Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W. Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni
{"title":"晚期肾细胞癌患者对一线免疫疗法联合用药的真实世界原发性耐药性（ARON-1）","authors":"Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W. Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni","doi":"10.1007/s11523-024-01096-3","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (<i>P</i><sub>ref</sub>), face dismal outcomes.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of <i>P</i><sub>ref</sub> patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In our study, the <i>P</i><sub>ref</sub> rate was 19%. Nivolumab/ipilimumab showed the highest <i>P</i><sub>ref</sub> rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-<i>P</i><sub>ref</sub> patients (55.7 months), <i>p</i> < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for <i>P</i><sub>ref</sub> patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of <i>P</i><sub>ref</sub>. This study presents limitations, mainly because of its retrospective design.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The ARON-1 study provides valuable insights into <i>P</i><sub>ref</sub> patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":"40 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)\",\"authors\":\"Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Enrique Grande, Jakub Kucharz, Umberto Basso, Ondrej Fiala, Fernando Sabino Marques Monteiro, Alexandr Poprach, Sebastiano Buti, Javier Molina-Cerrillo, Martina Catalano, Tomas Buchler, Emmanuel Seront, Jawaher Ansari, Zin W. Myint, Marwan Ghosn, Fabio Calabrò, Ray Manneh Kopp, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Andrey Soares, Nicola Battelli, Marco Ricci, Ravindran Kanesvaran, Aristotelis Bamias, Camillo Porta, Francesco Massari, Matteo Santoni\",\"doi\":\"10.1007/s11523-024-01096-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (<i>P</i><sub>ref</sub>), face dismal outcomes.</p><h3 data-test=\\\"abstract-sub-heading\\\">Objective</h3><p>Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of <i>P</i><sub>ref</sub> patients.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>In our study, the <i>P</i><sub>ref</sub> rate was 19%. Nivolumab/ipilimumab showed the highest <i>P</i><sub>ref</sub> rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-<i>P</i><sub>ref</sub> patients (55.7 months), <i>p</i> < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for <i>P</i><sub>ref</sub> patients with renal cell carcinoma. 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Real-World Primary Resistance to First-Line Immune-Based Combinations in Patients with Advanced Renal Cell Carcinoma (ARON-1)
Background
Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (Pref), face dismal outcomes.
Objective
Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients.
Methods
This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve.
Results
In our study, the Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-Pref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for Pref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of Pref. This study presents limitations, mainly because of its retrospective design.
Conclusions
The ARON-1 study provides valuable insights into Pref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
期刊介绍：
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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