Estimating the Impact of Adjuvant Treatment With Nivolumab on Long-Term Survivorship Rates Compared With Surveillance in Muscle Invasive Urothelial Carcinoma: Mixture Cure Modeling Analyses of Disease-Free Survival From the Phase 3 CheckMate 274 Trial.

528 Background: Durable DFS and cure are the ultimate goals for the treatment of muscle invasive urothelial carcinoma (MIUC) with radical cystectomy. This analysis employed mixture cure models (MCMs) to estimate the underlying cure fraction among high-risk MIUC patients following radical resection in the Phase 3 CheckMate-274 study. Methods: MCMs were applied to patient-level DFS data from the trial (minimum follow-up: 31.6 months). Intention-to-treat (ITT) population and the subpopulation with tumor PD-L1 expression ≥1% were analyzed separately for nivolumab (NIVO) and placebo (PBO) arms. In MCMs, the patient populations were assumed to consist of two exclusive subgroups as cured and uncured. Cured subgroup was assumed to be free of disease recurrence and disease-related mortality risks. The uncured subgroup was at the risk of both disease recurrence and all-cause mortality. DFS for the cured subgroup was estimated using background mortality rates published by WHO matched to the trial’s demographic characteristics. DFS for the uncured subgroup was modelled using parametric distributions, which were characterized along with the cure fraction by maximum likelihood methods. Model selection was primarily based on clinical plausibility of estimated DFS for the uncured subgroup. Visual comparison of the fits from the MCMs to the reported DFS data from the trial and goodness-of-fit statistics also assisted model selection. Results: In the trial, 353 patients were treated with NIVO (mean age: 65.3; male: 75.1%; PD-L1≥1%: 39.7%) and 356 patients were in PBO control (mean age: 65.9; male: 77.2%; PD-L1≥1%: 39.9%). Selected models estimated almost all uncured patients to experience recurrence within 5 years. The estimated cure fraction in the ITT population ranged from 43.1%-45.1% in the NIVO arm (95% CI: 36.7%-51.6%), and 36.4%-37.0% in the PBO arm, (95% CI: 30.9%-43.0%) for clinically plausible models. Projected range of 10-year mean DFS for the ITT patients was 4.38-4.47 years in the NIVO arm and 3.61-3.64 years in the PBO arm. Estimated cure fractions in the PD-L1≥1% subpopulation ranged from 59.1%-61.0% in the NIVO arm (95% CI: 48.9%-72.0%), and 35.9%-36.9% in the PBO arm, (95% CI: 27.5%-45.9%). Projected range of 10-year mean DFS for the PD-L1≥1% subpopulation was 5.54-5.65 years in the NIVO arm and 3.54-3.57 years in the PBO arm. Conclusions: In the adjuvant treatment of MIUC, relative to radical resection only, systemic therapy with NIVO is associated with a 6-9 percentage points higher cure fraction in the ITT population. Tumor PD-L1≥1% expression was associated with higher cure fractions in the NIVO arm but had only negligible impact on the underlying cure fraction in the PBO arm. Clinical trial information: NCT02632409 .

