The American Society of Clinical Oncology (ASCO) has released comprehensive updates to its pleural mesothelioma treatment guidelines, marking the first major revision since 2018. The new guidelines, based on analysis of 110 peer-reviewed studies from 2016-2024, introduce significant changes in surgical approaches, immunotherapy integration, and genetic testing protocols.
Refined Surgical Approach
The updated guidelines advocate for a more selective surgical strategy, moving away from widespread surgical intervention. This shift is supported by the phase 3 MARS-2 trial results, which demonstrated superior survival outcomes with chemotherapy alone (24.8 months median overall survival) compared to surgery followed by adjuvant chemotherapy (19.3 months). Surgical intervention is now recommended only for carefully selected patients with early-stage epithelioid disease, to be performed exclusively at high-volume specialized centers.
Immunotherapy Takes Center Stage
A major advancement in the guidelines is the establishment of immunotherapy as a cornerstone treatment. The combination of ipilimumab and nivolumab is now recommended as first-line therapy for non-epithelioid mesothelioma, following impressive results from the CheckMate 743 trial. The study showed significantly improved survival rates, with median overall survival reaching 18.1 months for immunotherapy compared to 8.8 months with chemotherapy in non-epithelioid cases.
Personalized Treatment Approaches
For patients with epithelioid mesothelioma, the guidelines outline multiple treatment options, including immunotherapy, traditional chemotherapy, or a novel chemoimmunotherapy combination of pembrolizumab with pemetrexed and platinum-based chemotherapy. Treatment selection should be individualized based on factors such as disease burden, comorbidities, and patient preferences.
Simplified Disease Classification
The guidelines introduce important changes in disease terminology, eliminating the term "malignant" from mesothelioma classification, as all mesotheliomas are now considered malignant by definition. The classification system maintains three primary subtypes: epithelioid, sarcomatoid, and biphasic, with subtype identification crucial for treatment planning.
Enhanced Role of Genetic Testing
A significant addition to the guidelines is the recommendation for universal genetic testing at diagnosis. This emphasis on genetic profiling, particularly for BAP1 gene mutations, reflects growing understanding of genetic factors in mesothelioma development and treatment response. Up to 14% of patients may carry relevant genetic mutations, making testing crucial for comprehensive care planning.
Treatment Selection Criteria
Dr. Hedy Lee Kindler, professor of medicine at The University of Chicago, emphasizes the importance of considering multiple factors in treatment selection. "When choosing between chemotherapy, doublet immunotherapy, or chemo-immunotherapy, key factors are histology, disease burden, comorbidities, and patient preference," she explains. The guidelines particularly note that patients with sarcomatoid or sarcomatoid-predominant biphasic disease should receive ipilimumab/nivolumab combination therapy unless contraindicated.
For epithelioid disease, treatment decisions require careful consideration of additional factors. Patients with high symptom burden or extensive disease may benefit most from chemoimmunotherapy, which shows a 62% response rate. Those with autoimmune conditions might be better suited for chemotherapy, while patients with reduced kidney function may need to pursue immunotherapy options.
These comprehensive updates represent a significant evolution in mesothelioma treatment, providing clinicians with clear, evidence-based guidance for optimizing patient care. The guidelines emphasize the importance of individualized treatment approaches and multidisciplinary care, marking a new era in the management of this challenging disease.
