Therapeutic sequencing in the era of first-line immune checkpoint inhibitor combinations, a novel challenge in patients with metastatic clear-cell renal cell carcinoma.

Immune checkpoint inhibitor combinations have reshaped the treatment landscape of metastatic clear-cell renal cell carcinoma. As four regimens are now approved in the first-line setting, including nivolumab plus ipilimumab in intermediate and poor-risk patients, and pembrolizumab plus lenvatinib, nivolumab plus cabozantinib and pembrolizumab plus axitinib in all-comers, the choice of subsequent therapies is becoming a novel challenge for physicians. Such choices now rely on several compounds used as monotherapy which have demonstrated sustained activity after previous immune checkpoint or tyrosine kinase inhibitors. Future strategies may lie in novel targets, including hypoxia-inducible factor inhibitors, as well as further exploration of combinations in more advanced settings. Here we review the current evidence regarding treatment activity after immune checkpoint inhibitor combinations, the underlying biological and clinical challenges that may impact patient selection and the optimal sequencing strategies for clinical practice.

Accelerated partial breast irradiation in the elderly: 8-year oncological outcomes and prognostic factors.

PURPOSE: The purpose of the study is to evaluate long-term clinical outcomes and prognostic factors after accelerated partial breast irradiation (APBI) in the elderly using high-dose-rate interstitial multicatheter brachytherapy (HIBT). METHODS AND MATERIALS: Between 2005 and 2018, 109 patients underwent APBI using HIBT (34 Gy/10f/5d or 32 Gy/8f/4d). Based on a prospective database, outcomes were retrospectively analyzed (local relapse-free survival, metastatic-free survival, specific survival (SS), and overall survival (OS)). Prognostic factors were investigated. Late toxicity and cosmetic evaluation were reported. RESULTS: With a median followup of 97 months [7-159], median age was 81.7 years [58-89]. In accordance with the GEC-ESTRO APBI classification, 72.5%, 11.9%, and 15.6% were classified as low, intermediate, and high risk, respectively. The histological type was mainly invasive ductal carcinoma (87.1%). The median tumor size was 10 mm [range 1-35]. Eight-year local relapse-free survival, SS, and OS were 96.7% [95% confidence interval (CI) [0.923; 1]), 96.7% [95% CI [0.924; 1], and 72% [95% CI [0.616; 0.837], respectively. In univariate analysis, APBI classification was not considered as prognostic factor, whereas molecular classification was prognostic factor for OS (p < 0.0001), SS (p = 0.007), and metastatic-free survival (p = 0.009) but not for local recurrence (p = 0.586). No Grade ≥3 late toxicity was observed, whereas 61 patients (88.4%) and 8 patients (11.6%) presented Grade 1 and 2 toxicities, respectively. The cosmetic outcome was excellent/good for 96.4%. CONCLUSIONS: Long-term followup confirms that HIBT is safe and effective for elderly early breast cancer. Our results suggest that selected elderly women presenting with high-risk breast cancer could be also considered for APBI.