658 Background: In the phase 3, randomized, double-blind CheckMate 274 trial, adjuvant NIVO demonstrated statistically significant and clinically meaningful disease-free survival (DFS) benefit vs PBO in pts with high-risk MIUC after radical surgery (RS) ± prior neoadjuvant cisplatin-based chemotherapy (NAC). With extended 3-y median follow-up, continued improvements in DFS were seen with NIVO vs PBO in the primary efficacy populations (intent-to-treat [ITT], tumor programmed death ligand 1 [PD-L1] expression ≥ 1%) and in pts with MIBC. Early trends in interim OS favored NIVO vs PBO in ITT and tumor PD-L1 ≥ 1% pts. Here we report additional efficacy outcomes for pts with MIBC. Methods: Pts were randomized 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 y of adjuvant treatment, stratified by tumor PD-L1 expression, nodal status, and prior NAC. Primary endpoints were DFS in ITT and tumor PD-L1 expression ≥ 1% pts. OS in ITT and PD-L1 ≥ 1% pts was a secondary endpoint. Analysis of MIBC pts was exploratory. MIBC OS data are from preplanned interim analyses of ITT and PD-L1 ≥ 1% pts. OS follow-up is ongoing as the prespecified statistical boundaries for significance in ITT and PD-L1 ≥ 1% pts were not crossed at the time of these analyses. Results: Of 709 randomized pts (ITT), 560 (79%) had MIBC (NIVO, n = 279; PBO, n = 281); 284 (51%) of MIBC pts had prior NAC. With median follow-up of 36.1 mo (ITT), DFS improvement with NIVO vs PBO was consistent between all pts with MIBC (hazard ratio [HR] 0.63) and those with (HR 0.58) and without prior NAC (HR 0.69; Table). For OS, HRs favored NIVO vs PBO in all pts with MIBC (HR 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR 0.48), as well as in pts with MIBC with (HR 0.74) and without prior NAC (HR 0.67). Safety was consistent with previous data in ITT pts; no new safety signals were identified. Conclusions: With 3-y median follow-up, consistent benefit in DFS was observed with NIVO vs PBO in all MIBC pts and across prior NAC subgroups. The HR for OS favored NIVO in all MIBC pts, in those with PD-L1 ≥ 1%, and regardless of prior NAC status. These results continue to support adjuvant NIVO as a standard of care for high-risk MIUC and MIBC, potentially providing an opportunity for a curative outcome. Clinical trial information: NCT02632409 . NIVOn NIVOMedian(95% CI), mo PBOn PBOMedian(95% CI), mo HR (95% CI) DFS All MIBC 279 25.6 (19.2–41.8) 281 8.5 (7.3–13.7) 0.63 (0.51–0.78) With prior NAC 142 19.6 (15.6–48.2) 142 8.3 (5.6–11.2) 0.58 (0.43–0.79) No prior NAC 137 25.9 (19.2–51.5) 139 13.7 (7.8–22.1) 0.69 (0.50–0.94) OS All MIBC 279 NR (45.0–NE) 281 39.9 (29.8–52.1) 0.70 (0.55–0.90) PD-L1 ≥ 1% 113 NR (NE–NE) 117 37.6 (26.9–NE) 0.48 (0.29–0.77) With prior NAC 142 55.2 (41.8–NE) 142 40.2 (28.8–53.7) 0.74 (0.53–1.03) No prior NAC 137 NR (40.7–NE) 139 37.7 (28.7–65.2) 0.67 (0.47–0.95) NE, not estimable; NR, not reached.

391 Background: The standard of care (SOC) for patients (pts) with MIUC is radical surgery ± cisplatin-based neoadjuvant chemotherapy (chemo), but many pts are cisplatin-ineligible. There is no conclusive evidence supporting adjuvant chemo in pts who did not receive neoadjuvant chemo and in those with residual disease after neoadjuvant cisplatin. This phase 3 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in pts with MIUC after radical surgery ± neoadjuvant cisplatin (CheckMate 274) aims to address an unmet need in these pts. We report the initial results. Methods: This is a phase 3, randomized, double-blind, multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis) after radical surgery. Pts were randomized 1:1 to NIVO 240 mg Q2W or PBO for ≤ 1 year of adjuvant treatment. Pts had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemo, evidence of UC at high risk of recurrence per pathologic staging, were disease-free by imaging, and ECOG PS ≤ 1. Primary endpoints: disease-free survival (DFS) in all randomized pts (ITT population) and in pts with tumor PD-L1 expression ≥ 1%. DFS was stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. Non–urothelial tract recurrence-free survival (NUTRFS) in ITT pts and in pts with PD-L ≥ 1% is a secondary endpoint. Safety is an exploratory endpoint. Results: In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO; 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. DFS and NUTRFS were improved with NIVO vs PBO in both populations (Table). DFS improvement with NIVO was generally consistent across subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of pts in the NIVO and PBO arms, respectively. Conclusions: NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%. AEs were manageable and consistent with previous reports. These results support adjuvant NIVO as a new SOC for pts with MIUC with high risk for recurrence despite neoadjuvant chemo or those ineligible for and/or declining cisplatin-based chemo. Clinical trial information: NCT02632409 . Research Sponsor: Bristol Myers Squibb[Table: see text]

