Guidelines for Mesothelioma Now Offer More Treatment Options

For nearly 20 years, mesothelioma treatment options were limited to a single regimen: pemetrexed with a platinum agent. Now, there are 3 systemic treatment options available. In this video, Hedy Lee Kindler, MD, explains these new advancements:

Chemotherapy: Pemetrexed with cisplatin or carboplatin, with or without bevacizumab (Avastin).

Immunotherapy: A combination of ipilimumab (Yervoy) and nivolumab (Opdivo).

Chemoimmunotherapy: Pemetrexed, carboplatin, and pembrolizumab (Keytruda).

Kindler also discusses how to determine the best treatment approach based on a patient’s specific condition, including histology, renal function, autoimmune disease, and genetic factors such as BAP1 mutations.

Investigators identified and reviewed trials published between 2016 and 2024. A trial that led to a key approval in the guideline was the phase 3 CheckMate 743 trial (NCT02899299), which evaluated nivolumab plus ipilimumab vs chemotherapy alone in patients with non-epithelioid tumors. The phase 3 MARS-2 trial (NCT02040272) that evaluated chemotherapy alone vs surgery followed by adjuvant chemotherapy provided data for guideline investigators to suggest a more limited role of surgery for mesothelioma.For more details on the trial data that influenced this guideline update, read our article here.

There are 2 ongoing studies (NCT03830229; NCT04431024) evaluating patients with mesothelioma as well as their families with a BAP1 gene variant to better understand the disease and the link to other cancers. Investigators are using imaging, clinical screenings, and minimally invasive procedures to track its progression and identify risk factors. These trials are actively accruing and may provide further insight into the genetic factors associated with mesothelioma.

Kindler is a professor of medicine in the section of hematology/oncology and associate dean for clinical science research and human subjects at The University of Chicago, Biological Sciences Division.

Transcription

00:13 | For almost 20 years, we only had 1 treatment, pemetrexed with a platinum agent. Now we have 3 key systemic therapies: We have pemetrexed with cisplatin or carboplatin with or without bevacizumab. We have doublet immunotherapy with ipilimumab and nivolumab, and we have chemoimmunotherapy with pemetrexed, carboplatin and pembrolizumab.

00:39 | Some of the usual aspects take place. [If] someone has impaired renal function, you are not going to give them pemetrexed. [If] someone has severe autoimmune disease, you are not going to give them immunotherapy.

00:53 | Outside of that, “how do you choose which regimen is right for which patient?” The differences between the regimens in terms of histology are important, and so [a patient] can no longer simply have malignant mesothelioma not otherwise specified. You need to identify [if the patient has] pure epithelioid, in which case chemotherapy or chemoimmunotherapy are best. Does [the patient] have pure sarcomatoid or biphasic [mesothelioma] in which case, a double in immunotherapy is likely best.

1:25 | Do you have a patient where you want to get a high response rate, for example, in the neoadjuvant setting, [where a patient has] a large volume of disease? You are going to get almost double the response rate with chemoimmunotherapy compared with chemotherapy or immunotherapy [alone]. [In this case] you want to use a chemoimmunotherapy. Finally, for a patient with a germline mutation, particularly a BAP1 germline mutation. Those are patients who will benefit from having platinum contained in the regimen.