Keytruda, the brand name for pembrolizumab, has been a source of hope for many people with mesothelioma.
At a recent medical conference, researchers revealed discouraging news about the immunotherapy drug’s effectiveness treating this disease on its own.
However, not all hope is lost for Keytruda as a viable mesothelioma immunotherapy.
Numerous experts in the field, from researchers to oncologists, still speak highly of Keytruda’s potential. They say that, if combined with other treatments, Keytruda could benefit mesothelioma patients now and well into the future.
“Don’t give up on immunotherapy,” said Dr. Ezra Cohen, a medical oncologist who treats pleural mesothelioma. “There is that initial disappointment. … It’s just a matter of figuring it out.”
How Keytruda Works for Mesothelioma
Keytruda is an immune checkpoint inhibitor, which in short means it props up the immune system. In more technical terms, Keytruda stops cancerous proteins from subduing the immune system.
Mesothelioma tumors include a protein called PD-L1. This protein interacts with the protein PD-1, which is found on the body’s T-cells. These cells are the immune system’s primary defenders against diseases such as cancer.
When the PD-L1 and PD-1 bind together, the T-cells become ineffective at recognizing mesothelioma tumors as dangerous to the body. Therefore, they do not actively fight the disease, and the cancer can spread with little to no opposition.
Keytruda is an anti-PD-L1 drug. It blocks the proteins’ interaction, which means the T-cells remain active and ready to fight the mesothelioma tumors.
“It still has a role,” Dr. Cohen said of Keytruda. “We’re learning more and more about who this entire class of drugs (immunotherapy) works in. We’re learning what we can combine it with to create better efficacy.”
Results from a Phase 3 Clinical Trial Involving Keytruda
The European Society of Medical Oncology (ESMO) conference last month included results from the Phase 3 PROMISE-pleural mesothelioma clinical trial. In the study, researchers compared Keytruda to standard mesothelioma chemotherapy (cisplatin and pemetrexed).
According to the Cancer Therapy Advisor website, 144 pleural mesothelioma patients enrolled and were divided into two groups. One group received only pembrolizumab, and the other received just chemotherapy.
The average overall survival for the pembrolizumab group was 10.7 months. For the chemotherapy group, the average survival time was 11.7 months.
In a press release posted on the ESMO website, study author Dr. Sanjay Popat called the results “disappointing.” He added that the immunotherapy drug didn’t “delay progression (of the cancer) or improve survival.”
However, Dr. Popat still believes Keytruda can treat mesothelioma. The drug just needs a little help.
Next Step: Combine Keytruda With Other Treatments
In the press release, Dr. Popat asked researchers to continue testing Keytruda in clinical trials. He believes early stage mesothelioma patients could benefit from immunotherapy more than those in the PROMISE trial, which included many people with late-stage pleural mesothelioma.
He also urged researchers to combine immunotherapy drugs like Keytruda with other treatments. For instance, chemoimmunotherapy is a common experimental approach in mesothelioma clinical trials.
“In studies of lung cancer,” Dr. Popat explained, “we have already learned that we can improve results with immunotherapy by combining it with chemotherapy, and the same may be true with mesothelioma.
“I would advise clinicians to enroll their patients into one of the large ongoing trials of first-line combination treatment so we can get answers as soon as possible about how to improve mesothelioma treatment.”
There have been quite a few mesothelioma clinical trials involving just this theory, and there are other active studies currently looking for patients:
- A pilot trial out of the University of Chicago is recruiting patients for a study involving Keytruda, chemotherapy and extended pleurectomy with decortication.
- A Phase 1 trial out of the Abramson Cancer Center at the University of Pennsylvania is combining Keytruda, chemotherapy and image-guided surgery.
- Dr. Cohen is leading a clinical trial at the University of California San Diego. The study combines Keytruda with an “individualized vaccine” to inhibit immune system response.
“The community needs to think about other strategies,” Dr. Cohen said. “Should there be a patient-selection strategy? Because not every patient responds the same way to pembrolizumab. Also, we need to look at (how to use the drug) in combination with other treatments.”
How to Join a Mesothelioma Clinical Trial
Many specialists suggest clinical trials to late-stage mesothelioma patients who can’t have surgery. However, these studies also could help people with early stage mesothelioma.
In fact, as Dr. Popat said, they could be more useful for people with a less-advanced form of the disease. So if you have early stage mesothelioma and are interested in joining a study that involves immunotherapy, then continue looking for one.
We at Mesothelioma Guide can even help you find the right trial. Our patient advocate and registered nurse, Karen Ritter, is the best resource for mesothelioma patients. She can find a study best suited for your disease. Email her at firstname.lastname@example.org for more about how immunotherapy trials can (still) help you and other mesothelioma patients.
- PembROlizuMab Immunotherapy Versus Standard Chemotherapy for Advanced prE-treated Malignant Pleural Mesothelioma (PROMISE-meso). U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02991482. Accessed: 10/08/19.
- Pembrolizumab Does Not Outperform Chemotherapy in Mesothelioma. Cancer Therapy Advisory. Retrieved from: https://www.cancertherapyadvisor.com/home/news/conference-coverage/european-society-for-medical-oncology-esmo/esmo-2019/mesothelioma-pembrolizumab-not-outperform-chemotherapy/. Accessed: 10/08/19.
- A Pilot Window-Of-Opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma. U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02707666. Accessed: 10/08/19.
- Pembrolizumab in Combination With Chemotherapy and Image-Guided Surgery for Malignant Pleural Mesothelioma (MPM). U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03760575. Accessed: 10/08/19.
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