This protocol covers a specific and clinically important presentation: patients newly diagnosed with pleural mesothelioma whose tumour has nonepithelioid histology and who have a medical contraindication to immunotherapy, with no prior systemic therapy received.

Clinical Scenario

Nonepithelioid histology Immunotherapy contraindicated Treatment-naive

The nonepithelioid histologic subtype represents a distinct biological and clinical category within pleural mesothelioma. When immunotherapy cannot be used due to a medical contraindication, the treatment pathway diverges from standard first-line approaches that incorporate immune checkpoint agents.

For treatment-naive patients in this situation, evidence-based systemic options exist that are specifically evaluated in this population.

Treatment Approach — Partial Overview

The protocol identifies specific systemic therapy regimens appropriate for this scenario. Combination chemotherapy strategies — including options developed for patients who cannot receive immunotherapy — are central to the approach. The full selection criteria, agent combinations, and clinical algorithm are available in the complete protocol.

References

DOI: 10.1200/JCO-24-02425

In patients with nonepithelioid histology who have not received any prior systemic therapy and are not candidates for immunotherapy, the addition of pegargiminase to pemetrexed plus platinum chemotherapy may be offered as a treatment option.

Gemcitabine with ramucirumab may be offered to patients with disease progression after treatment with platinum pemetrexed chemotherapy.

Oral vinorelbine may be offered to patients with disease progression after treatment with platinum pemetrexed chemotherapy.

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Treatment of Newly Diagnosed Pleural Mesothelioma — Nonepithelioid Subtype with Medical Contraindication to Immunotherapy

Clinical Scenario

Treatment Approach — Partial Overview

References