Mesothelioma is a cancer that affects the lining of the organs, most commonly the pleural lining of the lungs. A family history of mesothelioma and exposure to asbestos increase the risk of developing this type of cancer. Symptoms may include shortness of breath, chest pain, fatigue, cough, fever, and unexplained weight loss. Most patients undergo a combination of treatments — surgery, chemotherapy, radiation, targeted therapy, and/or immunotherapy.
In this side-by-side comparison, we look at the latest clinical practice guidelines from the American Society of Clinical Oncology (ASCO) and the Society for Immunotherapy of Cancer (SITC) on immunotherapy for mesothelioma. We encourage you to review the full guidelines which can be found at the links below.
Guidelines for Comparison
| Item | Treatment of Pleural Mesothelioma: ASCO Guideline Update | Addendum 1: Society for Immunotherapy of Cancer (SITC) Clinical Practice Guideline on Immunotherapy for the Treatment of Lung Cancer and Mesothelioma |
|---|---|---|
| Authoring Organization | American Society of Clinical Oncology | Society for Immunotherapy of Cancer |
| Publication Date | January 2025 | July 2025 |
| Graded Recommendation | Yes | Yes |
| Uses GRADE | Yes | No, uses Oxford levels of evidence |
| Links | Summary / Full Text | Summary / Full Text |
Key Takeaways
Now we will review the similarities and differences in immunotherapy treatment recommendations for mesothelioma between ASCO and SITC.
Testing to guide chemotherapy and/or immunotherapy agent selection:
- Both societies recommend against programmed death-ligand 1(PD-L1) testing because of the benefit of nivolumab plus ipilimumab regardless of PD-L1 expression.
- ASCO also recommends against tumor mutation burden (TMB) and microsatellite instability (MSI) testing to determine the choice of chemotherapy or immunotherapy.
First-Line Immunotherapy:
- Nivolumab plus ipilimumab
- Both societies agree that nivolumab plus ipilimumab should be offered as first-line treatment for epithelioid mesothelioma and are strongly recommended for non-epithelioid mesothelioma.
- ASCO recommends that nivolumab and ipilimumab be administered for 2 years duration in patients without disease progression or intolerability. SITC did not address the duration of treatment in this update.
- Pembrolizumab with pemetrexed and platinum-based chemotherapy
- ASCO recommends offering this combination as a first-line treatment option for patients newly diagnosed with either epithelioid or nonepithelioid mesothelioma.
- SITC considers this combination as a first-line treatment option for patients with metastatic malignant pleural mesothelioma.
Second-Line/Subsequent-Line Therapy:
- ASCO recommended second-line treatment with double- or single-agent immunotherapy for patients previously treated with chemotherapy.
- SITC on the other hand recommends offering platinum-based chemotherapy with pemetrexed for patients with progression following nivolumab and ipilimumab and enrollment in a clinical trial as a third-line for patients with progression following treatment with all three of the above agents.
- ASCO recommends offering retreatment with immunotherapy for patients with initial disease control who had progression after immunotherapy was stopped. SITC did not address retreatment.
Management of immune checkpoint inhibitor (ICI) toxicities:
- ASCO recommends that patients with severe immunotherapy-related toxicities discontinue immunotherapy.
- SITC recognizes that immune checkpoint inhibitors are associated with distinct toxicities compared with conventional cancer treatments, known as, immune-related adverse events (irAEs). They recommend monitoring and treatment for such toxicities at specialized treatment centers.
- SITC also recommends monitoring for and treatment of immune-related toxicities for patients receiving tarlatamab.
Comparisons of Recommendations
| Type | ASCO | SITC |
|---|---|---|
| Treatment Choice | PD-L1, TMB, or MSI should not be used to determine choice of chemotherapy or immunotherapy in patients with pleural mesothelioma. | For patients with mesothelioma, routine PD-L1 testing is not recommended, as benefit from immunotherapy with nivolumab plus ipilimumab was seen regardless of PD-L1 expression. |
| First-Line Therapy: Ipilimumab Plus Nivolumab | In patients with newly diagnosed pleural mesothelioma, ipilimumab plus nivolumab immunotherapy should be offered as a first-line systemic treatment option. In patients with newly diagnosed epithelioid mesothelioma, ipilimumab plus nivolumab immunotherapy should be offered as a first-line systemic treatment option. In patients with newly diagnosed nonepithelioid mesothelioma, ipilimumab plus nivolumab immunotherapy should be offered as the recommended first-line treatment. Ipilimumab plus nivolumab immunotherapy should be administered for a duration up to 2 years in the absence of disease progression or intolerable toxicity. | For patients with epithelioid subtype mesothelioma, treatment with nivolumab plus ipilimumab may be considered based on comparable outcomes to SOC chemotherapy. However, treatment decisions should be individualized and take into account the differing side effect profiles of combination immunotherapy and chemotherapy. For patients with non-epithelioid subtype mesothelioma, treatment with nivolumab plus ipilimumab is strongly recommended based on an almost twofold increase in median OS compared with SOC chemotherapy. |
| First-Line Therapy: pembrolizumab with pemetrexed and platinum-based chemotherapy | In patients with newly diagnosed pleural mesothelioma (epithelioid or nonepithelioid), chemoimmunotherapy with pembrolizumab and pemetrexed plus platinum-based chemotherapy may be offered as a first-line systemic treatment option. | For patients with metastatic malignant pleural mesothelioma, pembrolizumab with pemetrexed and platinum-based chemotherapy as first-line treatment may be considered. |
| Second-Line Therapy | In patients previously treated with chemotherapy, double-agent immunotherapy may be offered as a treatment option. In patients previously treated with chemotherapy, single-agent immunotherapy may be offered as a treatment option. | For patients with mesothelioma that has progressed following front-line treatment with nivolumab and ipilimumab, platinum-based chemotherapy with pemetrexed should be considered. Patients with mesothelioma that have progressed following immunotherapy and pemetrexed with platinum-based chemotherapy should be encouraged to enroll in clinical trials. |
| Pretreatment with Immunotherapy | Retreatment with immunotherapy may be offered to patients with initial disease control on immunotherapy whose disease subsequently progressed after completing treatment. | Not addressed. |
| ICI Toxicities (irAEs) | Patients with severe immunotherapy-related toxicities should discontinue immunotherapy since this does not impair long-term benefit. | Patients receiving tarlatamab should be monitored for and treated for cytokine release syndrome (CRS) and other immune-related toxicities. These toxicities can be severe, and when appropriate, referral or consultation with a specialized treatment center is recommended. |
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