A phase 2 single-arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pretreated with one immune checkpoint inhibitor: The BREAKPOINT trial (MeetUro trial 03-NCT03463681).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4569-4569
Author(s):  
Giuseppe Procopio ◽  
Melanie Claps ◽  
Chiara Pircher ◽  
Luca Porcu ◽  
Pierangela Sepe ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Oral Mucositis ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
First Line

4569 Background: For many years, vascular endothelial growth factor (VEGF)-targeted therapy (tp) has been a milestone for metastatic renal cell carcinoma (mRCC). Recently, first line tp based on anti-PD-1/PD-L1 immune-checkpoint inhibitors (ICIs) plus tyrosine-kinase-inhibitors (IO-TKI) and anti-PD-1 plus anti-CTLA-4 combos (IO-IO) significantly improved survival of mRCC patients (pts). Prospective data are lacking to determine the efficacy of anti-VEGF tp after IO-IO or IO-TKI. Cabozantinib (Cabo) showed to prolong survival in mRCC pts pre-treated with TKIs and to target kinases involved in immune-escape. So, it may represent an ideal agent to be used sequentially after ICIs. Methods: This is an open label, single arm, multicenter, phase II study evaluating efficacy and safety of Cabo in mRCC pts who received an anti-PD-1/PD-L1-based adjuvant (adj) or first line tp. Cabo 60 mg/daily was administered until progressive disease (PD) or unacceptable toxicity. Primary endpoint was progression free survival (PFS) by Brookmeyer-Crowley test, secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Exploratory endopoints were to investigate tissue PD-L1 expression, to assess the modulating activity of Cabo on local and systemic tumor immunity and to explore bone formation and reabsorption markers. Results: From July 2018, 49 pts were enrolled and 48 were included in the analysis. Median age was 62.5 years (range: 30-78), 63% of pts were male. At baseline, 26% of pts had a good Heng risk score, 47% intermediate and 28% a poor risk, while in 2% of pts the class of risk was undetermined. 74% of pts received an IO-IO combo as first line tp, 17% IO-TKI, 9% pts an adj IO monotherapy. Pts received a median of 10 cycles of Cabo (range 5-17 cycles). 25 pts (53%) are still on tp, 1 patient discontinued Cabo for AEs, 13 pts for radiological PD, 6 pts discontinued for clinical PD or death, while 2 pts for reasons other than AEs or PD. Among evaluable cases, 17 pts (43%) achieved a partial response and 15 pts (37%) stable disease. Complete responses were not observed. At a median (m) follow-up of 8.0 months (mo) (4.4-13.5 mo), 71% of pts were alive and mPFS was 9.3 mo (95% CI 7.1-29.0 mo). Grade (G) 3-4 adverse events (AEs) occurred in 34% of pts, including more frequently serum bilirubin increase, hypertension, calcium and sodium serum levels alterations and oral mucositis. G1-2 were observed in 61% of pts, including in most of cases diarrhoea, nausea, oral mucositis, disgeusia, hand-foot syndrome, fatigue and hypothyroidism. Due to AEs, transitory withholding of Cabo was observed in 53.5% of pts and for 23 pts (48%) dose reductions were needed. Conclusions: So far, Cabo tp after IO-IO or IO-TKI showed promising results and was well tolerated. Longer follow-up is needed for final OS and exploratory endpoints results. Clinical trial information: NCT03463681.

A phase II open-label study of cabozantinib after first-line treatment including an immune-checkpoint combination in patients with advanced or unresectable renal cell carcinoma: The BREAKPOINT trial (MeetUro trial 03 - EudraCT number 2018-000582-36).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 326-326
Author(s):  
Giuseppe Procopio ◽  
Chiara Pircher ◽  
Melanie Claps ◽  
Valentina Guadalupi ◽  
Alessia Mennitto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
First Line ◽  
Open Label

