Ines Pires da Silva1,2, Serigne Lo1,2, Camelia Quek1,2, Maria Gonzalez1, Matteo S Carlino1,3,4, Georgina V Long1,5,6, Alexander M Menzies1,5,6. 1. Melanoma Institute Australia, Sydney, New South Wales, Australia. 2. Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. 3. Western Clinical School, The University of Sydney, Sydney, New South Wales, Australia. 4. Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia. 5. Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia. 6. Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
Abstract
BACKGROUND: Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti-PD-1 therapy (IPI + PD1) and to explore the nature of pseudoprogression and acquired resistance. METHODS: Patients with metastatic melanoma who received treatment with first-line IPI + PD1 had all metastases ≥5 mm measured on computed tomography/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17 mm; P < .0001). Soft-tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR (odds ratio [OR], 2.75; P = .02) and progression-free survival (hazard ratio [HR], 0.46; P = .02), whereas those with liver metastases had inferior ORR (OR, 0.33; P = .02), progression-free survival (HR, 4.03; P < .01), and overall survival (HR, 3.17; P = .01). Pseudoprogression occurred in one-third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6 months, with an overall survival rate of 83% at 1 year from progression. CONCLUSIONS: Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.
BACKGROUND:Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti-PD-1 therapy (IPI + PD1) and to explore the nature of pseudoprogression and acquired resistance. METHODS:Patients with metastatic melanoma who received treatment with first-line IPI + PD1 had all metastases ≥5 mm measured on computed tomography/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17 mm; P < .0001). Soft-tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR (odds ratio [OR], 2.75; P = .02) and progression-free survival (hazard ratio [HR], 0.46; P = .02), whereas those with liver metastases had inferior ORR (OR, 0.33; P = .02), progression-free survival (HR, 4.03; P < .01), and overall survival (HR, 3.17; P = .01). Pseudoprogression occurred in one-third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6 months, with an overall survival rate of 83% at 1 year from progression. CONCLUSIONS:Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.
Authors: Ines Pires da Silva; Danny Zakria; Tasnia Ahmed; Claudia Trojanello; Florentia Dimitriou; Clara Allayous; Camille Gerard; Lisa Zimmer; Serigne Lo; Olivier Michielin; Celeste Lebbe; Johanna Mangana; Paolo Antonio Ascierto; Douglas B Johnson; Matteo Carlino; Alexander Menzies; Georgina Long Journal: J Immunother Cancer Date: 2022-07 Impact factor: 12.469
Authors: James C Lee; Sadaf Mehdizadeh; Jennifer Smith; Arabella Young; Ilgiz A Mufazalov; Cody T Mowery; Adil Daud; Jeffrey A Bluestone Journal: Sci Immunol Date: 2020-10-02
Authors: James C Lee; Michael D Green; Laura A Huppert; Christine Chow; Robert H Pierce; Adil I Daud Journal: Clin Cancer Res Date: 2021-07-20 Impact factor: 12.531
Authors: Andrea Ronchi; Marco Montella; Federica Zito Marino; Giuseppe Argenziano; Elvira Moscarella; Gabriella Brancaccio; Giuseppe Ferraro; Giovanni Francesco Nicoletti; Teresa Troiani; Renato Franco; Immacolata Cozzolino Journal: Cancer Cytopathol Date: 2021-07-26 Impact factor: 4.264