Neoadjuvant systemic therapy for pleural mesothelioma patients: a systematic review

Pleural mesothelioma is an aggressive malignancy with a poor prognosis. The role of surgery in its management remains controversial, with ongoing debate regarding the definition of resectable disease. Neoadjuvant therapy aims to reduce tumor burden. This systematic review evaluates prospective neoadjuvant trials in pleural mesothelioma to identify subgroups that may benefit from this approach.

A systematic search was conducted from inception to July 01, 2024, for phase II/III prospective trials evaluating neoadjuvant systemic therapy followed by surgery in adult patients with histologically confirmed pleural mesothelioma. Data were extracted on patient characteristics, treatment regimens, surgical outcomes, survival, and adverse events.

Sixteen trials were found: 861/1,184 patients (72.7%) were male, median age ranged between 57-69 years. Neoadjuvant chemotherapy was used in 15 trials and immunotherapy in one trial. Surgery was performed in 61.8% of patients, with extrapleural pneumonectomy (EPP) being the predominant approach. Median overall survival in single-arm trials was 17.4 months [95% confidence interval (CI): 15.8-19.0], n=523 for the intention-to-treat population and 21.4 months (95% CI: 19.2-23.7), n=345 for the surgery population. The phase III trial (MARS-2) comparing neoadjuvant chemotherapy plus extended pleurectomy decortication versus chemotherapy alone found a shorter median survival in the surgery and chemotherapy group {19.3 months [interquartile range (IQR), 10.0-33.7 months] vs. 24.8 months (IQR, 12.6-37.4 months), P=0.01}.

This review shows that the predominant neoadjuvant approach consists of platinum doublet chemotherapy, but the role of immunotherapy is being explored. Additional randomized trials are needed to determine the optimal neoadjuvant strategy and patient subgroups most likely to benefit.