SP142 Assay Research Articles

Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma

Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.

A preliminary study on the diagnostic performance of the uPath PD-L1 (SP263) artificial intelligence (AI) algorithm in patients with NSCLC treated with PD-1/PD-L1 checkpoint blockade.

The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay. In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice. 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS. This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC.

PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.

The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.

Atezolizumab versus placebo in combination with bevacizumab and non-platinum-based chemotherapy in recurrent ovarian cancer: Final overall and progression-free survival results from the AGO-OVAR 2.29/ENGOT-ov34 study.

LBA5501 Background: Paclitaxel or pegylated liposomal doxorubicin (PLD) in combination with bevacizumab (bev) are standard treatment options in patients with relapsed ovarian cancer not candidates for platinum, but responses are usually short-lived. Recently, two trials have reported a numerical but non-significant advantage from the addition of atezolizumab (atezo) to chemo plus bev in the recurrent setting (ATALANTE, Kurtz JE et al., J Clin Oncol &amp; NRG GY009, O'Cearbhaill et al, IGCS 2023). AGO-OVAR 2.29 investigated the efficacy of atezo in combination with bev and non-platinum-based chemo. Methods: AGO-OVAR 2.29 is a randomized, double blind, phase III trial evaluating the efficacy and safety of atezo plus bev and chemo in patients (pts) with recurrent ovarian cancer. Eligible patients had a 1st/2nd relapse within 6 months after completing platinum-based chemo or a 3rd relapse regardless of treatment-free interval. A fresh biopsy for central PD-L1 testing (VENTANA SP142 assay) prior to randomization was mandatory. All pts received weekly paclitaxel or PLD and bev until disease progression or intolerable toxicity and were randomized 1:1 to either atezolizumab 840 mg q14 days or placebo until progression or for a maximum duration of 24 months. Number of prior lines, planned chemo, prior bev and PD-L1 status served as stratification factors. Overall survival (OS) and progression-free survival (PFS) in the intention to treat (ITT) population were primary endpoints, both to be analyzed after observation of 391 deaths. Data cut-off (DCO) occurred on 26/01/2024. OS and PFS analysis is based on a multiple Cox regression with treatment arm and stratification factors as covariates. Safety is reported for pts who received at least one dose of study treatment. Results: 574 pts were randomly assigned to atezo (285) or placebo (289). 45.1% received PLD and 53.7% paclitaxel. 7 pts did not start study treatment. 36.1% of pts had received 3 prior lines and 72.5% prior bev. 25.8% were PD-L1 positive. At DCO 418 OS and 505 PFS events have occurred. Median OS was 14.3 months (mos) in the atezo and 13.0 mos in the placebo arm (HR 0.83, 95% CI 0.68-1.01; p=0.06) and PFS 6.3 mos for atezo vs 6.6 mos for placebo arm (HR 0.88, 95% CI 0.73-1.05; p=0.15). Similar HR were observed in PD-L1 positive and negative pts. In total, 580 SAE and 141 AESI were reported. AEs of ≥ grade 3 were reported in 71.5% in the atezo and 68.9% in the placebo arm. 63.7% of pts in the atezo and 51.4% in the placebo arm experienced serious AEs. Conclusions: The addition of atezo to chemo plus bev did not significantly improve OS or PFS in pts. with recurrent ovarian cancer who are no candidates for platinum. Safety was within the expected range. Translational research is ongoing. Clinical trial information: NCT03353831 .

Digital versus manual pathology scoring of PD-L1 in patients with esophageal squamous cell carcinoma (ESCC).

