Extended follow-up results from the CheckMate 274 trial.

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]

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 < 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 < 0.001). An exploratory subgroup analysis showed a trend toward a DFS benefit with NIVO in pts with TPS < 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 < 1% (NIVO, n = 191; PBO, n = 189), 557 (89%) had CPS ≥ 1 (NIVO, n = 281; PBO, n = 276), and 72 (11%) had CPS < 1 (NIVO, n = 34; PBO, n = 38). Within TPS < 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 < 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 < 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 < 1% also benefit from adjuvant NIVO. Clinical trial information: NCT02632409. [Table: see text]

Background. New potential biomarker for patients with metastatic hormone-naive prostate cancer (PCa) might be detection of programmed death ligand 1 (PD-L1) expression in tumor which is associated with worsened results of treatment and decreased survival in patients with pancreatic cancer, lung cancer and other malignant tumors. Objective : to evaluate the prognostic value of positive tumor PD-L1 status on time to castration resistance (CRPCa) in patients with meta­static PCa receiving hormonal androgen deprivation therapy in first-line systemic treatment. Materials and methods. A total of 35patients with metastatic hormone-naive PCa receiving androgen deprivation therapy with luteinizing hormone-releasing hormone analogue and follow-up at N.N. Blokhin National Medical Research Center of Oncology were recruited in our prospective study. Tumor features of all patients were evaluated for PD-L1 expression on tumor cells by immunohistochemical studies of paraffin block sections obtained under the visual control of the pathologist using a set of monoclonal anti-PD-L1 antibody (28-8) (ab 205921) and Ventana BenchMark GXSlide staining system. Tumor tissue was obtained before starting androgen deprivation therapy. The expression level of PD-L1 >1 % in tumor cells was taken for the positive tumor PD-L1(+) status. Results . Median follow-up was 32.8 months. Positive tumor PD-L1(+) status was identified in 10 (28.6 %) cases. Median time to CRPCa was significantly lower in patients with PD-L1(+) status, than in negative PD-L1(—) status (21.44 vs. 49.12, p = 0.006 log rank test). Multi­variate Cox regression analysis confirmed independence prognostic value of PD-L1(+) associated with decreased time to CRPCa (hazard ration 5.95, 95 % confidence interval 1.97—17.99; p = 0.002), including in subgroup of patients with low-volume metastatic disease (hazard ration 7.33, 95 % confidence interval 1.81—29.60; p = 0.005). Discussion . Interaction of PD-1 receptors and its ligands PD-L1/PD-L2 is the key mechanism causing tumor immune escape and progression of the cancer. There are discussed certain ways of inducing PD-L1 expression and its prognostic value on aggressive nonmetastatic PCa. High frequency of positive PD-L1 status was revealed in rare histological subtypes of PCa associated with unfavorable prognosis and visceral metastasis. Conclusion. The results of our study demonstrated the positive tumor PD-L1 status as an independent unfavorable prognostic factorfor patients with metastatic hormone-naive PCa associated with decreased time to castration resistance, including in patients with low volume metastatic disease.