326 Background: Antiangiogenic therapy has been a milestone in the treatment of metastatic renal cell carcinoma (mRCC) for years. The positive results with immune-checkpoint inhibitors (ICI) are changing the frontline standard of care of mRCC patients (pts). To date, prospective data are lacking to determine the efficacy of antiangiogenic therapy in pts progressed to ICI. The multikinase inhibitor Cabozantinib (cabo) has shown prolonged survival in pre-treated mRCC pts. Moreover, by targeting multiple pathways and crucial kinases involved in microenvironment-driven immune-escape, it may represent an ideal agent to be used sequentially after ICI. Methods: This is the first prospective open label, single arm, multicenter, phase II study to evaluate efficacy and safety of Cabo in pts with mRCC pre-treated with adjuvant or first line PD-1/PD-L1-based therapy (as monotherapy or in combination with an TKI or anti CTLA-4). Cabo 60 mg once daily was administered until progressive disease (PD) or unacceptable toxicity. The primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Results: Among 23 patients enrolled, 22 were included in the analysis (one was excluded for screening failure). Median age was 59.5 years (range: 29-74), 69.5% were male. At baseline, Karnofsky performance status was 100 in 59% of pts, 80-90 in 31.8% and 70-80 in 9%. 22.7% of pts had a good Heng score, 50% intermediate and 27.2% poor. Median duration of the previous therapy with anti PD-1 or anti-PD-L1 compounds was 4.3 months. Pts received an average of 4.7 months of Cabo. Among evaluable cases, 6 pts (27.2%) achieved a partial response and 5 pts (22.7%) stable disease. The median follow-up was 7.2 months and the median PFS was 7.2 months. 2 pts discontinued treatment for toxicity, 8 pts for PD, 1 patient discontinued treatment for different reason than PD, 11 pts are still on treatment. Grade (G) 3 adverse events (AEs) occurred in 22.7% of pts; the most common AEs were hand and foot syndrome (HFS) (G1 in 36.3% of pts, G2 18.1%, G3 4.5%), diarrhea (G1 31.8%, G2 18.1%), hypothyroidism (G1 9.09 %, G2 22.7 %), mucositis (G1 36.3%, G2 4,5%), and fatigue (G1 18.1%, G2 18.1%). Transitory withholding of cabo was observed in 63.6% of pts (14/22) and it was due to AEs in the 90% of the cases. For 5/22 pts (22.7 %), dose reduction was needed to manage AEs. The most common AEs leading to temporary drug interruption were HFS G1-3 (13.9%), liver disfunction G1-G2 (13.9%), diarrhea G1-G2 (11.6%), nausea and vomiting G2 (11.6 %) and fatigue G2 (9.3%). Conclusions: So far, the treatment with cabo after a I line anti-PD-1 based immunotherapy resulted active and well tolerated. Clinical trial information: NCT03463681 .

A phase II open-label study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pretreated with one immune-checkpoint inhibitor: The BREAKPOINT trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS685-TPS685 ◽  
Author(s):  
Elena Verzoni ◽  
Alessandra Bearz ◽  
Ugo De Giorgi ◽  
Franco Nole ◽  
Camillo Porta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
First Line ◽  
Open Label

TPS685 Background: First-line treatment landscape of metastatic renal cell carcinoma (mRCC) is evolving with strong evidence in favour of PD-1/PD-L1 combinations over tyrosine kinase inhibitors (TKIs). No prospective data about efficacy of TKIs post immune-checkpoint inhibitor (CPI) combinations are available. Among TKIs, cabozantinib has demonstrated progression-free survival (PFS) and overall survival (OS) benefit over everolimus in pre-treated mRCC patients (pts). Methods: Overall 49 mRCC pts who received a previous CPI (anti PD-1/PD-L1) will be treated with cabozantinib. Pts will be stratified according to Heng prognostic group, duration of first-line and type of previous therapy received (CPI+CPI or CPI+TKI or CPI+anti-VEGF or CPI monotherapy). Key inclusion criteria include: one previous treatment with a PD-1/PD-L1 inhibitor in first-line and histological diagnosis of clear-cell RCC. The primary endpoint is to assess the efficacy of cabozantinib based on PFS. Secondary endpoints include evaluation of OS, objective response rate and safety profile of the drug. Exploratory endpoints include evaluation of PD-L1 levels by immunohistochemistry in tumor samples; the analysis of the immunological signature/profile of tumor cells; the state of circulating immune cells, as well as the modulating activity of cabozantinib on systemic tumor immunity; the evaluation of bone formation and reabsorption markers in pts with or without bone involvement. Cabozantinib will be administered orally at a dose of 60 mg/day continuously until evidence of disease progression or onset of unacceptable toxicity. Statistical design: By the methodology of Brookmeyer and Crowley, assuming an accrual period of 18 months and a minimum follow-up of 10 months (mos), 49 pts are necessary to detect an increment of the median PFS time from 3.8 mos to 7.4 mos with a power of 90% and one-sided alpha of 5%. The large sample critical value detecting the increment of the PFS median survival time will be 5.54 mos. To date, 2 pts have been enrolled. Clinical trial information: NCT03463681.

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

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 651-651
Author(s):  
Andreas Bruchbacher ◽  
Johannes Franke ◽  
Zumreta Alic ◽  
Sebastian Nachbargauer ◽  
Harun Fajkovic ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
Entire Cohort ◽  
Treatment Line

651 Background: The introduction of immune checkpoint inhibitors (ICPI) has led to a paradigm change in the management of metastatic Renal Cell Carcinoma (mRCC). Prospective trials focused on ICPI treatment in first- or second-line. The aim of this analysis was to evaluate the benefit of ICPI across different treatment lines. Methods: This is a single center retrospective study from the Medical University of Vienna which included all mRCC patients who received ICPIs in various treatment lines. Overall response rates (ORR), progression free survival (PFS) and overall survival (OS) were evaluated for the entire cohort and by treatment line. Results: Between January 2014 and October 2019, a total of 113 patients received ICPIs. Ninety-four patients were eligible for full evaluation (83% clear cell and 17% non-clear cell). 26.8%, 61.6% and 14.8% were classified good, intermediate and poor IMDC-risk, respectively. 59%, 20% and 21% were treated with ICPI monotherapy, dual ICPI therapy and ICPI + tyrosine kinase inhibitor, respectively. ORR, median PFS and median OS for the entire cohort was 39.4%, 9.67 months (95%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-line (9 patients), 40.4%, in second- (42 patients), 35% in third- (20 patients) and 43.5% in fourth and beyond-fourth-line (23 patients). The median PFS by treatment line was: 8.6 months, 10.3 months, 7.9 months and 7.23 months, respectively. The median OS was not reached (NR) in first-line and 26.2 months, 18.1 months and 20.7 months in second-, third-, and fourth and beyond- ICPI treatment line, respectively. The global OS for the whole patient cohort calculated from diagnosis of metastasis was 80 months (CL 95%: 50.5 – 109.5 months). Conclusions: ICPIs are active in all treatment lines and should also be offered in heavily pre-treated patients, who have not had access in earlier treatment lines.

Patient-reported outcomes of patients with advanced renal cell carcinoma (aRCC) treated with first-line nivolumab plus cabozantinib versus sunitinib: The CheckMate 9ER trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 285-285
Author(s):  
David Cella ◽  
Toni K. Choueiri ◽  
Steven I. Blum ◽  
Flavia Ejzykowicz ◽  
Melissa Hamilton ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Well Being ◽  
Phase Iii ◽  
First Line ◽  
Patient Reported

285 Background: In the phase III, open-label CheckMate 9ER trial (NCT03141177), patients with aRCC were randomized 1:1 (stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk score, tumor programmed death ligand 1 expression, geographic region) to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD (N+C; n = 323) or sunitinib (S) 50 mg PO (4 weeks of 6-week cycles; n = 328) for first-line treatment until disease progression or unacceptable toxicity (max N treatment, 2 years). N+C met primary and secondary efficacy endpoints by significantly improving progression-free survival, overall survival, and objective response rate versus S in aRCC patients with a clear cell component. Here, we present in-depth health-related quality of life (HRQoL) patient-reported outcome (PRO) results, including overall between-group comparisons of treatment groups and time to confirmed deterioration (TCD). Methods: PROs in all randomized patients were an exploratory endpoint assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) and EQ-5D-3L instruments. PRO assessments at baseline, common on-treatment scheduled visits, and common follow-up visits for both arms were analyzed. Changes from baseline were assessed using mixed-model repeated measures (MMRM), adjusting for baseline scores and stratification factors. TCD was calculated from Kaplan–Meier estimates and Cox proportional hazards models. Results: Median follow-up for overall survival was 18.1 months. PRO completion rates were > 90% at baseline, and ≥ 80% at all on-treatment assessments (≥ 10 patients) through week 91 in both arms. The overall least squares mean difference in change from baseline favored N+C over S in FKSI-19 (all domains) and in EQ-5D-3L. Patients treated with N+C experienced less treatment burden, with decreased risk of confirmed deterioration across most measurements versus S, including FKSI-19 total, disease-related symptoms (DRS), DRS-physical (DRS-P), DRS-emotional (DRS-E), functional well-being (FWB), and EQ-5D-3L visual analog scale (VAS) scores (Table). Conclusions: Patients reported statistically significant HRQoL benefits with N+C versus S. Treatment with N+C significantly reduced the risk of deterioration in HRQoL scores, including in disease-related symptoms of kidney cancer. These results suggest that the superior efficacy of N+C over S comes with the additional benefit of improved HRQoL. Clinical trial information: NCT03141177 . [Table: see text]

scholarly journals Acute interstitial nephritis, a potential predictor of response to immune checkpoint inhibitors in renal cell carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001198
Author(s):  
Viral Patel ◽  
Roy Elias ◽  
Joseph Formella ◽  
William Schwartzman ◽  
Alana Christie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
First Line ◽  
Improved Outcomes

Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab have improved outcomes in metastatic renal cell carcinoma (mRCC) patients, but they are also associated with immune-related adverse events (irAEs). As observed in melanoma, we hypothesized that patients experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we asked whether patients with immune-related acute interstitial nephritis (irAIN) exhibited improved outcomes. Using Kidney Cancer Explorer (KCE), a data portal and i2b2-based central database for clinical, pathological and experimental genetic data, we systematically identified all patients with mRCC at UT Southwestern Medical Center (UTSW) from 2014–2018 who received at least one dose of ICI. More recent cases were identified through a provider query. We extracted creatinine (Cr) values at baseline and over the entirety of each patient ICI treatment course using KCE. Patients with ≥ 1.5-fold Cr increase over baseline were investigated. The likelihood of irAIN was determined based on the work-up (biopsy, if available), or by clinical criteria (timing of kidney injury, exclusion of other etiologies, treatment with immunosuppressants and response). We identified 177 mRCC patients who received at least one dose of ICI, 36 of whom had ≥ 1.5-fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven irAIN and one was clinically diagnosed, resulting in an incidence of 1.7%. One additional biopsy-proven case past 2018 was identified through a provider query, for a total of four patients. Two received combination nivolumab and ipilimumab in the first line, whereas the remaining received nivolumab after first line therapy. irAIN onset ranged from 1.5 to 12 months. All four patients stopped ICI with recovery of renal function, at least partially, three after receiving systemic steroids. Notably, all four patients had a deep response. In conclusion, irAIN is a rare event, but it may portend a higher likelihood of response. One possible explanation is antigenic overlap between normal renal tubular cells and tumor cells.

255 Efficacy of sequential immune checkpoint inhibition (ICI) in patients with genitourinary malignancies

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A277-A278
Author(s):  
Sean Evans ◽  
Dylan Martini ◽  
Benjamin Magod ◽  
Timothy Olsen ◽  
Jacqueline Brown ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Renal Cell ◽  
Objective Response ◽  
First Line ◽  
Entire Cohort ◽  
Emory University ◽  
Treatment Data

BackgroundImmune checkpoint inhibitors (ICI) have become a standard of care for treatment of both metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC). Additional treatment with ICI following disease progression on first-line therapy has become increasingly common for patients with severe disease, but the clinical outcomes of sequential therapy have not been well studied. We report here the clinical outcomes in a cohort of patients with mRCC and mUC who received two regimens of ICI-based therapy.MethodsWe performed a retrospective review of 31 mRCC patients and 11 mUC with follow-up data available who received at least 1 dose of a 2nd ICI-based regimen at the Winship Cancer Institute of Emory University from 2015–2020. Radiographic responses were determined using response evaluation criteria in solid tumors version 1.1 (RECISTv1.1). An objective response (OR) was defined as a complete response (CR) or partial response (PR). Clinical benefit (CB) was defined as an objective response or stable disease (SD) > 6 months.ResultsMost patients were white (81%) and male (69%). 31 had mRCC (table 1) and 11 had mUC (table 2). Overall most patients (58%) received anti-PD-1 (Programmed cell death protein 1) monotherapy as first line, with anti-PD-L1 (Programmed death-ligand 1) monotherapy (33%) and anti-PD-1/CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) combination therapy (9%) being less prevalent. Patients spent an average of 27.1 weeks on first ICI therapy. Second ICI-based treatment was most commonly anti-PD-1/CTLA-4 (62%), followed by anti-PD-1 monotherapy (38%). A subset of patients (33%) had clinical benefit with combination anti-PD-1/CTLA-4-based second ICI therapy, with 4 (10%) having PR and one (2%) having CR of disease following second ICI-based treatment. Patients spent an average of 21.4 weeks on the second ICI regimen. The response rate for the entire cohort was 11.9% (16.7% for RCC and 0% for UC).The CB rate for the entire cohort was 40% (40% for RCC and 40% for UC). Immune-related adverse events were experienced in a subset of patients (28%).Abstract 255 Table 1Demographics and treatment data for patients with metastatic renal cell carcinomaAbstract 255 Table 2Demographics and treatment data for patients with urothelial cell carcinomaConclusionsAlthough we observed a low OR rate to a second ICI-based regimen, a select subset of patients did have CB from a second ICI-regimen. Current studies exploring the addition of CTLA4 inhibitors to anti-PD-1 therapy may provide insight into the greater efficacy of treatment within a subset of patients. Further analysis of a larger cohort receiving sequential immunotherapy is necessary to better identify patients who may be more likely to derive CB from sequential ICI.Ethics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicable.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation.Trial RegistrationNot applicable.ReferencesNot applicable

scholarly journals Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001079 ◽  
Author(s):  
Laurence Albiges ◽  
Nizar M Tannir ◽  
Mauricio Burotto ◽  
David McDermott ◽  
Elizabeth R Plimack ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma ◽  
Risk Category ◽  
First Line

