophageal Squamous Cell Carcinoma
Esophageal squamous cell carcinoma – which usually begins in the cells that line the inside of the esophagus – is the sixth most common cause of cancer deaths worldwide. With this, squamous cell carcinoma – which involves the flat, thin cells that line the surface of the esophagus and occurs most often in the upper and middle portions of the organ – is the most prevalent type of this disease worldwide.
Treatment options for esophageal squamous cell carcinoma include surgery; radiation; chemotherapy; chemoradiation; targeted therapy, such as Herceptin (trastuzumab; and endoscopic treatments.
Efficacy and Safety
The FDA’s approval was based on data from two trials:
- KEYNOTE-181: a multicenter, randomized, open-label, active-controlled trial that enrolled 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced disease.
- KEYNOTE-180: a multicenter, non-randomized, open-label trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease.
While both trials demonstrated improved survival among patients, Keytruda – an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells – also appeared to be well tolerated.
Immune-mediated side effects included pneumonitis (inflammation of the lungs), colitis (inflammation of the inner lining of the colon), hepatitis, endocrinopathies (a disease of the endocrine gland), nephritis (a disease that injures the kidney) and renal dysfunction, severe skin reactions, solid organ transplant rejection and complications of allogeneic hematopoietic stem cell transplantation.
“The really nice thing is that pembrolizumab is very well tolerated so many patients who have difficulty tolerating chemotherapy may be able to handle this medication,” Dr. A. Craig Lockhart who is a professor of medicine and chief for the Division of Medical Oncology at the University of Miami – Sylvester Comprehensive Cancer Center.
Historically, patients with advanced esophageal cancer had limited treatment options: “This is very important as the treatment options for these patients are limited and we have not had many new recent treatment advances for these patients,” Lockhart, who is also a board member for the Esophageal Cancer Action Network (ECAN), said.
Mukherjee, who is also a board member for ECAN, agreed, adding that there is a need to develop more treatment options for these patients. “We must remember that immune checkpoint inhibitors like Keytruda benefit a minority of patients with esophageal cancer,” he added. “This emphasizes the need for a better patient selection strategy based on biomarkers as well as conducting further clinical trials with novel agents.”
With this, Mukherjee recommends for patients to join clinical trials to help further research and provide more treatment options for the future.
“I would always encourage patients to ask their doctors about potentially participating in clinical trials,” he said. “Esophageal cancer is a deadly disease but scientists and physicians around the globe are working to defeat this cancer. In coming years, I would expect to see (immune checkpoint inhibitors) being approved and used earlier during the treatment course.”
Moreover, the next goal will be to determine which patients to specifically treat with Keytruda.
“Approval of pembrolizumab is a great step forward and most experts expect that we will continue to make progress in the application of immune therapy drugs to the treatment of these cancers,” Lockhart said. “We will learn to better predict which patients are most likely to respond, we will see new combinations of immune therapies, including vaccines and cellular therapy options are under investigation.”
To read more about the approval
, read our original coverage from last week.