Webinar Recap: Mesothelioma Chemotherapy vs. Immunotherapy

• by Dr. Jennifer M. Suga
• Sep 16, 2022

I recently held a webinar for The Mesothelioma Center focused on the differences between chemotherapy and immunotherapy for mesothelioma.

The webinar was an excellent opportunity to review the most common mesothelioma drugs, how these treatments benefit patients, and what to expect during therapy. I also had the chance to answer questions during a live Q&A from viewers in attendance. 

Several participants provided great feedback stating how helpful the information was. A webinar recording is available via the registration page. 

I’ve written a review and recap of the essential topics covered in the informational session, along with additional details that viewers may have missed. 

Most Common Mesothelioma Chemotherapy Drugs

Lung cancer chemotherapy drugs have historically influenced which drugs we use for mesothelioma. In general, chemotherapy drugs disrupt the division of cells that divide quickly, preventing cancer cells from replicating and growing.

The platinum drugs, including cisplatin and carboplatin, have shown benefits for many different types of cancers for decades. Cisplatin has been preferentially used in mesothelioma clinical trials so there is more information regarding its usefulness in the treatment of mesothelioma. However, carboplatin is a comparable alternative with fewer side effects.

Doctors often pair platinum drugs with pemetrexed, known by its brand name Alimta. Pemetrexed is thought to be the most active mesothelioma chemotherapy drug, and it’s approved by the U.S. Food and Drug Administration specifically for mesothelioma. 

Combining pemetrexed with platinum drugs showed over 20% improvement in treatment response with more growth control and survival time. 

Gemcitabine, or Gemzar, is another chemotherapy drug for mesothelioma that can be given alone or in combination with platinum drugs. Gemcitabine is often more effective as a second- or third-line option after other treatment options have failed. 

Vinorelbine, or Navelbine, is a mesothelioma chemotherapy drug best used alone that typically has fewer symptoms than other chemotherapy options. Gemcitabine and vinorelbine have similar side effects of nausea, low blood count, neuropathy and liver toxicity. 

Angiogenesis and Vascular Drugs

Angiogenesis is the process of formation and maintenance of new blood vessels. Your tissues require new blood vessels for viability and growth. 

However, cancer uses this mechanism to grow and spread through the body. Mesothelioma cells have high levels of the VEGF receptor, which, when blocked, can reduce the rate of new blood vessels on tumors and restrict growth. 

Bevacizumab, also known as Avastin, is an anti-angiogenesis drug that blocks VEGF and works best in combination with chemotherapy. However, patients with certain conditions are not good candidates to receive bevacizumab.

The MAPS study showed that adding bevacizumab with cisplatin and pemetrexed decreased the death rate by 24% over 39 months. 

Targeting the Immune System

One of the most exciting advancements in mesothelioma treatment has been harnessing the immune system to fight cancer cells. 

Cancer cells have evolved in many ways to avoid the immune system. By expressing the protein PD-L1, mesothelioma cells can hide from immune cells and disguise themselves as healthy cells. 

Another way mesothelioma survives is by activating the CTLA-4 receptor on the surface of T cells, which “turns off” the ability of T cells to identify and destroy cancer cells. 

Examples of CTLA-4 inhibitor drugs include ipilimumab (Yervoy) and tremelimumab.

Nivolumab (Opdivo) and Ipilimumab (Yervoy)

Nivolumab benefits mesothelioma patients when given alone or combined with ipilimumab (Yervoy). Doctors can also prescribe this drug at any point in treatment, such as before or after chemotherapy or other medications. 

Patients with epithelioid type mesothelioma tend to benefit similarly from immunotherapy and chemotherapy. However, immunotherapy has shown to double the survival for patients with biphasic and sarcomatoid cell types.

The FDA approved the combination of Opdivo and Yervoy in 2020 as a first-line treatment for mesothelioma patients ineligible for surgery. The decision came after a pivotal clinical trial called Checkmate 743. 

Checkmate 743 included over 600 patients in a phase III trial who had never received treatment. Survival improved in the immunotherapy group by 26% compared to chemotherapy, a difference of about four months. However, immunotherapy side effects were more common by about 3%.

Pembrolizumab (Keytruda)

Pembrolizumab has a very similar mechanism to nivolumab and is FDA-approved as a second-line pleural mesothelioma treatment. The best candidates for this drug have received other medications but not immunotherapy in the past and have no other available treatment alternatives. 

Patients with a high tumor mutation burden, or a high mutation rate in mesothelioma tumor cells, benefit more from this medication. 

Immunotherapy Side Effects

Immunotherapy drugs heighten the immune system’s response. This mechanism can lead to inflammation or tissue damage in sensitive organs and symptoms similar to those during an infection. 

The most frequent side effect of immunotherapy drugs is inflammation. 

Monitoring side effects is vital and is usually done through blood tests before treatment. You must report any symptoms to your physician or clinical team while on immunotherapy. Side effects can happen any time and occur almost anywhere in the body. 

If you experience side effects during immunotherapy treatment, your doctor may stop the drug or lower the dose. You may also receive high doses of steroid medications with a slow taper or other targeted therapies depending on the organ affected and the severity. 

Promising New Treatments for Mesothelioma

Many potential therapies are currently in testing through clinical trials and offer an exciting glimpse into novel treatments available for mesothelioma patients. 

A combination of chemotherapy and immunotherapy together has shown benefits for mesothelioma patients in the clinical trials BEAT-meso, Dream3r and I227. 

Researchers are also exploring the effects of immunotherapy before surgery to improve the ability of surgeons to remove more tumor mass. Other trials are investigating radiation therapy for pain and symptom control. 

Tumor Treating Fields, or TTF, is a new therapy for mesothelioma patients in combination with platinum and pemetrexed chemotherapy. TTF is a wearable device that uses low-intensity alternating electric fields to interrupt dividing tumor cells and inhibit tumor growth.

The one-year survival for mesothelioma patients on TTF was 62.2%, and the two-year survival was 41.9%. More treatment centers are offering this new therapy as it becomes available. 

Cancer treatments are constantly evolving. Many new options are accessible to patients and even more promising therapies are on the horizon. Because mesothelioma is a rare type of cancer, seeing a mesothelioma specialist is the best way to access the latest treatments.