Poster Discussion Session Genitourinary Cancer—Kidney and Bladder
Available Starting on Friday, June 4, 2021; 9:00 EDT
4509 Nivolumab plus cabozantinib in patients with non-clear cell renal cell carcinoma: Results of a phase 2 trial. C-H Lee, MH Voss, MI Carlo, et al
- In this phase II trial, patients with papillary-, unclassified-, or translocation-associated RCC (cohort 1) or chromophobe RCC (cohort 2) were treated with cabozantinib 40 mg/day plus nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. Patients in cohort 1 demonstrated an ORR of 48%, a median PFS of 12.5 months, and a median OS of 28 months. No new grade 3/4 adverse events were reported. Cohort 2 was closed early due to lack of efficacy.
- Cabozantinib plus nivolumab was tolerated and effective in papillary-, unclassified-, or translocation-associated RCC patients; limited activity was observed in chromophobe RCC patients.
4513 First results of a randomized phase IB study comparing nivolumab/ ipilimumab with or without CBM-588 in patients with metastatic renal cell carcinoma. LA Meza, N Dizman, PG Bergerot, et al
- In this first report from a phase Ib study, confirmed clear cell and/or sarcomatoid metastatic RCC patients were treated with nivolumab plus ipilimumab with or without the probiotic CBM-588. Metagenomic sequencing of paired stool specimens revealed an eightfold increase in B. bifidum and a sixfold increase in B. adolescentis in both treatment groups from baseline to week 12. C. butyricum was detected in patients treated with CBM-588 only; pathogenic species were detected in nivolumab plus ipilimumab–treated patients only. The addition of CBM-588 improved the response rate (59% vs 11%) and median progression-free survival PFS (NR vs 11 weeks); CBM-588 did not impact toxicity.
- This prospective study marks the first report of enhancement of immune checkpoint inhibitor activity using a live bacterial product.
4515 Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and brain metastases: results from the CheckMate 920 trial. H Emamekhoo, MR Olsen, BC Carthon, et al
- In this phase IIIb/IV follow-up of the CheckMate 920 study, nivolumab plus ipilimumab continued to be well-tolerated by previously untreated patients with advanced/metastatic RCC with asymptomatic brain metastases. The objective response rate was 32%, with 8 patients achieving partial response and 10 achieving stable disease; median progression-free survival was 9 months. Overall survival was not reached at the time of this reporting.
- Long-term follow-up reveals good tolerance for and efficacy of this treatment in previously untreated patients with advanced/metastatic advanced RCC.
Poster Session: Genitourinary Cancer—Kidney and Bladder
Available Starting on Friday, June 4, 2021; 9:00 EDT
4546 TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC). E Verzoni, B Escudier, TE Hutson, et al
- In the phase III TIVO-3 study, investigators compared the survival benefit associated with tivozanib versus sorafenib among 350 patients with metastatic renal cell carcinoma (mRCC) who had failed two or three prior systemic regimens. The objective treatment response rate was higher for patients treated with tivozanib than for patients treated with sorafenib (23% vs 11%), and the duration of response was longer with tivozanib than with sorafenib (median duration in months, 20.3 vs 9.0). However, overall survival did not differ significantly between the patient groups.
- In a setting of third- and fourth-line treatment for mRCC, tivozanib resulted in better progression-free survival, a higher objective response rate, and more durable responses compared with sorafenib, but not in improved overall survival.
4552 The impact of antibiotic (Ab) exposure on clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT). MS Ernst, SA Alaiwi, N Dizman, et al
- The study authors evaluated the effect of recent antibiotic use on clinical outcomes in patients receiving immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT) for treatment of metastatic renal cell carcinoma (mRCC). Recent exposure to antibiotics was defined as use within 60 days before initiation of systemic therapy. In the ICI subgroup, exposed patients had significantly poorer IMDC disease risk compared with unexposed patients (favorable, 14% vs 18%; intermediate, 47% vs 62%; poor, 39% vs 21%; P = .03). A similar trend was observed in the VEGF-TT subgroup. However, on multivariate analysis overall survival did not vary significantly by antibiotic exposure status in either treatment subgroup.
- Among patients receiving ICI or VEGF-TT for mRCC, recent antibiotic use was significantly associated with a poorer IMDC risk category on univariate analysis but was not associated with overall survival after adjustment for confounding factors.
4553 Nivolumab plus cabozantinib (N+C) versus sunitinib (S) for advanced renal cell carcinoma (aRCC): Outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial. AB Apolo, T Powles, M Burotto, et al
- In the phase III CheckMate 9ER trial, patients were randomly assigned to receive nivolumab plus cabozantinib or sunitinib for treatment of advanced renal cell carcinoma. Outcomes were assessed within patient subgroups defined by several factors, including risk level. A clinical benefit of nivolumab plus cabozantinib for complete response and overall survival was observed in most patient subgroups. Objective response rates were higher for nivolumab plus cabozantinib (38%–66%) than for sunitinib (10%–44%) across most patient subgroups.
