Atezolizumab regimen safe for resectable mesothelioma
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Use of atezolizumab as part of neoadjuvant therapy and again as maintenance met predetermined safety criteria for patients with resectable pleural mesothelioma, according to study results.
No grade 4 or higher treatment-related adverse events occurred, researchers reported at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
The regimen also demonstrated a preliminary efficacy signal, Boris Sepesi, MD, associate professor in the department of thoracic and cardiovascular surgery at The University of Texas MD Anderson Cancer Center, said during a presentation.
“This trial highlights the challenging nature of neoadjuvant therapy trials in this patient population, because of the heterogeneity of the disease and how patients react, as well as the complex and difficult surgical therapy,” Sepesi said. “However, I think this is a step forward in terms of treatment.”
Treatment options are limited for malignant pleural mesothelioma. Median OS ranges from 17 months to 25 months for patients who undergo neoadjuvant chemotherapy, surgical resection and adjuvant radiation.
A prior study reported PD-L1 expression among 40% of patients with malignant pleural mesothelioma. That study identified PD-L1 expression as a negative biomarker for disease burden and survival (6 months with PD-L1 expression vs. 14 months without; P < .0001), according to study background.
Sepesi and colleagues hypothesized that adding the anti-PD-L1 inhibitor atezolizumab (Genentech, Roche) to neoadjuvant therapy with cisplatin and pemetrexed, followed by maintenance atezolizumab, may enhance T-cell activation against microscopic disease and extend survival.
Researchers evaluated 28 eligible patients (median age, 68.1 years; range, 31.4-77.3; men, n = 20; white, n = 24) with resectable mesothelioma who had not received prior chemotherapy or immunotherapy.
Neoadjuvant treatment consisted of four cycles of cisplatin (75 mg/m2) and pemetrexed (500 mg/m2) plus 1,200 mg atezolizumab via IV every 3 weeks.
Patients who did not experience disease progression then underwent by resection by pleurectomy/decortication or extrapleural pneumonectomy (EPP). Those who underwent EPP received radiation.
Patients subsequently received 1 year of maintenance atezolizumab dosed at 1,200 mg via IV every 3 weeks.
Twenty-five patients received at least two cycles of cisplatin, pemetrexed and atezolizumab and 21 patients completed neoadjuvant therapy.
Eighteen patients who achieved partial response or stable disease after neoadjuvant treatment proceeded to surgical resection. All but one underwent pleurectomy/decortication. One patient experienced a fatal cardiovascular event after surgery.
Fifteen patients received atezolizumab maintenance.
The study met the established safety criteria of no grade 4 or grade 5 immune-related adverse events. No treatment-related adverse events more serious than grade 3 occurred.
The most common adverse events reported during the neoadjuvant therapy phase included nausea (grade 1, n = 9; grade 2, n = 10; grade 3, n = 1), fatigue (grade 1, n = 10; grade 2, n = 5), anemia (grade 1, n = 5; grade 2, n = 5; grade 3, n = 2), anorexia (grade 1, n = 7; grade 2, n = 4) and neutropenia (grade 1, n = 4; grade 2, n = 4; grade 3, n = 3).
One patient experienced grade 4 acute renal injury and grade 5 sepsis deemed unrelated to treatment.
The most common adverse events reported during the maintenance therapy phase included fatigue (grade 1, n = 5; grade 2, n = 1), anorexia (grade 1, n = 2; grade 2, n = 1), nausea (grade 1, n = 2; grade 2, n = 1), constipation (grade 1, n = 2), creatinine increase (grade 1, n = 1; grade 2, n = 1) and hypothyroidism (grade 1, n = 1; grade 2, n = 1). Researchers reported one grade 3 event — a case of hypotension — in this phase.
Researchers observed no new safety signals in the neoadjuvant or maintenance phases.
At data cutoff, three patients were continuing atezolizumab maintenance.
Median PFS was 18.6 months (95% CI, 14.2-30.1). Median OS had not been reached (95% CI, 18.4-not reached).
“Some of these results are comparable to or perhaps slightly better than those of historical cohorts, but we will have to complete the trial and complete the adequate follow-up to be able to make any conclusions,” Sepesi said.
Perspective
Back to TopShani Shilo, DMD, PhD
Mesothelioma is a very aggressive disease and, although case numbers are decreasing around the world, it remains a tremendous unmet need.
It is very encouraging to see that this regimen did not cause adverse events greater than grade 3. Lung cancer treatment has improved with the development of targeted therapies, but we need to look beyond the concept of elongated life and continue to address the question of quality of life. From that standpoint, this is a very good result.
We need more research and more clinical trials in mesothelioma. We also need to encourage and empower more people with mesothelioma and their caregivers to rise up and become advocates.
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Tsao A, et al. Abstract OA13.01. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer (virtual meeting); Sept. 8-14, 2021.
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