e16023 Background: Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with ESCC, but the association between PD-L1 and clinical outcomes of patients with ESCC receiving ICIs treatment is unclear. Currently, different PD-L1 antibody clones, scoring, and cutoffs were used for different ICIs development in ESCC. Thus, we develop a digital pathology (DP) algorithm to generate multiple scores at the same time with high reproducibility. We evaluate DP algorithm by: (1) comparing the digital and manual scores of SP263 and 22C3 assays; (2) evaluating the association with OS. Methods: Tumor tissue samples were collected from ESCC patients treated at National Taiwan University Hospital between 2017 and 2020. Slides were tested for PD-L1 using SP263 and 22C3 assays at a College of American Pathologists accredited central laboratory. H&amp;E and PD-L1 slides were scanned for whole slide images (WSIs) using DP200 scanner at 20x. HALO (v3.5) by indica labs was used for DP development by deep learning neural network algorithms. WSIs of SP263 were annotated for region of interest (ROI), tumor/stroma area, and tumor, immune and fibroblast cells by board certified pathologists. After the algorithm is developed and run on SP263 WSIs, a board-certified pathologist reviewed the images and provided an agreement score of DP markups. The images were excluded if an agreement was less than 80%. This algorithm was then applied to 22C3 WSIs. Data of areas and cells were exported for subsequent statistical analysis using R. We calculated the DP scores based on the definition of manual readouts of TAP, CPS and s/iTILs in ROI and tumor and stroma regions in both clones’ WSIs. These DP scores were compared with manual scores using Spearman’s rank-order correlation. Association with OS were evaluated using cox proportional hazard regression. Results: Of 235 evaluable images, twelve (5.1%) were excluded due to the low agreement with the pathologist's judgment. DP generated scores showed a strong correlation with pathologists scoring (rho = 0.80 for SP263 and rho = 0.74 for 22C3). DP generated CPS-like and TAP-like scores in ROI, and tumor and stroma regions from SP263 and 22C3 also demonstrated a strong correlation between each other (rho: 0.77 - 0.86). However, s/iTILs correlation between DP and pathologist score is negligible (rho: 0.002 - 0.34). While examining the association of PD-L1 scores and s/iTILs with OS, no clear associations were found with either DP or pathologists’ scores, after adjusting for stage, ECOG, age and gender. Conclusions: DP algorithms developed in this study demonstrated the efficiency of generating multiple DP scores of CPS, TAP, and s/iTILs from one image at the same time, which performed comparable to manual scores. DP algorithm developed based on SP263 is generalizable to 22C3 and showed a good performance. Further algorithm adjustment will be made to overcome the misclassification in the 12 failed cases.

Avelumab + axitinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial.

4508 Background: The JAVELIN Renal 101 (NCT02684006) phase 3 trial compared first-line treatment with avelumab + axitinib vs sunitinib in aRCC. The trial previously met one of its primary objectives by showing significantly longer progression-free survival (PFS) with avelumab + axitinib vs sunitinib in pts with PD-L1+ tumors; longer PFS, higher objective response rate (ORR), and an acceptable safety profile were also observed in the overall population. OS data were immature. Here we report the final analysis. Methods: Pts with untreated aRCC (any IMDC risk score) were randomized 1:1 to avelumab + axitinib or sunitinib. OS and PFS (by blinded independent central review) in pts with PD-L1+ tumors (SP263 assay) were independent primary endpoints. OS and PFS in the overall population were key secondary endpoints; response and safety were also analyzed. Results: Of 886 pts randomized, 560 (63.2%) had PD-L1+ tumors. At data cutoff (August 31, 2023), median follow-up in the avelumab + axitinib and sunitinib arms was 73.7 and 73.6 months, respectively (≥68 months in all pts). Final efficacy data are shown in the Table. In the avelumab + axitinib and sunitinib arms, grade ≥3 TRAEs occurred in 66.8% vs 61.5%, respectively. Second-line therapy was received by 58.1% vs 69.4%, including a PD-(L)1 inhibitor in 18.8% vs 53.6%, respectively. Conclusions: The JAVELIN Renal 101 trial provides the longest follow-up for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial reported to date. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance. PFS was longer with avelumab + axitinib vs sunitinib, and responses were durable in a subset of pts. Final analysis results confirm the long-term efficacy and manageable safety profile of avelumab + axitinib treatment in pts with aRCC. Clinical trial information: NCT02684006 . [Table: see text]

PD-L1 immunohistochemistry in gastric cancer: Comparison of combined positive score and tumor area positivity across 28-8, 22C3, and SP263 assays.

2625 Background: The clinical application of programmed death-ligand 1 (PD-L1) immunohistochemistry is complicated by multiple available assays and different testing platforms, scoring algorithms, and cut-offs applied. This study assessed the analytical comparability of three commercially available PD-L1 assays (28-8, 22C3, and SP263) and two scoring algorithms used in gastric cancer (GC). Methods: Serial sections of 100 commercially procured GC samples, selected by the 28-8 assay to represent the dynamic range of PD-L1 expression, were stained with the three in vitrodiagnostic (IVD)-grade PD-L1 assays. Stained slides were blindly and independently evaluated by three trained pathologists for intra- and inter-reader assessment. Scoring was performed using the combined positive score (CPS) and tumor area positivity (TAP) methods, followed by statistical analysis. Digital image analysis (DIA) was used to objectively assess the technical performance of each assay by simulating CPS and TAP scoring methods using the HALO platform. Results: Comparable, specific, staining patterns were observed with the three PD-L1 assays. Pathologist assessment of PD-L1 positivity was reproducible in GC sample cohorts despite discernible variability in the observed staining intensity. When the same PD-L1 cut-offs were applied, inter- and intra-assay assessments of all three assays, using either CPS or TAP scoring methods, demonstrated moderate to almost-perfect (inter-assay Cohen’s kappa [κ] ranged from 0.47 to 0.83) and substantial to almost-perfect (intra-assay κ ranged from 0.77 to 1.00) agreement, respectively. Moreover, inter-pathologist evaluation showed a significant level of reproducibility (intraclass correlation coefficient (ICC) ≥0.92). DIA confirmed no difference in technical performance when specific digital algorithms were applied. Conclusions: This GC study highlights analytical concordance in PD-L1 testing among three major PD-L1 assays when TAP and CPS scoring algorithms are prospectively applied. Independently, DIA further supports the comparability of the technical performance of the assays. These observations support flexibility in cross-application of the different PD-L1 assays and scoring algorithms currently used to characterize PD-L1–positive GC samples.

Comparison of SP263 and 22C3 pharmDx assays to test programmed death ligand-1 (PD-L1) expression in surgically resected non-small cell lung cancer.

Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II-IIIA non-small cell lung cancer with 1% or more programmed death ligand-1 (PD-L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non-small cell lung cancer. Therefore, our study aimed to compare two PD-L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab. We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD-L1 expression between SP263 and 22C3 assays. The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522-0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639-0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD-L1 expression with 22C3 resulted slightly higher than that with SP263. This study showed a high concordance of PD-L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required.

Abstract LBO1-03: Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N)