- Study findings support the clinical benefit of nivolumab plus cabozantinib over sunitinib for first-line treatment of advanced RCC in most patient subgroups.
4554 Outcomes of first-line (1L) ipilimumab and nivolumab (IPI-NIVO) and subsequent therapy in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC). CL Gan, JC Wells, AL Schmidt, et al
- Using data from the IMDC, these authors evaluated clinical outcomes among 706 patients with metastatic renal cell carcinoma (mRCC; mean age, 61 years) on first-line treatment with ipilimumab and nivolumab. Patients categorized by the IMDC criteria as having favorable risk had better 12-month overall survival rates (92%) than patients categorized as intermediate (79%) or poor risk (56%; P < .01). A similar trend was observed for 24-month overall survival. Overall, 66% of patients discontinued first-line treatment; most of these patients (55%) started second-line therapy with sunitinib, cabozantinib, pazopanib, or axitinib.
- In a real-world setting, IMDC risk criteria are predictive of clinical outcomes in patients receiving first-line ipilimumab and nivolumab for treatment of mRCC.
4555 Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). R Srinivasan, F Donskov, O Iliopoulos, et al
- In the phase II MK-6482 trial, 61 adults with measurable and localized/nonmetastatic clear-cell renal cell carcinoma (ccRCC) associated with germline von Hippel–Lindau (VHL) alterations were treated with belzutifan. After a median follow-up of 69 weeks, 22 patients (36%) had an objective response; the median time to response was 31 weeks, and the median duration of response was not reached. At week 52 of follow-up, the progression-free survival rate was 98%. Treatment-related adverse events were reported in 98% of patients, and 13% of patients had a grade 3 event. Outcomes in patients with non-RCC tumors were also evaluated. The objective response rate was 80% in patients with pancreatic neuroendocrine tumors and 32% in patients with CNS hemangioblastomas.
- Belzutifan provided a clinical benefit alongside a good safety profile for patients with VHL-associated ccRCC tumors, pancreatic neuroendocrine tumors, and hemangioblastomas.
4557 Treatment outcomes in renal cell carcinoma patients with metastases to the pancreas and other sites. C Duarte, B Beuselinck, N Weise, et al
- Study authors retrospectively evaluated clinical outcomes in 229 patients with metastatic renal cell carcinoma (mRCC) involving the pancreas. After a median follow-up of 51.5 months, the median overall survival after diagnosis of metastatic disease was 7.7 years. In unadjusted analysis, survival was significantly longer for patients who received first-line immunotherapy (median OS not reached) compared with patients who received first-line VEGF inhibitors (median OS, 7.6 years).
- The study findings support previous reports of longer survival among mRCC patients with involvement of the pancreas compared with other mRCC populations. First-line immunotherapy may enhance survival compared with other treatment options.
4560 Analysis of the CLEAR study in patients (pts) with advanced renal cell carcinoma (RCC): Depth of response and efficacy for selected subgroups in the lenvatinib (LEN) + pembrolizumab (PEMBRO) and sunitinib (SUN) treatment arms. V Grünwald, T Powles, E Kopyltsov, et al
- Study investigators used data from the phase III CLEAR study to evaluate outcomes in patients with advanced renal cell carcinoma (RCC). Patients were randomly assigned to receive lenvatinib plus pembrolizumab (LEN + PEMBRO; n = 355) or sunitinib (SUN; n = 357). Among patients categorized as intermediate- or poor-risk (per IMDC criteria), progression-free survival was significantly better in those who received LEN + PEMBRO compared with those who received SUN (median PFS, 22.1 vs 5.9 months; HR, 0.36). Similar trends were observed for progression-free survival among patients in the IMDC favorable-risk subgroup, for overall survival in all IMDC risk subgroups, and for ORR in all IMDC risk subgroups. The clinical benefit of LEN+PEMBRO was also observed in patients with target kidney lesions.
- Compared with SUN, LEN+PEMBRO improved survival among patients with advanced RCC, including patients with target kidney lesions.
4567 Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the phase 3 TIVO-3 study of relapsed or refractory mRCC. SK Pal, DF McDermott, B Escudier, et al
- This is a temporal analysis of safety outcomes in TIVO-3, a phase III study that randomly assigned patients with relapsed/refractory mRCC to tivozanib (TIVO; n = 173) or sorafenib (SOR; n = 170). Compared with SOR, TIVO was associated with fewer treatment-emergent adverse events (TEAEs) of grade >3 for diarrhea, rash, and PPE, and more TEAEs of grade >3 for hypertension; however, time to onset and duration of these TEAEs was similar across the treatments. Overall, compared with SOR, TIVO was associated with fewer dose reductions, interruptions, and discontinuations, as well as a longer time to onset of first dose reduction (45 vs 85 days), interruption (50 vs 81 days), and discontinuation (49 vs 114 days).
