Mesothelioma experts continue to experiment with immunotherapy. Some specialists use the drugs before the primary treatment, some use them after and some even compare pairing them with surgery versus chemotherapy.
One clinical trial is testing all of the above: immunotherapy before and after both surgery and chemotherapy.
The study is titled “Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma”. It will use an immunotherapy drug pairing prior to and following the standard of care for pleural mesothelioma. The immunotherapy drugs are nivolumab (also called by its brand name Opdivo) and ipilimumab (called Yervoy).
Dr. Patrick Forde is a thoracic oncologist at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland. He joined the Meet the Mesothelioma Experts podcast series two weeks ago to discuss this promising clinical trial.
“It’s building on some work that has been done for other types of cancer,” Dr. Forde said during the podcast.
How You Can Enroll
There are multiple parts of the trial, which uniquely utilizes immunotherapy twice. In sequential order, the study’s stages are:
- Chemotherapy (optional)
There are few requirements or exclusions for enrolling in the trial. Patients must have pleural mesothelioma and be surgical candidates, which usually means either a Stage 1, Stage 2 or Stage 3 disease.
Patients also must have either epithelioid pleural mesothelioma or biphasic pleural mesothelioma. Sarcomatoid patients are not eligible.
The clinical trial is currently enrolling at three locations:
- Greenebaum Comprehensive Cancer Center (Baltimore)
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- University of Texas MD Anderson Cancer Center (Houston)
If you’re interested in joining the study, contact our patient advocate and registered nurse, Karen Ritter. She can answer if you’re eligible for the clinical trial and explain your affordable travel options to receive treatment at one of the three hospitals. Please email her at firstname.lastname@example.org for help.
What Patients Will Receive in the Trial
The chief aspect of the study involves “neoadjuvant” immunotherapy, which is a medical term for immunotherapy administered prior to surgery.
The trial has 30 spots available. The first 15 enrollees will receive three dosages of nivolumab in a four-week span: one each at the six-, four- and two-week marks before surgery.
The last 15 enrollees will receive the same schedule of nivolumab. The only difference is they’ll also receive one dose of ipilimumab six weeks before surgery.
“Giving immunotherapy prior to surgery has shown to lead to a regression of the tumor and to an infiltration of the immune system attacking the cancer,” said Dr. Forde, who specializes in treating lung cancer, mesothelioma and other thoracic diseases.
The next step is undergoing one of the two curative surgeries for pleural mesothelioma: extrapleural pneumonectomy or pleurectomy with decortication. Dr. Forde said both are suitable options for this trial, but patients must undergo at least one. The combination of neoadjuvant immunotherapy and surgery is the critical component the research team will analyze.
Following surgery, patients are recommended to receive up to four rounds of chemotherapy (either cisplatin or pemetrexed). Dr. Forde said enrollees may opt-out of chemotherapy if they choose. However, it could affect the participants’ chances of long-term survival.
“We’re not necessarily saying chemotherapy isn’t a good idea,” Dr. Forde said after mentioning chemotherapy’s well-known side effects of nausea, fatigue and low blood count. “It could actually be something that works well sequentially or with immunotherapy. This trial does incorporate that.”
Following surgery and potential chemotherapy, patients can pick up their immunotherapy treatment. Participants can receive a monthly dose of nivolumab for up to one year. Receiving this treatment following surgery is called “adjuvant” immunotherapy.
Why Immunotherapy Could Be the Future of Mesothelioma Treatment
We should expect more clinical trials involving immunotherapy to start. The end goal is for one study — or multiple studies — to find the right formula and receive approval from the U.S. Food and Drug Administration.
This rare and aggressive cancer is comprised of many microscopic tumors, each with diseased cells that form due to asbestos exposure. These cells include PD-L1 proteins, which have receptors that are solely responsible for why the immune system needs help fighting mesothelioma.
The immune system’s T cells have PD-1 proteins, which also have receptors. When the PD-L1 receptors merge with the PD-1 receptors, the T cells incorrectly assume the mesothelioma cells are harmless. The PD-L1 receptor serves as a mask for the disease, which then can spread unchecked throughout the body.
Immunotherapy drugs like nivolumab act as a wall between the receptors — blocking them from interacting. The immune system then identifies mesothelioma cells as dangerous and goes on the attack.
Ipilimumab targets a different protein receptor, CTLA-4, which down-regulates the immune system. CTL, the acronym for cytotoxic T lymphocytes, is a white blood cell that targets cancer cells. The protein receptor subdues the white blood cells’ attack mindset, but ipilimumab negates CTLA-4 and allows the white blood cells to work effectively.
“These medicines really have become broadly used in the last five or six years,” Dr. Forde said, later adding that they “are well-tolerated” with few side effects.
By enrolling, you’ll also be helping doctors better understand how immunotherapy drugs affect mesothelioma tumors. Since immunotherapy occurs before surgery, the medical team can inspect the removed tumors to analyze how they responded to nivolumab and ipilimumab.
“Because the tumors will be removed at the time of surgery,” Dr. Forde said, “we’ll be able to look at the tumors and see how they responded to immunotherapy.”
Sources & Author
- Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma. Clinicaltrials.gov. Retrieved from:
https://clinicaltrials.gov/ct2/show/NCT03918252. Accessed: 02/18/2020.
- Pre-Operative Immunotherapy Clinical Trial with Dr. Patrick Forde of Johns Hopkins. Mesothelioma Applied Research Foundation. Retrieved from: https://www.curemeso.org/get-involved/attend-conferences-and-events/meet-the-mesothelioma-experts-podcast-broadcast-series/pre-operative-immunotherapy-clinical-trial-with-dr-patrick-forde-of-johns-hopkins/. Accessed: 02/18/2020.
Sources & Author