Alvise Berti1, Roberto Bortolotti2, Mariachiara Dipasquale3, Stefania Kinspergher4, Larry Prokop5, Guido Grandi6, Sandro Inchiostro7, Giuseppe Paolazzi8, Orazio Caffo9, Antonello Veccia10. 1. Department of Immunolgy and Rheumatology, Santa Chiara Hospital, Trento, Italy; Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN, USA. Electronic address: alvise.berti@apss.tn.it. 2. Department of Immunolgy and Rheumatology, Santa Chiara Hospital, Trento, Italy. Electronic address: roberto.bortolotti@apss.tn.it. 3. Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address: mariachiara.dipasquale@apss.tn.it. 4. Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address: stefania.kinspergher@apss.tn.it. 5. Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA. Electronic address: prokop.larry@mayp.edu. 6. Department of CIBIO, University of Trento, Italy. Electronic address: guido.grandi@unitn.it. 7. Internal Medicine, San Lorenzo Hospital, Borgo Valsugana, Italy. Electronic address: sandro.inchiostro@apss.tn.it. 8. Internal Medicine, San Lorenzo Hospital, Borgo Valsugana, Italy; Department of Rheumatology, San Camillo Hospital, Trento, Italy. Electronic address: paolazzigiuseppe@gmail.com. 9. Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address: orazio.caffo@apss.tn.it. 10. Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address: antonello.veccia@apss.tn.it.
Abstract
INTRODUCTION: The introduction in clinical practice of the immune checkpoint inhibitors (ICIs) radically changed the treatment algorithm of lung cancers. To characterize the toxicity of ICIs (atezolizumab, durvalumab, nivolumab, pembrolizumab) is important for personalizing treatment. PATIENTS AND METHODS: We performed a systematic review and meta-analysis of phase III randomized controlled trials assessing ICIs, from inception until April 23rd, 2020. We extracted the data from the ICI arm of each trial for indirect comparisons to estimate relative risk for immune-related adverse events (irAEs), severe (grade ≥3) irAEs, drug discontinuation due to irAEs or toxic death. RESULTS: Sixteen trials included a total of 6226 subjects randomized to the experimental immunotherapy arm. Immunotherapy was administered in monotherapy (8 trials), in combination with chemotherapy (6 trials) or other ICI (2 trials). Any grade irAEs and severe irAEs for ICI were 37.1% and 18.5%, respectively. Discontinuations due to any grade irAEs and severe irAEs were 13.8% and 9.2%, respectively; toxic deaths were 2.9% in the immunotherapy arm. Pooled data on any, severe and organ-specific irAEs showed that immunotherapy has a significantly lower risk of irAEs compared to immuno-chemotherapy, especially when analysis was restricted to monoimmunotherapy, like drug discontinuation and toxic death (all p < 0.05). Detailed comparisons between different ICIs provided treatment-related risk profiles for organ-specific irAEs. CONCLUSIONS: Our findings contribute to clarifying frequency and features of immune-related toxicities between different ICIs in lung cancer patients, including any grade irAEs, severe irAEs, drug discontinuation and toxic deaths, and may be useful to inform the selection of treatment.
INTRODUCTION: The introduction in clinical practice of the immune checkpoint inhibitors (ICIs) radically changed the treatment algorithm of lung cancers. To characterize the toxicity of ICIs (atezolizumab, durvalumab, nivolumab, pembrolizumab) is important for personalizing treatment. PATIENTS AND METHODS: We performed a systematic review and meta-analysis of phase III randomized controlled trials assessing ICIs, from inception until April 23rd, 2020. We extracted the data from the ICI arm of each trial for indirect comparisons to estimate relative risk for immune-related adverse events (irAEs), severe (grade ≥3) irAEs, drug discontinuation due to irAEs or toxic death. RESULTS: Sixteen trials included a total of 6226 subjects randomized to the experimental immunotherapy arm. Immunotherapy was administered in monotherapy (8 trials), in combination with chemotherapy (6 trials) or other ICI (2 trials). Any grade irAEs and severe irAEs for ICI were 37.1% and 18.5%, respectively. Discontinuations due to any grade irAEs and severe irAEs were 13.8% and 9.2%, respectively; toxic deaths were 2.9% in the immunotherapy arm. Pooled data on any, severe and organ-specific irAEs showed that immunotherapy has a significantly lower risk of irAEs compared to immuno-chemotherapy, especially when analysis was restricted to monoimmunotherapy, like drug discontinuation and toxic death (all p < 0.05). Detailed comparisons between different ICIs provided treatment-related risk profiles for organ-specific irAEs. CONCLUSIONS: Our findings contribute to clarifying frequency and features of immune-related toxicities between different ICIs in lung cancerpatients, including any grade irAEs, severe irAEs, drug discontinuation and toxic deaths, and may be useful to inform the selection of treatment.
Authors: Juan Jiang; Yuling Wang; Yang Gao; Haruhiko Sugimura; Fabrizio Minervini; Junji Uchino; Balazs Halmos; Sai Yendamuri; Jeffrey B Velotta; Min Li Journal: Transl Lung Cancer Res Date: 2022-02