bims-mesote 2025-01-19 papers

Issue of 2025–01–19
four papers selected by
Laura Mannarino, Humanitas Research

Respir Investig. 2025 Jan 15. pii: S2212-5345(25)00001-2. [Epub ahead of print]63(2): 200-209

Current drug therapy for pleural mesothelioma.

Pleural mesothelioma (PM) is a rare and highly aggressive malignancy originating from the pleural lining, with a median overall survival of merely 1 year. This cancer primarily arises from mesothelial cells following exposure to carcinogenic, biopersistent mineral fibers, particularly asbestos. The histological subtypes of mesothelioma are epithelioid (approximately 60%), sarcomatoid (20%), and biphasic (20%), exhibiting epithelioid and sarcomatoid characteristics. Classification is important for prognosis and guides the therapeutic strategy. Due to the typical late presentation, most patients with PM are ineligible for localized treatments such as surgery or radiotherapy. Systemic therapy, including cytotoxic chemotherapy, targeted therapies, and immunotherapy, is thus critical for managing advanced PM. For unresectable PM, decisions regarding systemic treatment are guided by patient suitability and histological characteristics. First-line therapies for advanced PM currently include the cisplatin-pemetrexed combination and the nivolumab-ipilimumab regimen. Historically, cisplatin-pemetrexed has been administered as first-line treatment, though recent advancements have introduced new therapies that significantly prolong patient survival. Innovative approaches combining immunotherapy and chemotherapy offer promising avenues for further improvement. Future treatment strategies should incorporate novel paradigms, such as combination chemo-immunotherapy, targeted agents, and potential cellular therapies, alongside companion biomarkers tailored to the histologic and molecular diversity of mesothelioma. This review explores the latest advancements in drug therapy for PM and provides an overview of current systemic treatment options.

Keywords: Chemotherapy; Immune checkpoint inhibitor; Mesothelioma; Systemic therapies; Target therapy

DOI: https://doi.org/10.1016/j.resinv.2024.12.017

Ann Oncol. 2025 Jan 13. pii: S0923-7534(25)00003-1. [Epub ahead of print]

A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab, as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13 18 BEAT-meso trial.

BACKGROUND: The currently approved frontline treatments for diffuse pleural mesothelioma (DPM) are ipilimumab-nivolumab or platinum-pemetrexed. The addition of bevacizumab to chemotherapy improves overall survival (OS). While single-agent immunotherapy or chemotherapy-immunotherapy combinations are superior to chemotherapy monotherapy, there is a potential for synergistic triple combination of chemotherapy, bevacizumab, and immunotherapy.
PATIENTS AND METHODS: BEAT-meso is an international open-label, 1:1 randomised phase III trial, with stratification factors histology and stage aiming to determine the efficacy and safety of adding atezolizumab (1200 mg, Q3W until progression) to bevacizumab (15 mg/kg, Q3W until progression) and standard chemotherapy (4-6 cycles of carboplatin AUC5 with pemetrexed 500 mg/m2, Q3W; ABC versus BC) as first-line treatment for advanced DPM. The primary endpoint is OS in all randomised patients, aiming to a relative benefit of 29% (HR=0.708). Secondary endpoints include progression-free survival (PFS), adverse events (AEs) and symptom-specific and global quality of life (QoL).
RESULTS: Between 30/04/2019 and 7/03/2022, 400 patients were randomised, 200 per arm. 65% had ECOG performance status 1 and 78% had epithelioid histology. At a median follow-up of 35 months (data cut-off 1/09/2023), the median OS was 20.5 months for ABC versus 18.1 months for BC (HR(95%CI): 0.84(0.66-1.06); p=0.14). Median PFS was significantly longer for ABC than BC (9.2 vs 7.6 months); HR: 0.72(0.59-0.89); p=0.0021). Histology showed significant treatment interaction for both PFS and OS, with OS HR: 0.51(0.32-0.80) for non-epithelioid and 1.01(0.77-1.32) for epithelioid (interaction p=0.012). Grade≥3 treatment-related AEs were reported in 55% of patients in ABC and 47% in BC, QoL was maintained with ABC with no clinically meaningful differences from BC.
CONCLUSIONS: The significant benefit in median PFS for ABC found in this study translated into a numerical but not significant increase in median OS. Thus, the primary endpoint was not met. In the pre-specified analysis by histology, superior OS and PFS were found for ABC in non-epithelioid cases.

Keywords: Mesothelioma; bevacizumab; chemotherapy; immunotherapy; pleural

DOI: https://doi.org/10.1016/j.annonc.2024.12.014

Ann Surg. 2025 Jan 15.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

Juuso Paajanen, William G Richards, Yue Xie, Emanuele Mazzola, Kristina Sidopoulos, John Kuckelman, Ritu R Gill, Raphael Bueno.

OBJECTIVE: We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS).
SUMMARY BACKGROUND DATA: Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery.
METHODS: All patients who underwent PD between 1998 and 2022 were identified. Patients with diffuse PM who achieved macroscopic complete resection and had sufficient information on tumor relapse were included. Postoperative scans were reviewed to determine the timing and sites of the first recurrence.
RESULTS: A total of 436 patients had tumor recurrence during follow-up. Local recurrences occurred most frequently (N=370, 85%) and represented the only recurrence site in 29% (N=129) of cases. Patients with sarcomatoid tumors relapsed earlier than other subtypes (P=0.003) with more frequent distant spread compared to other subtypes (P<0.001). Multivariable analysis revealed that age (P=0.015), preoperative tumor volume (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), and TNM stage IV (P=0.003) were associated with DFI. Similarly, age (P=0.042), performance status (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), TNM stages III and IV (P=0.003 and 0.010 respectively), type of surgery (P=0.019), and number of recurrent lesions (P=0.024) were associated with PRS. Recurrence surgery (HR 0.46, 95% CI 0.29-0.74) and chemotherapy (HR 0.69, 95% CI 0.54-0.92) were independently associated with PRS in patients with distant with or without local recurrences.
CONCLUSIONS: PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases.

DOI: https://doi.org/10.1097/SLA.0000000000006627

JTO Clin Res Rep. 2025 Jan;6(1): 100756

Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1-Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study.

Prashasti Agrawal, Michael Offin, Victoria Lai, Michelle S Ginsberg, Prasad S Adusumilli, Valerie W Rusch, Jennifer L Sauter, Teresa Ho, Phillip Wong, Marjorie G Zauderer.

Introduction: WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non-human leukocyte antigen-restricted, heteroclitic WT1-specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival.
Methods: To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity.
Results: Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months.
Conclusions: Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size.

Keywords: Cancer vaccines; Immunotherapy; Mesothelioma; Phase 1

DOI: https://doi.org/10.1016/j.jtocrr.2024.100756