No new safety signals for neoadjuvant, maintenance atezolizumab in mesothelioma
medwireNews: Neoadjuvant atezolizumab meets researcher-defined safety criteria for use in combination with cisplatin plus pemetrexed and then as postsurgical maintenance therapy for people with resectable malignant pleural mesothelioma.
The “highly stringent criteria” set out by Anne Tsao (The University of Texas MD Anderson Cancer Center, Houston, USA) and colleagues meant that none of the 25 patients who received at least two cycles of the regimen experienced a grade 4 or 5 immune-related adverse event (AE).
Tsao presented the findings of the safety and feasibility trial at the IASLC 2021 World Conference on Lung Cancer.
She explained that 25 of 28 enrolled patients with stage I–III malignant pleural mesothelioma received at least two cycles of neoadjuvant atezolizumab 1200 mg plus cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks, and 21 completed four cycles. Reasons for not completing neoadjuvant therapy included disease progression (n=4), toxicity (n=2), and death due to sepsis associated with grade 4 non-immune-related renal and respiratory failure (n=1).
Eighteen (64.2%) patients with a partial response or stable disease then proceeded to surgical resection with pleurectomy/decortication (n=17) or extrapleural pneumonectomy (n=1). Tsao noted that one patient did not receive protocol-specified surgery due to progressive disease with chest wall invasion and one patient experienced a fatal, postoperative cardiovascular event.
Of the patients that underwent surgery, 15 received atezolizumab maintenance for up to 1 year and at the time of the presentation, one patient was still on this treatment. However, at 60.0% of those enrolled, the proportion who received at least one dose of maintenance therapy fell short of the predefined cutoff of 75% that the researchers required for feasibility.
During a median 10.3 months of follow-up, there were no immune-related AEs above grade 3 reported, and the majority of events were grade 1 or 2 in severity with “no new safety signals” for either the neoadjuvant or maintenance regimens, said Tsao.
The most common grade 3 treatment-related AEs during the neoadjuvant phase were neutropenia (n=3) and anemia (n=2). There was one case each of diarrhea, febrile neutropenia, hyponatremia, nausea, and vomiting. During the maintenance phase one patient experienced grade 3 hypotension but there no other grade 3 or worse AEs.
At the time of the analysis, median overall survival had not been reached and median progression-free survival was 18.6 months.
Tsao concluded that the “trial highlights the challenging nature of neoadjuvant therapy trials in this patient population.”
She added: “We need to conduct more research with window of opportunity studies to identify the biomarkers that are predictive of benefit to these different treatments that we give our patients.”
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