PurposeTo report updated analyses of the phase III CheckMate 214 trial with extended minimum follow-up assessing long-term outcomes with first-line nivolumab plus ipilimumab (NIVO+IPI) versus (vs) sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC).MethodsPatients with aRCC with a clear cell component were stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk and randomised to NIVO (3 mg/kg) plus IPI (1 mg/kg) every three weeks ×4 doses, followed by NIVO (3 mg/kg) every two weeks; or SUN (50 mg) once per day ×4 weeks (6-week cycle). Efficacy endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) per independent radiology review committee in patients with intermediate/poor-risk disease (I/P; primary), intent-to-treat patients (ITT; secondary) and in patients with favourable-risk disease (FAV; exploratory).ResultsOverall, 1096 patients were randomised (ITT: NIVO+IPI, n=550, SUN, n=546; I/P: NIVO+IPI, n=425, SUN, n=422; FAV: NIVO+IPI, n=125, SUN, n=124). After 4 years minimum follow-up, OS (HR; 95% CI) remained superior with NIVO+IPI vs SUN in ITT (0.69; 0.59 to 0.81) and I/P patients (0.65; 0.54 to 0.78). Four-year PFS probabilities were 31.0% vs 17.3% (ITT) and 32.7% vs 12.3% (I/P), with NIVO+IPI vs SUN. ORR remained higher with NIVO+IPI vs SUN in ITT (39.1% vs 32.4%) and I/P (41.9% vs 26.8%) patients. In FAV patients, the HRs (95% CI) for OS and PFS were 0.93 (0.62 to 1.40) and 1.84 (1.29 to 2.62); ORR was lower with NIVO+IPI vs SUN. However, more patients in all risk groups achieved complete responses with NIVO+IPI: ITT (10.7% vs 2.6%), I/P (10.4% vs 1.4%) and FAV (12.0% vs 6.5%). Probability (95% CI) of response ≥4 years was higher with NIVO+IPI vs SUN (ITT, 59% (0.51 to 0.66) vs 30% (0.21 to 0.39); I/P, 59% (0.50 to 0.67) vs 24% (0.14 to 0.36); and FAV, 60% (0.41 to 0.75) vs 38% (0.22 to 0.54)) regardless of risk category. Safety remained favourable with NIVO+IPI vs SUN.ConclusionAfter long-term follow-up, NIVO+IPI continues to demonstrate durable efficacy benefits vs SUN, with manageable safety.Trial registration detailsClinicalTrials.gov identifier: NCT02231749.

Effectiveness of first-line immune checkpoint inhibitors (ICI) in advanced non-clear cell renal cell carcinoma (ccRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 316-316
Author(s):  
Jeffrey Graham ◽  
Connor Wells ◽  
Shaan Dudani ◽  
Chun Loo Gan ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
Cell Renal Cell Carcinoma

316 Background: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options in this setting. Data supporting the effectiveness of ICI based therapy in non-clear cell RCC (nccRCC) is more limited. Methods: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC). Patients with nccRCC were classified into 3 groups based on first-line therapy: ICI based therapy (in monotherapy or in combination), vascular endothelial growth factor targeted therapy (VEGF-TT) monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. Primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates. Results: We identified 1181 patients with nccRCC. In first-line, 78.2% received VEGF-TT, 15.8% mTOR inhibitors, and 5.5% ICI based therapy, of which 41.5% in monotherapy, 30.8% doublet-ICIs and 27.7% an ICI combined with VEGF-TT. Median OS in the ICI group was 28.6 months, compared to 19.2 and 12.6 in the VEGF-TT and mTOR groups, respectively. Median TTF was 6.9 months vs. 5.1 and 3.9 and ORR was 25% vs. 17.8% and 5.8% in the ICI, VEGF-TT and mTOR groups, respectively. After adjusting for IMDC risk group, histological subtype, and age, the hazard ratio (HR) for OS was 0.58 (95% CI 0.35-0.94, p=0.03) for ICI vs. VEGF-TT and 0.48 (95% CI 0.29-0.80, p=0.005) for ICI vs. mTOR. Conclusions: In advanced nccRCC, first-line ICI based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results need to be confirmed in prospective randomized trials. [Table: see text]

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