Neoadjuvant atezolizumab combination meets safety criteria in pleural mesothelioma

Neoadjuvant cisplatin and pemetrexed plus atezolizumab followed by surgical resection and maintenance atezolizumab has met safety criteria, according to research presented at the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer. 

Dr Anne Tsao of MD Anderson Cancer Center in Houston, US, and her clinical site co-researchers randomly assigned 24 patients with epithelioid or biphasic histology whose disease was resectable by pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP), who underwent extended surgical staging with mediastinoscopy or endobronchial ultrasound and laparoscopy, and who did not receive prior chemotherapy or immunotherapy. 

Safety was defined as no Grade 4-5 immune-related adverse event; feasible if 75 percent received at least one dose of maintenance therapy. Patients were divided into two cohorts: the P/D cohort or the EPP cohort.  Patients received four cycles of neoadjuvant cisplatin and pemetrexed plus atezolizumab (CPA), resection, then radiation (EPP cases only), followed by one year of maintenance atezolizumab.  

Twenty-eight eligible patients were enrolled and 25 received at least two cycles of neoadjuvant CPA. Eighteen underwent surgery and 15 received maintenance atezolizumab. Median age was 68.1, with 20 men and eight women. There were 24 planned P/D and four planned EPPs. Twenty-one patients completed neoadjuvant therapy, however seven patients did not proceed to resection (two toxicity, four disease progression and one death). The one treatment-related death occurred from sepsis associated with non-immune-related renal and respiratory failure.

Eighteen patients with stable disease or partial response proceeded to surgical resection; 17 received a P/D and one EPP. One patient did not receive protocol-specified surgery due to progressive disease. Postoperatively, one patient had a fatal cardiovascular event. Sixteen patients registered to receive maintenance atezolizumab for one year, but one patient was ineligible due to inadequate haematologic function.  

To date, no treatment-related adverse events more serious than Grade 3 were reported and three patients remain ongoing with maintenance atezolizumab therapy.  

“Neoadjuvant cisplatin and pemetrexed plus atezolizumab followed by surgical resection and maintenance atezolizumab met safety criteria,” Dr Tsao summarised. “Sixty percent of eligible patients proceeded to maintenance atezolizumab, and additional monitoring will assess efficacy and long-term toxicity outcomes.”