# The Evolving Role of Chemotherapy in the Management of Pleural Malignancies: Current Evidence and Future Directions

## TL;DR

This review discusses chemotherapy's role in treating pleural cancers, including recent advances and future research directions.

## Contribution

The paper provides an updated synthesis of chemotherapy strategies and highlights emerging intrapleural techniques for pleural malignancies.

## Key findings

- Platinum-based chemotherapy with pemetrexed is a standard treatment for mesothelioma.
- Intrapleural chemotherapy methods like hyperthermic intrathoracic chemotherapy are promising but require further study.
- Systemic therapy for metastatic pleural malignancies is tailored to the primary tumor's molecular profile.

## Abstract

Pleural malignancies, often resulting from metastatic cancers like lung or breast cancer, are aggressive and typically present with malignant pleural effusion, indicating advanced disease and poor prognosis. Malignant pleural mesothelioma, a rarer primary pleural cancer, is also associated with a severe clinical course. Treatment strategies include palliative care to relieve symptoms and improve quality of life, as well as definitive therapies such as systemic chemotherapy, targeted therapy, and immunotherapy. Standard treatments for mesothelioma involve platinum-based chemotherapy with pemetrexed and immunotherapy for unresectable cases. Systemic therapy for metastatic disease is based on the tumor’s origin and profile. Intrapleural chemotherapy, including hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy, represents a promising area under investigation. This review summarizes current therapeutic approaches, recent advances, and highlights gaps in knowledge to guide future research and clinical innovation.

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice.