Background The recent therapeutic advancements based on immune-oncology (IO) combinations have revolutionized the renal cell carcinoma (RCC) management. However, a subset of patients, termed "primary refractory (Pref)", faces dismal outcomes. Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref metastatic RCC patients. Methods This study collected data from 72 centers across 22 countries worldwide, involving patients aged ≥18 with metastatic clear cell RCC. All enrolled patients were treated with first-line IO combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors 1.1 criteria. Statistical analyses employed Kaplan-Meier, Cox proportional hazard models, logistic regression, and receiver operating characteristic curve analysis. Results Among 1709 patients, 19% exhibited primary refractoriness. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Pref patients demonstrated significantly lower median overall survival (OS) (7.6 months) compared to non-Pref patients (55.7 months) (p<.01). Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium (IMDC) risk, no nephrectomy, sarcomatoid de-differentiationand and increased risk of Pref. At the multivariate analysis nephrectomy, sarcomatoid de-differentiation, intermediate/poor IMDC risk, bone and brain metastases emerged as significant predictors of OS for Pref RCC patients. Stratification based on clinical-pathological features emphasized the negative impact of IMDC (intermediate/poor), metastatic sites (bone and brain), Neutrophil-to-Lymphocyte ratio (≥4), and the number of metastatic sites (≥2) on the Pref outcomes. Conclusions The ARON-1 study provides valuable insights into Pref mRCC patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
1716P Primary resistance to front-line immune-based combinations in patients with advanced renal cell carcinoma (ARON-1) / Catalano, M.; Roviello, G.; Buti, S.; Massari, F.; Li, H.; Park, S. H.; Grande, E.; Kucharz, J.; Fiala, O.; Poprach, A.; Buchler, T.; Seront, E.; Ansari, J.; Myint, Z. W.; Bhuva, D. M.; Bamias, A.; Ghosn, M.; Andrey, S.; Santoni, M.; Santini, D.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 35:Supplement 2(2024), pp. S1028-S1029. [10.1016/j.annonc.2024.08.1809]
1716P Primary resistance to front-line immune-based combinations in patients with advanced renal cell carcinoma (ARON-1)
Buti, S.Investigation
;
2024-01-01
Abstract
Background The recent therapeutic advancements based on immune-oncology (IO) combinations have revolutionized the renal cell carcinoma (RCC) management. However, a subset of patients, termed "primary refractory (Pref)", faces dismal outcomes. Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref metastatic RCC patients. Methods This study collected data from 72 centers across 22 countries worldwide, involving patients aged ≥18 with metastatic clear cell RCC. All enrolled patients were treated with first-line IO combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors 1.1 criteria. Statistical analyses employed Kaplan-Meier, Cox proportional hazard models, logistic regression, and receiver operating characteristic curve analysis. Results Among 1709 patients, 19% exhibited primary refractoriness. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Pref patients demonstrated significantly lower median overall survival (OS) (7.6 months) compared to non-Pref patients (55.7 months) (p<.01). Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium (IMDC) risk, no nephrectomy, sarcomatoid de-differentiationand and increased risk of Pref. At the multivariate analysis nephrectomy, sarcomatoid de-differentiation, intermediate/poor IMDC risk, bone and brain metastases emerged as significant predictors of OS for Pref RCC patients. Stratification based on clinical-pathological features emphasized the negative impact of IMDC (intermediate/poor), metastatic sites (bone and brain), Neutrophil-to-Lymphocyte ratio (≥4), and the number of metastatic sites (≥2) on the Pref outcomes. Conclusions The ARON-1 study provides valuable insights into Pref mRCC patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