LBA9025 Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI demonstrated long-term, durable survival benefit vs platinum-doublet chemo in patients (pts) with metastatic NSCLC regardless of tumor programmed death ligand 1 (PD-L1) expression level. Here we present the longest reported follow-up (5 y) of a phase 3 trial of 1L combination immunotherapy in metastatic NSCLC. Methods: Adults with previously untreated stage IV or recurrent NSCLC, no known EGFR/ ALK alterations , and an ECOG performance status ≤ 1 were enrolled and stratified by histology. Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity, or ≤ 2 y for immunotherapy. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and a novel efficacy endpoint, treatment-free interval. Treatment-free interval was measured in pts who discontinued study therapy (for any reason including treatment completion) and was defined as the time from last study dose to start of subsequent systemic therapy or death, whichever occurred first. Results: Minimum follow-up was 61.3 mo (database lock, Feb 15, 2022). In pts with tumor PD-L1 ≥ 1% (N = 1189), continued long-term OS benefit was seen with NIVO + IPI vs chemo (HR, 0.77 [95% CI, 0.66–0.91]); 5-y OS rates were 24% (NIVO + IPI), 17% (NIVO), and 14% (chemo). OS benefit also continued in pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR, 0.65 [95% CI, 0.52–0.81]); 5-y OS rates were 19% (NIVO + IPI), 10% (NIVO + chemo), and 7% (chemo). Clinical benefit with NIVO + IPI vs chemo was observed across additional efficacy endpoints in the overall population and in pts alive at 5 y (table). PFS, ORR, and DOR with NIVO and NIVO + chemo will be presented. Among pts alive at 5 y in the NIVO + IPI group, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) remained treatment-free ≥ 3 y after discontinuing study therapy; median (range) duration of NIVO ± IPI therapy was 17.7 (0-25.5) mo (PD-L1 ≥ 1%) and 9.5 (0-25.1) mo (PD-L1 < 1%). No new safety signals were observed. Conclusions: With a 5-y minimum follow-up, NIVO + IPI continues to provide long-term, durable clinical benefit vs chemo in previously untreated pts with metastatic NSCLC, regardless of PD-L1 expression. NIVO + IPI led to increased 5-y survivorship; the majority of these pts were treatment-free for ≥ 3 y post-treatment discontinuation. Clinical trial information: NCT02477826. [Table: see text]

The Prognostic Impact of PD-L1 and CD8 Expression in Anal Cancer Patients Treated with Chemoradiotherapy

BackgroundProgrammed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS).MethodsNinety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS.ResultsOf the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052.ConclusionsTumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.

Chemotherapy + PD-1/PD-L1 Blockade Should Be the Preferred Option in the Neoadjuvant Therapy of NSCLC

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

Introduction: Checkpoint inhibitors have demonstrated activity in brain lesions in several tumor types, including NSCLC. CheckMate 227 Part 1 (NCT02477826) met its two independent co-primary endpoints, including improved overall survival (OS) for NIVO + IPI vs histology-based chemotherapy (chemo) in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. Benefit was also observed in pts with PD-L1 &amp;lt; 1%. Eligible pts included those with treated, asymptomatic brain metastases (mets). Here we present a post-hoc analysis of efficacy and safety in pts with and without baseline (BL) brain mets. Methods: Eligible pts were chemo-naive, with stage IV or recurrent NSCLC, no known sensitizing EGFR/ALK alterations, and ECOG PS 0–1. Pts with treated brain mets who were asymptomatic for ≥ 2 wks prior to randomization were eligible; corticosteroids equivalent to ≤ 10 mg of prednisone daily were permitted if stable or decreasing for ≥ 2 wks prior to randomization. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo; pts with PD-L1 &amp;lt; 1% (n = 550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 360 mg Q3W + chemo, or chemo. Pts were treated until disease progression, unacceptable toxicity, or ≤ 2 y of immunotherapy. Results: BL characteristics were generally similar between pts with and without BL brain mets, except that a greater proportion of pts with BL brain mets were &amp;lt; 65 years of age and had non-squamous histology. Efficacy data are shown in the Table. Any-grade nervous system adverse events were reported in 46% of pts with BL brain mets treated with NIVO + IPI and 42% of those treated with chemo, most were grade 1–2. Conclusion: In this post-hoc analysis of pts with advanced NSCLC, NIVO + IPI appeared to provide similar benefit in pts with and without BL brain mets. No new safety signals were identified. Table.Efficacy by baseline brain metastases in CheckMate 227 Part 1Patients with baseline brain metastasesPatients without baseline brain metastasesNIVO + IPI (n = 69)Chemo (n = 66)NIVO + IPI (n = 514)Chemo (n = 517)OS, median (95% CI), mo18.8 (9.2-29.4)13.7 (10.5-16.2)17.1 (15.3-19.9)13.9 (11.8-15.3)HR (95% CI)0.57 (0.38-0.85)0.76 (0.66-0.88)1-y rates, %575962542-y rates, %44264030PFS,a median (95% CI), mo5.4 (3.1-8.6)5.8 (4.3-8.0)4.9 (4.1-5.7)5.4 (4.5-5.6)HR (95% CI)0.79 (0.52-1.19)0.81 (0.70-0.93)1-y rates, %382132172-y rates, %227206ORR,a %33263328DOR,a median (95% CI), mo24.9 (11.3-NR)8.4 (4.2-13.9)19.6 (15.5-28.6)5.8 (4.8-6.9)1-y rates, %724065262-y rates, %5384610Minimum follow-up was 29.3 mo.aPer BICR. BICR, blinded independent central review; CI, confidence interval; chemo, chemotherapy; DOR, duration of response; HR, hazard ratio; IPI, ipilimumab; mo, month; NIVO, nivolumab; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; y, year. Citation Format: Hossein Borghaei, Adam Pluzanski, Reyes Bernabe Caro, Mariano Provencio, Sjaak Burgers, Enric Carcereny, Keunchil Park, Aurelia Alexandru, Lorena Lupinacci, Randeep Sangha, Judith Raimbourg, Alain Vergnenegre, Konstantinos Syrigos, Fabrice Barlesi, Norbert Frickhofen, Ang Li, Ravi Kasinathan, Luis Paz-Ares. Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment for patients with advanced non-small cell lung cancer (NSCLC) with brain metastases: Results from CheckMate 227 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT221.

