Assessing the Addition of IMPRINT to Surgery and Systemic Therapy for Malignant Pleural Mesothelioma (NRG-LU006)

November 09 2022

The NRG-LU006 Phase III clinical trial compares adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) combined with pleurectomy/decortication (P/D) surgery and systemic therapy to surgery and systemic therapy alone for patients with malignant pleural mesothelioma (MPM). The goal of this study is to see if the addition of adjuvant hemithoracic IMPRINT can improve overall survival for this patient population.

One of the prevalent issues with MPM populations is poor local disease control. Previously, extrapleural pneumonectomy (EPP) was utilized as the standard surgical procedure for patients with MPM; however, the risk of locoregional recurrences remained high despite the extensive surgery. The addition of conventional hemithoracic radiation therapy to EPP reduced locoregional recurrences, but EPP +/- hemithoracic radiation therapy was also associated with significant morbidity and mortality risks. Practice shifted to using P/D as the preferred lung-sparing surgical approach for patients with MPM, but P/D typically results in a less complete resection and is associated with high rates of local failures in the chest. This opened the pathway to combining P/D with systemic therapy and radiation therapy to potentially improve locoregional recurrences and survival outcomes with less associated risks.

Patients with pathologically confirmed, clinical stage I-IIIA MPM amenable to macroscopic complete resection are eligible for NRG-LU006. If the patient received neoadjuvant systemic therapy before study entry, they have surgery once enrolled, and if the patient did not receive neoadjuvant systemic therapy, they have the P/D procedure within 4 weeks of study entry followed by pemetrexed and cisplatin (or carboplatin) 4 to 8 weeks after surgery.

Following this treatment, patients are stratified by type of systemic therapy (chemotherapy or immunotherapy with or without chemotherapy), mesothelioma subtype, and macroscopic complete resection. Patients will then be randomly assigned to one of two potential treatment arms. Treatment Arm 1 will receive no adjuvant radiotherapy whereas Treatment Arm 2 will receive adjuvant hemithoracic IMPRINT.

In addition to improving overall survival, NRG-LU006 aims to determine and compare local failure-free survival, distant-metastasis-free survival, progression-free survival, treatment-related toxicities, and clinically meaningful 10-point change in global health status mean scores between treatment arms at 9 months after randomization. NRG-LU006 also has several exploratory objectives listed in the protocol.

“Should NRG-LU006 successfully result in overall survival benefit from the use of IMPRINT, this trial would establish the multimodality approach of P/D, systemic therapy, and adjuvant hemithoracic pleural IMRT as a new standard treatment paradigm for resectable MPM,” stated Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center and the Principal Investigator of the NRG-LU006 trial.

Learn more about this trial at

Protocol documents and materials are located on the CTSU website

NRG-LU006 has a patient-facing study webpage available as well on the NRG website at

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