Bożena Cybulska-Stopa1, Marcin Ziętek2,3, Anna M Czarnecka4,5, Karolina Piejko1, Robert Dziura6, Łukasz Galus7,8, Barbara Ziółkowska9, Stanisław Kieszko10, Natasza Kempa-Kamińska11, Jacek Calik11, Joanna Seredyńska1, Kamila Gądek1, Tomasz Zemełka1, Paweł Teterycz4, Tomasz Kubiatowski10, Rafał Suwiński9, Jacek Mackiewicz7,12, Piotr Rutkowski4. 1. Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Poland. 2. Department of Oncology, Wrocław Medical University, Wrocław, Poland. 3. Department of Surgical Oncology, Wrocław Comprehensive Cancer Center, Wrocław, Poland. 4. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 5. Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. 6. Clinical Oncology Department, Holy Cross Cancer Center, Kielce, Poland. 7. Department of Medical and Experimental Oncology, University of Medical Sciences, Poznan, Poland. 8. Chemotherapy Department, Greater Poland Cancer Centre, Poznan, Poland. 9. II Clinic of Radiotherapy and Chemotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. 10. Department of Clinical Oncology, Saint Jan of Dukla Oncology Centre of the Lublin Region, Lublin, Poland. 11. Department of Clinical Oncology, Wrocław Comprehensive Cancer Center, Wroclaw, Poland. 12. Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
Abstract
BACKGROUND: The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. MATERIAL AND METHODS: Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. RESULTS: Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). CONCLUSION: The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.
BACKGROUND: The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. MATERIAL AND METHODS: Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. RESULTS: Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). CONCLUSION: The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.