LBA443 Background: The 2 primary endpoints of the CheckMate 274 trial were met as nivolumab (NIVO) improved disease-free survival (DFS) versus placebo (PBO) in the intent-to-treat (ITT) population and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. We report extended follow-up data. Methods: CheckMate 274 is a phase 3, double-blind trial of adjuvant NIVO versus PBO for high-risk muscle-invasive urothelial carcinoma (MIUC) (bladder, ureter, or renal pelvis) after radical resection. Patients were randomly assigned 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 year of treatment. Patients had pathologic evidence of UC at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. Primary endpoints were DFS in ITT patients and in patients with PD-L1 ≥ 1%. DFS was also analyzed in prespecified subgroups. Overall survival and non–urothelial tract recurrence-free survival (NUTRFS) in ITT patients and in patients with PD-L1 ≥ 1% were secondary endpoints. Distant metastasis-free survival (DMFS) and safety were exploratory endpoints. Results: There were 353 patients randomly assigned to NIVO (PD-L1 ≥ 1%, n = 140) and 356 to PBO (PD-L1 ≥ 1%, n = 142). With median follow-up of 36.1 months (minimum follow-up, 31.6 months), median DFS was 22.0 months with NIVO versus 10.9 months with PBO in ITT patients and 52.6 months with NIVO versus 8.4 months with PBO in patients with PD-L1 ≥ 1% (Table). DFS benefit was seen in most subgroups analyzed including age, sex, ECOG PS, nodal status, prior cisplatin-based chemotherapy, and PD-L1 status. NUTRFS and DMFS benefits with NIVO versus PBO were also observed in both populations (Table). Grade 3–4 treatment-related adverse events occurred in 18.2% and 7.2% of patients in the NIVO and PBO arms, consistent with the primary analysis. Overall survival will be assessed at a future database lock. Conclusions: With extended follow-up, NIVO continued to show DFS, NUTRFS, and DMFS benefits versus PBO. The hazard ratio (HR) for DFS and NUTRFS in PD-L1 ≥ 1% patients and for DMFS in both ITT and PD-L1 ≥ 1% patients also continued to improve versus the primary analysis. No new safety signals were identified. These results further support adjuvant NIVO as a standard of care for high-risk MIUC after radical resection. Clinical trial information: NCT02632409 . [Table: see text]

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

4585 Background: In the CheckMate 274 trial, disease-free survival (DFS) was significantly improved with nivolumab (NIVO) vs placebo (PBO) both in intent-to-treat (ITT) patients (pts) (hazard ratio [HR], 0.70; 98.22% confidence interval [CI], 0.55–0.90; P < 0.001) and in pts with tumor programmed death ligand 1 (PD-L1) expression ≥ 1% (HR, 0.55; 98.72% CI, 0.35–0.85; P < 0.001). We report results for the subgroup of pts with bladder cancer, the most predominant type of urothelial carcinoma. Methods: CheckMate 274 is a phase 3, randomized, double-blind trial of adjuvant NIVO vs PBO in high-risk muscle-invasive urothelial carcinoma (bladder, ureter, renal pelvis) after radical resection. Pts were randomized 1:1 to NIVO 240 mg intravenously every 2 weeks or PBO for ≤ 1 year of adjuvant treatment and stratified by nodal status, prior neoadjuvant cisplatin, and tumor PD-L1 expression. Pts had radical resection ± neoadjuvant chemotherapy and were at high risk of recurrence on final pathologic staging. Primary endpoints were DFS in ITT pts and in pts with PD-L1 ≥ 1%. Non–urothelial tract recurrence-free survival (NUTRFS) was a secondary endpoint, and distant metastasis-free survival (DMFS) was an exploratory endpoint. This exploratory analysis focused on the subgroup of pts with muscle-invasive bladder cancer (MIBC) after radical resection. Results: Of 709 randomized pts in the trial, 560 had MIBC (NIVO, n = 279; PBO, n = 281). With a minimum follow-up of 11.0 months, a DFS benefit was observed with NIVO vs PBO in these pts, regardless of tumor PD-L1 expression (Table). DFS probability at 12 months in all MIBC pts was 66% with NIVO and 45% with PBO. DFS was improved with NIVO vs PBO across subgroups according to age, sex, ECOG performance status, nodal status, and PD-L1 expression status. Improvement in NUTRFS and DMFS with NIVO vs PBO was also observed (Table). Grade 3–4 treatment-related adverse events occurred in 17% and 6% of pts in the NIVO and PBO arms, respectively. Conclusions: Improvement in DFS was observed with NIVO over PBO in pts with MIBC after radical resection regardless of tumor PD-L1 expression. The DFS benefit was observed in all prespecified subgroups. These results further support adjuvant NIVO as a standard-of-care treatment for pts with high-risk MIBC after radical resection ± neoadjuvant cisplatin-based chemotherapy. Clinical trial information: NCT02632409. [Table: see text]