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 &lt; 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 &lt; 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 &lt; 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 &lt; 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

BackgroundSpatial patterns of CD8+ T cells in the tumor microenvironment are associated with clinical outcomes in patients with advanced solid tumors. However, attempts to quantify spatial topology are hindered by...

Background: The real-world survival outcomes of first-line (1L) immunotherapy (IO)-based regimens for the treatment of advanced non-small cell lung cancer (aNSCLC) were assessed utilizing the Flatiron Health database from January 2011 to June 2023. Methods: Adult patients (pts) with aNSCLC receiving 1L IO monotherapy or single-agent IO + chemotherapy on or after January 1, 2016, were identified. Pts were excluded if they had EGFR/ALK mutations or unknown histological type. Overall survival (OS) and real-world progression-free survival (rwPFS) of 1L IO monotherapy and IO + chemotherapy were described using Kaplan-Meier analyses. Results: A total of 14,320 pts were included (5,166 pts receiving IO monotherapy; 9,154 pts receiving IO + chemotherapy). Among pts receiving IO monotherapy, the 1-, 2-, 3-, and 4-year OS rates were 52.3%, 36.5%, 27.4%, and 21.9%, respectively. The corresponding rwPFS rates were 29.2%, 17.5%, 12.7%, and 9.2%. Among pts receiving IO + chemotherapy, the 1-, 2-, 3-, and 4-year OS rates were 50.7%, 32.6%, 23.9%, and 19.2%. The corresponding rwPFS rates were 27.0%, 15.1%, 10.3%, and 7.8%. Table 1 presents the 4-year OS and rwPFS rates stratified by histological type, tumor programmed death ligand 1 (PD-L1) expression level, and Eastern Cooperative Oncology Group (ECOG) performance status. Patients with lower PD-L1 expression level (&amp;lt;1%), worse ECOG performance status (≥2), and squamous cell carcinoma had worse survival outcomes, regardless of the type of 1L treatment received. Conclusions: The real-world survival rates for patients with aNSCLC who were treated with 1L IO-based regimens were lower than those observed in pivotal trials, which indicates an unmet need for the management of newly-diagnosed aNSCLC. However, on average approximately 1 in 11 pts receiving IO monotherapy and 1 in 13 pts receiving IO + chemotherapy remained progression-free at the four year landmark and achieved an extended period of survival. Table: 4-year OS and rwPFS rates 1L IO monotherapy 1L IO + chemotherapy PD-L1 &amp;lt;1% PD-L1 ≥1-49% PD-L1 ≥50% PD-L1 &amp;lt;1% PD-L1 ≥1-49% PD-L1 ≥50% OS by histological type (sample size; 4-year rate, %) Squamous 122; 12.7 329; 14.0 814; 15.1 585; 11.7 647; 15.1 295; 23.3 Non-squamous 231; 16.7 516; 20.0 2563; 26.3 2263; 14.9 2058; 20.8 1313; 28.9 OS by ECOG performance status (sample size; 4-year rate, %) 0-1 193; 17.0 439; 20.8 1880; 27.6 1852; 16.8 1802; 21.9 1065; 28.0 ≥2 89; 6.7 261; 14.5 840; 12.7 478; 5.6 452; 11.1 241; 22.8 rwPFS by histological type (sample size; 4-year rate, %) Squamous 122; 7.6 329; 4.4 814; 6.8 585; 5.2 647; 8.3 295; 9.2 Non-squamous 231; 5.1 516; 10.0 2563; 11.2 2263; 4.3 2058; 6.3 1313; 14.7 rwPFS by ECOG performance status (sample size; 4-year rate, %) 0-1 193; 6.9 439; 10.4 1880; 11.9 1852; 5.4 1802; 6.8 1065; 14.5 ≥2 89; NA 261; 3.7 840; 5.0 478; 2.2 452; 3.9 241; 8.2 Citation Format: David Waterhouse, Saurabh Ray, Keith A. Betts, Sophie Gao, Yong Yuan, Manasvi Sundar, Shumin Rui, David Stenehjem. Real-world long-term survival outcomes of first-line immunotherapy-based regimens in advanced non-small cell lung cancer [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 3819.

