Fraterman and Reijers et al. evaluated the association between pretreatment emotional distress (ED) and clinical response in stage III melanoma patients treated with neoadjuvant ICB in phase II PRADO trial. Patients with pretreatment ED showed a reduced MPR (46% versus 65%) and significantly impaired 2-year RFS (74% versus 91%) and 2-year DMFS (78% versus 95%) compared with patients without ED, after adjusting for the previously identified baseline biomarkers (IFNγ signature and TMB). Transcriptional analyses of baseline β-Adrenergic- or glucocorticoid-associated pathways did not show significant association with ED.
Contributed by Shishir Pant
ABSTRACT: Neoadjuvant immune checkpoint blockade (ICB) outperforms adjuvant ICB for treatment of stage IIIB-D melanoma, but potential biomarkers of response, such as interferon-gamma (IFNγ) signature and tumor mutational burden (TMB), are insufficient. Preclinical studies suggest that emotional distress (ED) can negatively affect antitumor immune responses via β-adrenergic or glucocorticoid signaling. We performed a post hoc analysis evaluating the association between pretreatment ED and clinical responses after neoadjuvant ICB treatment in patients with stage IIIB-D melanoma in the phase 2 PRADO trial ( NCT02977052 ). The European Organisation for Research and Treatment of Cancer scale for emotional functioning was used to identify patients with ED (n = 28) versus those without (n = 60). Pretreatment ED was significantly associated with reduced major pathologic responses (46% versus 65%, adjusted odds ratio 0.20, P = 0.038) after adjusting for IFNγ signature and TMB, reduced 2-year relapse-free survival (74% versus 91%, adjusted hazard ratio 3.81, P = 0.034) and reduced 2-year distant metastasis-free survival (78% versus 95%, adjusted hazard ratio 4.33, P = 0.040) after adjusting for IFNγ signature. RNA sequencing analyses of baseline patient samples could not identify clear β-adrenergic- or glucocorticoid-driven mechanisms associated with these reduced outcomes. Pretreatment ED may be a marker associated with clinical responses after neoadjuvant ICB in melanoma and warrants further investigation. ClinicalTrials.gov registration: NCT02977052 .
Author Info: (1) Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. (2) Department of Medical Oncology, Netherlands Cancer Institute
Author Info: (1) Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. (2) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. (3) Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands. (4) Core Facility and Molecular Pathology & Biobanking Department, Netherlands Cancer Institute, Amsterdam, the Netherlands. (5) Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia. (6) Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia. Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia. (7) Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands. (8) Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. (9) Departments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. (10) Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. (11) Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. (12) Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia. Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia. Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. (13) Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands. (14) Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. l.vd.poll@nki.nl. Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands. l.vd.poll@nki.nl. Department of Medical and Clinical Psychology, Center of Research on Psychological and Somatic Disorders (CoRPS), Tilburg University, Tilburg, the Netherlands. l.vd.poll@nki.nl.