LBA02-08 RESULTS FROM THE EXTENDED FOLLOW-UP IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER IN THE CHeckMATE 274 TRIAL

1737MO Tumor and immune features associated with disease-free survival with adjuvant nivolumab in the phase III CheckMate 274 trial

Introduction: CheckMate 914 (CM-914) Part A is a double-blind, phase III randomized trial of the Nivolumab (NIVO) plus Ipilimumab (IPI) vs placebo (PBO) in localized ccRCC. Our prior report from this study suggested a disease-free survival (DFS) benefit for NIVO+IPI among patients with Fuhrman grade 4, TNM stages PT2a and PT4, or sarcomatoid features, although the sample size was limited. It is known that high circulating KIM-1 is associated with worse DFS after nephrectomy. In this exploratory post hoc analysis, we investigated whether high KIM-1 may help identify a subset of patients who benefit from adjuvant NIVO+IPI. Methods: Patients (n=816) with RCC after nephrectomy were randomized in CM-914 Part A to receive NIVO+IPI or PBO as previously described. Assessment of KIM-1 levels was performed using enzyme linked immunoassay (ELISA) on pre-treatment (n=584) and matched on-treatment blood samples (n=584). We used pre-treatment tumor samples to assess PD-L1% tumor cell expression (%TC) in an PD-L1 IHC 28-8 pharm Dx assay. The association between biomarkers and DFS outcomes was investigated by Kaplan-Meier (KM) and Cox proportional hazards analysis. Results: Median baseline serum KIM-1 level was 102 (9.9 - 1055.7) pg/mL. Serum KIM-1 levels were higher in males vs females, ≥65 yrs vs <65 yrs, Asian vs white patients, and patients with partial vs radical nephrectomy. In the PBO arm, subjects with highest quartile of pre-treatment KIM-1 had significantly worse DFS than those from the three lower quartiles. In contrast, this DFS risk among the subjects within the highest KIM-1 quartile was mitigated with NIVO+IPI treatment. Among patients within the highest quartile of pre-treatment KIM-1, there was trend for better DFS for NIVO+IPI versus PBO, HR=0.6 (0.34-1.04). Increase in KIM-1 during study therapy was positively associated with higher DFS rate in both arms. Multivariable analysis showed that PD-L1 %TC was predictive at predefined PD-L1 cutoffs (>=1%, >=5%, and >=10%), associating with improved DFS compared to placebo. Subjects with high PD-L1 expression had a DFS benefit from NIVO+IPI independent of KIM-1. Conclusion: Circulating KIM-1 and tumor PD-L1 expression may enrich for benefit from IO therapy in adjuvant ccRCC and hence holds promise for informing risk stratification and patient inclusion in neoadjuvant or adjuvant clinical trials. Citation Format: Sai Vikram Vemula, Wenxin Xu, Yu Wang, Xiaowen Liu, Jorge Ruiz de Somocurcio, David McDermott, Jun Li, Rupal Bhatt, Chung-Wei Lee, Burcin Simsek, Saurabh Gupta, Robert Motzer. High serum kidney injury marker-1 and high baseline tumor PD-L1 protein expression levels are independently associated with treatment effect in adjuvant nivolumab plus ipilimumab vs placebo in localized clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5151.

PD10-01 DISEASE-FREE SURVIVAL WITH LONGER FOLLOW-UP FROM THE CHECKMATE 274 TRIAL OF ADJUVANT NIVOLUMAB IN PATIENTS AFTER SURGERY FOR HIGH-RISK MUSCLE-INVASIVE UROTHELIAL CARCINOMA

