Outcome of immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines

Abstract

Background: Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines. Patients and methods: This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI þ tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively. Conclusions: ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

“…This is partially due to the exclusion of heavily pre‐treated patients from most clinical trials, which are predominantly arranged in the 1 and 2 L settings. The 4 L setting has not been extensively investigated and these data are mostly from retrospective studies, which do not include patients who progressed to both nivolumab and cabozantinib 4,5,16,17,22–25 …”

FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy

“…After the successes of IO therapy in patients with disease progression on conventional targeted therapies, the randomized phase 3 pivotal CheckMate 214 trial evaluated combination immune checkpoint blockade in treatment-naïve patients with advanced clear cell RCC, resulting in FDA approval of nivolumab plus ipilimumab in patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate or poor risk. 9 13 14 Thereafter, approaches incorporating dual immune checkpoint blockade with a PD-1 or programmed death ligand 1 (PD-L1) inhibitor along with cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibition, or immune checkpoint blockade plus a vascular endothelial growth factor (VEGF)-targeted therapy, has become an accepted standard of care for treatment-naïve aRCC on the basis of unprecedented response rates and improved survival. 1–10 Nivolumab is now widely used in monotherapy or in combination for the treatment of aRCC, and the clinical benefit of IOs and their combination with antiangiogenic agents is evident in both untreated and treated patients with aRCC.…”

“… 1 9 15 16 In clinical practice, the potential benefits of ICIs or ICI combinations when given beyond the first-line and second-line setting have not been fully elucidated. 9 13 When patients develop resistance or toxicity to immune checkpoint blockade in the first-line treatment of aRCC, a new challenge has emerged regarding how to optimally treat patients in the second-line and beyond in patients who have received prior IO therapy. 1 2 13 Several studies investigated the addition of ipilimumab to nivolumab in a sequential manner and showed that this approach was not always feasible and of limited benefit, with efficacy appearing to be less than that of concomitant nivolumab plus ipilimumab in untreated patients with intermediate/poor-risk disease (CheckMate 214 trial).…”

“…9 13 14 Thereafter, approaches incorporating dual immune checkpoint blockade with a PD-1 or programmed death ligand 1 (PD-L1) inhibitor along with cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibition, or immune checkpoint blockade plus a vascular endothelial growth factor (VEGF)-targeted therapy, has become an accepted standard of care for treatment-naïve aRCC on the basis of unprecedented response rates and improved survival. [1][2][3][4][5][6][7][8][9][10] Nivolumab is now widely used in monotherapy or in combination for the treatment of aRCC, and the clinical benefit of IOs and their combination with antiangiogenic agents is evident in both untreated and treated patients with aRCC. 3 11 15 IO options currently constitute the backbone of both first-line and second-line treatments.…”

DataSheet1.ZIP

“…Non-specificity and drug resistance are the main problems faced by conventional treatments for ccRCC (Gai et al, 2020;Zou et al, 2021). And the role of lncRNA in cancer is receiving increasing attention from researchers (Inthagard et al, 2019;Resch et al, 2021).…”