A new study out of France is looking at how effective it is to use a combination of nivolumab and ipilimumab immunotherapy drugs for mesothelioma after the patient received chemotherapy. Nivolumab alone has already shown promise in mesothelioma patients who have stopped responding to chemotherapy.

Chemotherapy is the first-line treatment for mesothelioma. However, it only helps around 35-41% of mesothelioma patients. There is currently no standard second-line treatment for patients if chemotherapy stops working, but this new study from France is looking to change that.

About the Phase 2 Trial

In this phase 2 trial, researchers are studying nivolumab and ipilimumab immunotherapy drugs for mesothelioma to determine whether or not the combination is a good follow-up treatment for patients who are finished chemotherapy. The researchers recruited patients whose tumors started growing after they underwent standard chemotherapy for mesothelioma.

The researchers then divided their patients into 2 groups:

  1. The first group received nivolumab alone
  2. The second group received both nivolumab and ipilimumab

The tests stopped once the patient’s tumor began to grow again or if the drug cocktail became too toxic and dangerous. The goal was that every patient would receive nivolumab 6 times and those who were receiving ipilimumab would get it twice in 3 months.

If at least 40% of their patients achieved and maintained disease control—that is, if their tumors did not grow larger—for the entirety of the 12-week study, then the researchers would consider their test successful.

Results of Nivolumab and Ipilimumab Trial

After 12 weeks passed, the researchers examined the first 108 of 125 eligible patients—54 of whom had only received nivolumab and 54 who received both nivolumab and ipilimumab.

In the nivolumab-only group, 44% of the patients did not show signs of tumor growth over 12 weeks. However, that number dropped to 40% when the information from the remaining participants was recorded.

As for the group who received both immunotherapy drugs for mesothelioma, 50% of the first 54 patients had disease control by the end of 3 months, and that number went up to 52% when the other patients were included.

While this means the researchers met their goal, the results weren’t achieved without any unexpected toxicity. Nine nivolumab-only patients and 16 combination-group patients had severe side effects. The most common side effect was a debilitating lack of energy, meaning several patients couldn’t maintain day-to-day activities while being treated.

For 3 combination-group patients, the side effects were deadly—although they had different causes of death.

Other studies have also looked at the combination of these two drugs. One study that was published in the Journal for ImmunoTherapy of Cancer determined that nivolumab and ipilimumab could be an excellent first-line treatment for advanced renal-cell carcinoma. Another study found the combination to be an effective first-line treatment for advanced melanoma.

How Nivolumab and Ipilimumab Work

Usually, when a person gets sick, their immune system is activated and white blood cells attack the invading organisms. However, cancer cells can trick the body into thinking there is nothing wrong, preventing the immune system from activating.

Nivolumab and ipilimumab are immunotherapy drugs for mesothelioma that wake the immune system up so the body can better fight cancer cells.

Nivolumab activates the immune system by bonding with a protein called programmed cell death-1 (PD-1). In a healthy person, PD-1 stops white blood cells from attacking other cells. Mesothelioma cells produce excessive PD-1 so the body can’t fight them. When nivolumab attaches to PD-1, it prevents the protein from bonding to white blood cells and shutting them down.

This study from France is not the first time that nivolumab has been tested in mesothelioma patients. In one case study, a 68-year-old man who had less than a year to live began nivolumab treatment. Thirty-six months after his first dose he was still active and in remission.

However, nivolumab does not always work on its own, which is why the researchers combined it with ipilimumab. The difference between ipilimumab and nivolumab is what they bond with. Ipilimumab attaches to a different substance—CTLA-4 protein receptor— to prevent white blood cells from being shut off and to help them recognize cancerous cells.

Because chemotherapy doesn’t fully treat most mesothelioma cases, it’s crucial for researchers to find second-line therapies that help relapsed patients without being overly toxic. Perhaps as researchers continue to look for these second-line treatments, they will discover ones that can work as a first-line treatment that work for more than half of mesothelioma patients.

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Sources
  1. "Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomized, non-comparative, phase 2 trial," The Lancet. Retrieved from: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30765-4/fulltext. Accessed January 30, 2019.
  2. "Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients (MAPS2)," ClinicalTrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02716272. Accessed January 30, 2019.
  3. "Nivolumab," Chemocare. Retrieved from: http://chemocare.com/chemotherapy/drug-info/Nivolumab.aspx. Accessed January 30, 2019.
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Last modified: February 27, 2019