Real-World Immunotherapy Use and Effectiveness in Advanced NSCLC With Programmed Death-Ligand 1 Greater Than or Equal to 50% and Greater Than or Equal to 90%

4558 Background: The NIVES study represents the first prospective trial with NIVO in combination with SBRT in pre-treated mRCC patients. This study did not meet the primary endpoint in terms of objective response rate (ORR) as previously reported. However this combination showed a faster time to treatment response, a long progression free survival and median duration of response without increasing toxicities. Here we have tested with an exploratory analysis the correlation between PD-L1 expression and clinical outcomes in pts treated with NIVO plus SBRT. Methods: PD-L1 expression was assessed in archival collected tumour samples in our central laboratory using 4 commercial kits for immunoistochemical (ICH) analysis (clone 22C3 pharm DX Dako Agilent, 28.8 Abcam and SP142 and SP263 Ventana Medical System). A tumor cell was considered positive if any membranous staining was found regardless of the intensity. In particular the immunostaining was scored 0 when all tumor cells were unstained (PD-L1-negative), 1+ when &lt; 1% positive tumor cells were counted, 2+ when the percentage was between 1% and 50%,3+ when the number of stained cells was more than 50%. ORR and overall survival (OS) were correlated with PD-L1 staining. Results: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 44 of 69 pts enrolled in the NIVES study. Twenty-two pts of 44 (50%) were considered PD-L1-negative using all the 4 commercial kits for ICH analysis, while 14 of 44 pts (31,8%) were defined PD-L1 weakly positive (positive tumor cells &lt; 1% at least in one kit for ICH). Eight of 44 pts (18.1%) were defined PD-L1 strong positive when at least one kit for ICH scored 2+ or 3+. About the correlation between ORR and PDL1 staining in the 42 pts (2/44 pts are not evaluable for ORR), ORR was 18.2% (95% CI, 5.2% to 40.3%) in the PD-L1-negative group vs 20% (95% CI, 5.7% to 43.7%) in weakly/strongly PD-L1 positive (p = 1.00). Among the 44 pts in the intention-to-treat population with available PD-L1 status, median OS was not significantly different between pts with PD-L1 negative (20.56 months, 95% CI, 7.16 to NR) and PD-L1 positive (18.33 months, 95% CI, 6.83 to NR) (p = 0.56). Conclusions: For the first time four commercial kits for ICH analysis were used to test PD-L1 expression in pretreated mRCC pts. Data from these small sample size seem to confirm that PD-L1 in pre-treated mRCC cancer is not a predictive biomarker for selecting pts to receive NIVO-based treatment. Clinical trial information: NCT03469713.

MA07.11 Survival Outcomes Based on Gender of Advanced Nonsmall Cell Lung Cancer Patients Treated with Pembrolizumab or Nivolumab in Everyday Clinical Practice