Nivolumab is a standard-of-care adjuvant therapy for patients with muscle-invasive urothelial carcinoma (MIUC) at high risk for recurrence after radical resection. However, a better understanding of its use and clinical effectiveness in general patient populations is needed. To examine treatment patterns and clinical outcomes for patients with MIUC treated with adjuvant nivolumab in a community setting. This nationwide retrospective medical record review cohort study included patients with clinical stage II to IIIB MIUC who initiated adjuvant nivolumab between September 1, 2021, and November 30, 2022, with at least 6 months follow-up (unless deceased in <6 months). Managing physicians from the Cardinal Health Oncology Provider Extended Network abstracted patient data from electronic records. Diagnosis of MIUC and receipt of adjuvant nivolumab. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Data from 253 patients were included in this study, with median (IQR) follow-up from adjuvant nivolumab initiation of 12.8 (9.6-15.4) months. The median (IQR) age at MIUC diagnosis was 67.8 (61.5-72.4) years, and most patients were male (169 patients [66.8%]). Overall, 141 patients (55.7%) had received neoadjuvant chemotherapy (NAC). During adjuvant nivolumab, 52 patients (20.6%) experienced an adverse event (AE). At last follow-up, the median (IQR) duration of adjuvant nivolumab was 11.2 (8.4-12.0) months, and 220 patients (87.0%) had discontinued treatment. Discontinuation was primarily due to completion of scheduled therapy duration (163 of 220 patients [74.1%]), while 10 of 220 patients (4.5%) discontinued due to AEs. Median DFS and OS were not reached, and estimates at 12 months after initiation were 86.3% (95% CI, 81.0%-90.2%) for DFS and 90.8% (95% CI, 86.0%-94.0%) for OS. Outcomes were similar in patients who did not receive NAC. At last follow-up, 226 patients (89.3%) were alive, of whom 209 (92.5%) were disease-free. This retrospective medical record review cohort study of patients with MIUC found clinical outcomes consistent with those observed in the CheckMate 274 trial. These results support the use of adjuvant nivolumab for patient populations in the community, including patients who did not receive NAC. Further research with extended follow-up is needed to elucidate long-term clinical outcomes of adjuvant nivolumab.

491 Background: CheckMate 274 demonstrated a significant improvement in disease-free survival (DFS) with nivolumab (NIVO) versus placebo (PBO) both in the intent-to-treat population (hazard ratio [HR], 0.70; 98.22% confidence interval [CI], 0.55–0.90; P &lt; 0.001) and in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1% assessed by the tumor proportion score (TPS) (HR, 0.55; 98.72% CI, 0.35–0.85; P &lt; 0.001). An exploratory subgroup analysis showed a trend toward a DFS benefit with NIVO in pts with TPS &lt; 1% (0.82; 95% CI, 0.63–1.06). To further characterize the relationship between PD-L1 expression and NIVO efficacy, we report an analysis of DFS based on PD-L1 expression in both tumor and immune cells using the combined positive score (CPS). Methods: CheckMate 274 is a phase 3, randomized, double-blind, multicenter trial of NIVO versus PBO in pts with high-risk muscle-invasive urothelial carcinoma after radical surgery. Pts were randomized 1:1 to NIVO 240 mg or PBO every 2 weeks intravenously for 1 year of adjuvant treatment. The primary endpoints of the study are DFS in the intent-to-treat population and in pts with TPS ≥ 1%. The Dako PD-L1 IHC 28-8 pharmDx assay was used to evaluate TPS. CPS was determined retrospectively from previously stained immunohistochemistry slides using the CPS algorithm. CPS was calculated as the number of both PD-L1 positive tumor and immune cells divided by the number of viable tumor cells in the evaluable tumor area, multiplied by 100; TPS was similarly calculated with the number of PD-L1 positive tumor cells as the numerator. This analysis only included pts with both quantifiable CPS and TPS. Results: Of the 629 pts with quantifiable TPS and CPS, 249 (40%) had TPS ≥ 1% (NIVO, n = 124; PBO, n = 125), 380 (60%) had TPS &lt; 1% (NIVO, n = 191; PBO, n = 189), 557 (89%) had CPS ≥ 1 (NIVO, n = 281; PBO, n = 276), and 72 (11%) had CPS &lt; 1 (NIVO, n = 34; PBO, n = 38). Within TPS &lt; 1% pts, 81% (n = 309) had CPS ≥ 1. The number of pts and the DFS outcomes in pts with TPS ≥ 1% and CPS ≥ 1 are shown in the Table. In pts with TPS &lt; 1% who also had CPS ≥ 1, median DFS (95% CI) was 19.2 (15.6–33.4) months with NIVO versus 10.1 (8.2–19.4) months with PBO. The HR for NIVO versus PBO in these pts was 0.73 (95% CI, 0.54–0.99). Conclusions: This exploratory analysis of PD-L1 expression by CPS showed a higher proportion of pts with CPS ≥ 1 than TPS ≥ 1%, and that most pts with TPS &lt; 1% had CPS ≥ 1. In the CPS ≥ 1 subgroup, median DFS with NIVO was more than double that with placebo. These results support the conclusion that pts with TPS &lt; 1% also benefit from adjuvant NIVO. Clinical trial information: NCT02632409. [Table: see text]

SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence. We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo. Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, -0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib. Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART.

LBA56 - Primary efficacy analysis results from the SORCE trial (RE05): Adjuvant sorafenib for renal cell carcinoma at intermediate or high risk of relapse: An international, randomised double-blind phase III trial led by the MRC CTU at UCL

Introduction: Lung cancer incidence in China has increased and it remains the leading cause of cancer death, highlighting a need for new treatments. We report results from CheckMate 078, the first phase 3 study of an anti-programmed death (ligand) 1 (PD-[L]1) agent in predominantly Chinese patients with NSCLC and disease progression after platinum (Pt)-based chemotherapy. Methods: Patients who had disease progression during or after Pt-based doublet chemotherapy were randomized 2:1 to receive nivolumab (3 mg/kg Q2W) or docetaxel (75 mg/m2 Q3W). Patients were included regardless of tumor histology or PD-L1 expression, and randomization was stratified according to both of these factors (≥1% vs &amp;lt;1%/unevaluable tumor PD-L1; squamous vs non-squamous histology). Patients with epidermal growth factor receptor mutation-positive tumors were excluded. The primary endpoint was overall survival (OS); other endpoints included progression-free survival (PFS) and objective response rate (ORR). Results: 639 patients were enrolled from December 2015 to December 2016; 504 were randomized. Of all randomized patients, ~90% were from China, 60% had non-squamous tumor histology; tumor PD-L1 expression was &amp;lt;1% in 41% of patients and ≥1% in 50% of patients (9% unevaluable). Minimum follow-up was 8.8 months. OS was significantly improved with nivolumab (n=338) vs docetaxel (n=166); median OS was 12.0 vs 9.6 months, respectively (hazard ratio [HR; 97.7% CI]: 0.68 [0.52, 0.90]; P&amp;lt;0.001). The HR (95% CI) for OS was 0.61 (0.42, 0.89) in patients with squamous NSCLC and 0.76 (0.56, 1.04) in patients with non-squamous NSCLC. In patients with tumor PD-L1 expression &amp;lt;1% and ≥1%, the HR (95% CI) was 0.75 (0.52, 1.09) and 0.62 (0.45, 0.87), respectively. Median PFS was 2.8 months in both treatment arms; PFS curves began to separate at 3 months, resulting in a PFS advantage with nivolumab (HR [95% CI]: 0.77 [0.62, 0.95]; P=0.0147). ORR was 17% with nivolumab vs 4% with docetaxel; median duration of response was not reached with nivolumab (95% CI: 11.1 months, not available [NA]) and 5.3 (95% CI: 3.58, NA) months with docetaxel. Rates of grade ≥3 treatment-related adverse events were lower among patients treated with nivolumab (10%) vs docetaxel (48%). Conclusions: In this population of patients with advanced NSCLC previously treated with Pt-based chemotherapy, nivolumab demonstrated superior OS, PFS, and ORR compared with docetaxel. Efficacy and safety of nivolumab in this first randomized controlled trial of nivolumab in NSCLC in a predominantly Chinese patient population were consistent with the results of the pivotal global CheckMate 017/057 studies. Citation Format: Yi-Long Wu, Shun Lu, Ying Cheng, Caicun Zhou, Jie Wang, Tony Mok, Li Zhang, Haiyan Tu, Lin Wu, Jifeng Feng, Yiping Zhang, Alexander Valeriercich Luft, Jianying Zhou, Zhiyong Ma, You Lu, Chengping Hu, Yuankai Shi, Christine Baudelet, Zoe Li, Jianhua Chang. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer (NSCLC): results of the phase 3 CheckMate 078 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT114.