- In a setting of treatment for mRCC, the time to onset and duration of TEAEs were similar for TIVO and SOR, but dose modifications were less frequent and occurred after a longer interval for TIVO.
4578 Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC). BA McGregor, DM Geynisman, M Burotto, et al
- Using data from several trials, study authors compared nivolumab plus cabozantinib (N+C) with pembrolizumab plus axitinib (P+A) for first-line treatment of advanced renal cell carcinoma (aRCC). Matching of patient data was conducted using demographic and clinicopathologic factors, including IMDC risk score. In matched analysis, progression-free survival was longer in patients who received N+C compared with those who received P+A (median months, 19.3 vs 15.7). Compared with P+A, N+C was associated with a reduced risk of progression or death (HR, 0.70; P = .02), a higher ORR (difference, 8.4%; P = .11), and a longer duration of response (HR, 0.70; P = 0.36).
- Findings of this analysis, which adjusted for between-trial differences, suggest that N+C has a survival benefit compared with P+A for first-line treatment of aRCC.
Oral Abstract Session: Genitourinary Cancer—Kidney and Bladder
Monday, June 7, 2021; 8:00 AM–11:00 AM EDT
4500 Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426. BI Rini, ER Plimack, V Stus, et al
- In this phase III trial, follow-up from KEYNOTE-426, treatment-naïve patients with advanced clear cell RCC who received pembrolizumab plus axitinib continued to demonstrate improved overall survival (45.7 vs 40.1 months), progression-free survival (15.7 vs 11.1 months), and ORR (60.4% vs 39.5%) compared with patients on sunitinib monotherapy.
- At 42.8-months, the longest follow-up reported for anti–PD-1/L1 plus VEGF/VEGFR inhibitor combination therapy for first-line RCC, these study data continue to support the superior efficacy of pembrolizumab plus axitinib over sunitinib.
4501 CANTATA: Primary analysis of a global, randomized, placebo (Pbo)-controlled, double-blind trial of telaglenastat (CB-839) + cabozantinib versus Pbo + cabozantinib in advanced/metastatic renal cell carcinoma (mRCC) patients (pts) who progressed on immune checkpoint inhibitor (ICI) or anti-angiogenic therapies. NM Tannir, N Agarwal, C Porta, et al
- The phase II CANTANA study compared telaglenastat plus cabozantinib (Tela+Cabo) with placebo plus Cabo (Pbo+Cabo) among 444 patients with advanced/metastatic renal cell carcinoma (mRCC) who had previously received one to two lines of systemic therapy. After a median follow-up of 11.7 months, the Tela+Cabo and Pbo+Cabo arms were similar with regard to progression-free survival (median months, 9.2 vs 9.3) and ORR (31% vs 28%). Among patients with prior ICI treatment, Tela+Cabo was associated with longer progression-free survival than Pbo+Cabo (median months, 11.1 vs 9.2), but this trend was not significant. The treatment arms had similar rates of adverse events.
- Among patients with mRCC previously treated with systemic therapy, the addition of Tela to Cabo did not lead to improved patient outcomes.
4502 Health-related quality-of-life (HRQoL) analysis from the phase 3 CLEAR trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) for patients (pts) with advanced renal cell carcinoma (aRCC). RJ. Motzer, C Porta, B Alekseev, et al
- In this phase III secondary objective report from the CLEAR trial, the health-related quality of life of advanced RCC patients treated with lenvatinib plus pembrolizumab or lenvatinib plus everolimus was compared with that of those patients treated with sunitinib.
- In regard to patient-reported physical function, fatigue, dyspnea, pain, appetite loss, and diarrhea, adverse events in patients treated with lenvatinib plus pembrolizumab were similar or improved compared with those experiences by sunitinib-treated patients.
4507 A randomized phase II study comparing cisplatin and gemcitabine with or without berzosertib in patients with advanced urothelial carcinoma. SK Pal, A Mortazavi, MI Milowsky, et al
- In this phase II study, patients with advanced urothelial carcinoma were randomly assigned to receive cisplatin with gemcitabine (CG; n = 41) or CG plus berzosertib (CG + berzosertib; n = 46). Patients in the CG arm and those in the CG + berzosertib arm had similar response rates (54% vs 63%; P = .66) and progression-free survival (median months, 8.0 in both arms). Overall survival was longer in the CG arm compared with the CG + berzosertib arm (median months, 19.8 vs 14.4), but this finding was not significant. The CG + berzosertib arm had a higher proportion of patients with toxicity-related discontinuation compared with the CG arm (24% vs 15%).
- The addition of berzosertib did not improve the efficacy of CG for treatment of advanced urothelial carcinoma. Rather, it was associated with a nonsignificant trend toward worse survival and more drug toxicity.