Syed Hussaini1, Rania Chehade2, Ronald Gabriel Boldt3, Jacques Raphael4, Phillip Blanchette5, Saman Maleki Vareki6, Ricardo Fernandes7. 1. Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Syed.hussaini@lhsc.on.ca. 2. Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Rania.chehade@lhsc.on.ca. 3. Division of Experimental Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Gabriel.boldt@lhsc.on.ca. 4. Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Jacques.raphael@lhsc.on.ca. 5. Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada. Electronic address: Phillip.blanchette@lhsc.on.ca. 6. Division of Experimental Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada. Electronic address: Saman.malekiVareki@lhsc.on.ca. 7. Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada. Electronic address: Ricardo.fernandes@lhsc.on.ca.
Abstract
BACKGROUND: The use of immune checkpoint inhibitors (ICIs) has become standard therapy in many tumor sites. The aim of this study is to systematically review the literature to determine whether the incidence of immune-related adverse events (irAEs) after the use of ICIs is associated with clinical outcomes in all solid malignancies. METHODS: Embase and PubMed were searched from January 1st, 2000 until March 14, 2020 for relevant studies assessing the relationship between irAEs and treatment efficacy. Outcome measures of interest included: incidence of irAEs, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Of 3384 unique citations, 51 studies met inclusion criteria. Studies included melanoma (n = 21), lung (n = 19), renal (n = 4), urothelial (n = 1), head and neck (n = 2) and gastrointestinal cancers (n = 1). In patients with metastatic melanoma (n = 1474), the development of irAEs (irAE + versus irAE-) was associated with better weighted average OS (15.24 months (95% CI 9.95 to 20.5) versus 8.94 months (95% CI 7.76 to 10.1), HR = 0.46 (n = 640, CI 0.35-0.62, p < 0.00001), PFS (17.61 months (95% CI 10.1 to 25.1) versus 2.23 months (95% CI 1.77 to 2.68), HR = 0.51 (n = 1763, CI 0.42-0.63, p < 0.00001), and ORR (37.67% (95% CI 32.8 to 42.5) versus. 23.44% (95% CI 17.8 to 29.1). Similarly, in lung cancer patients, the ORR (irAE + versus. irAE-) was 41.49% (95% CI 36.5 to 46.5) versus 18.01% (95% CI 13.5 to 22.6). The weighted average PFS and OS were 8.97 months (95% CI 7.14 to 10.8) versus 3.06 months (95% CI 2.4 to 3.72) with HR = 0.46 (n = 1575, CI 0.39-0.54, p < 0.00001) and 19.07 months (95% CI 14.3 to 23.8) versus 7.45 months (95% CI 5.34 to 9.56) HR = 0.40 (n = 1085, CI 0.30-0.51, p < 0.00001), respectively. Improved treatment efficacy in patients who developed irAEs was also seen in renal cell carcinoma, urothelial and head and neck cancers. Notably, grade 3 or 4 irAEs were associated with increased ORR but worse OS. CONCLUSION: A positive association was noted between the development of irAEs and ORR, PFS, and OS in patients treated with ICIs, irrespective of disease site, type of ICI and irAE. Grade 3 or higher toxicities resulted in better ORR, but worse OS.
BACKGROUND: The use of immune checkpoint inhibitors (ICIs) has become standard therapy in many tumor sites. The aim of this study is to systematically review the literature to determine whether the incidence of immune-related adverse events (irAEs) after the use of ICIs is associated with clinical outcomes in all solid malignancies. METHODS: Embase and PubMed were searched from January 1st, 2000 until March 14, 2020 for relevant studies assessing the relationship between irAEs and treatment efficacy. Outcome measures of interest included: incidence of irAEs, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Of 3384 unique citations, 51 studies met inclusion criteria. Studies included melanoma (n = 21), lung (n = 19), renal (n = 4), urothelial (n = 1), head and neck (n = 2) and gastrointestinal cancers (n = 1). In patients with metastatic melanoma (n = 1474), the development of irAEs (irAE + versus irAE-) was associated with better weighted average OS (15.24 months (95% CI 9.95 to 20.5) versus 8.94 months (95% CI 7.76 to 10.1), HR = 0.46 (n = 640, CI 0.35-0.62, p < 0.00001), PFS (17.61 months (95% CI 10.1 to 25.1) versus 2.23 months (95% CI 1.77 to 2.68), HR = 0.51 (n = 1763, CI 0.42-0.63, p < 0.00001), and ORR (37.67% (95% CI 32.8 to 42.5) versus. 23.44% (95% CI 17.8 to 29.1). Similarly, in lung cancer patients, the ORR (irAE + versus. irAE-) was 41.49% (95% CI 36.5 to 46.5) versus 18.01% (95% CI 13.5 to 22.6). The weighted average PFS and OS were 8.97 months (95% CI 7.14 to 10.8) versus 3.06 months (95% CI 2.4 to 3.72) with HR = 0.46 (n = 1575, CI 0.39-0.54, p < 0.00001) and 19.07 months (95% CI 14.3 to 23.8) versus 7.45 months (95% CI 5.34 to 9.56) HR = 0.40 (n = 1085, CI 0.30-0.51, p < 0.00001), respectively. Improved treatment efficacy in patients who developed irAEs was also seen in renal cell carcinoma, urothelial and head and neck cancers. Notably, grade 3 or 4 irAEs were associated with increased ORR but worse OS. CONCLUSION: A positive association was noted between the development of irAEs and ORR, PFS, and OS in patients treated with ICIs, irrespective of disease site, type of ICI and irAE. Grade 3 or higher toxicities resulted in better ORR, but worse OS.
Authors: Clara Faubry; Maxime Faure; Anne-Claire Toublanc; Rémi Veillon; Anne-Iris Lemaître; Charlotte Vergnenègre; Hubert Cochet; Sadia Khan; Chantal Raherison; Pierre Dos Santos; Maeva Zysman Journal: Front Cardiovasc Med Date: 2022-06-06