Abstract Background: A previous clinical study suggested that a priming dose of programmed cell death ligand 1 (PD-L1) inhibitor monotherapy 2 weeks prior to addition of chemotherapy could be more efficacious than starting all agents concurrently. Furthermore, the addition of checkpoint therapy may allow shorter chemotherapy duration in selected patients. The aim of this study was to investigate the strategies of lead-in Nivolumab (N) monotherapy and starting concurrent N with 12 weeks of carboplatin and paclitaxel in TNBC. Methods: In this multicenter Phase II study, eligible patients with stage I (cT1c)-II TNBC were randomized to receive either Arm A (lead-in): N 240 mg monotherapy, followed 2 weeks later by N 360mg + carboplatin (AUC 5) every 21 days x 4 cycles + weekly paclitaxel (80 mg/m2) for 12 weeks; or Arm B (concurrent): same agents initiated concurrently given over 12 weeks, followed 2 weeks later by N 240mg monotherapy, prior to surgery. The primary endpoint was pathological complete response (pCR ypT0/Tis ypN0). Secondary endpoints are residual cancer burden (RCB), safety, response according to baseline stromal tumor infiltrating lymphocytes (sTILs) quantity and PD-L1 expression and event-free survival (EFS). sTIL high was defined as ≥30% and PD-L1 positive as ≥1% (SP142 assay). A non-comparative Simon two-stage design was used to test the null hypothesis, in each Arm separately, of a pCR rate ≤40% vs an alternative pCR rate of ≥60% with 90% Confidence Intervals (CI). No adjuvant N was given, and adjuvant chemotherapy was at the discretion of the investigator in case of non-pCR. Results: 110 patients were randomized from July 2020 to April 2022; 108 patients who initiated treatment were analyzed. Baseline characteristics: median age was 49yrs (IQR 43-60yrs), 16.7% had node-positive disease, 34.3/64.8% had stage I/II disease, 33.3% were sTIL high and 47.2% were PD-L1 positive. For Arms A and B respectively, pCR rates were 50.9% (90% CI:39.0-63.2) and 54.5% (90% CI:42.7-66.2) with an overall pCR rate of 52.8% (90% CI:44.4-61.0). The RCB 0+1 rates were overall 68.5% (90% CI: 60.4-75.9); with 64.2% (90% CI: 52.0-75.1) and 72.7% (90% CI: 61.2-82.4) for Arms A and B respectively. Overall, in the sTIL high vs low subgroups, pCR was 66.7% (CI: 51.7-79.5) vs 45.7% (CI: 35.5-56.2%), and in the PD-L1 positive vs negative subgroups, pCR was 70.6% (CI: 58.4-80.9) vs 33.3% (CI: 21.8-46.6) respectively. pCR was 48.6% in stage I and 54.9% in stage II. Treatment-related adverse events were similar in both arms, with grade 3-4 adverse events in 64.8% patients. Early discontinuation of N occurred in 17 patients (15.7%). Immune related endocrine dysfunction (any grade) was observed in 22 patients (20.4%). Conclusion: The pCR rates exceeding 50% support that 12 weeks of a neoadjuvant non-anthracycline chemotherapy regimen with nivolumab is efficacious for Stage I/II TNBC with either concurrent or lead-in N. This study did not support the hypothesis that lead-in N was associated with a pCR advantage. The regimen was well tolerated, with no new safety signals. Patients with immune enriched tumors, identified by high sTILs or PD-L1 positivity, had very high pCR rates, identifying a subpopulation for whom a 12 week anthracycline-free chemotherapy regimen with N may be appropriate. EFS results are still maturing. Citation Format: Sherene Loi, Samuel Niman, Nicholas Zdenkowski, Prudence Francis, Sally Baron Hay, William Fox, Kevin Punie, Alexander M Menzies, Rebecca Angus, Carlie Mavin, Lauren Rennie, Isobel Stoodley, Bruce Mann, Marion JJ Kuper-Hommel, Meredith Regan. Randomized Phase II Study of Neoadjuvant Nivolumab (N) 2 week lead-in followed by 12 weeks of concurrent N+carboplatin plus paclitaxel (CbP) vs concurrent N+CbP in Triple Negative Breast Cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr LBO1-03.

Abstract PS16-02: Efficacy and safety of first-line atezolizumab + bevacizumab + paclitaxel in patients with advanced triple-negative breast cancer: the ATRACTIB phase 2 trial

Abstract BACKGROUND Triple-negative breast cancer (TNBC) is an aggressive tumor characterized by poor outcomes and new treatment strategies are urgently required. The programmed cell death-ligand 1 (PD-L1) antibody (Ab) atezolizumab (ATZ) combined with first-line (1L) nab-paclitaxel (nab-PTX) is approved in multiple countries for the treatment of PD-L1-positive patients (pts) with advanced TNBC (aTNBC) based on a significant improvement in progression-free survival (PFS) and a numerically higher and clinically meaningful median overall survival (OS). A synergism between antiangiogenic therapy and immunotherapy (IO)-based strategies has been observed preclinically and in different tumor types, but data in aTNBC is lacking. METHODS ATRACTIB (NCT04408118) is an international, open-label, single-arm, phase 2 trial evaluating the efficacy and safety of 1L ATZ + BVZ + PTX for pts with aTNBC, regardless of their tumors’ PD-L1 status. Adult pts with untreated, unresectable locally advanced/metastatic TNBC were included. Pts who had received (neo)adjuvant taxane-based chemotherapy (CT) and/or IO and/or an antiangiogenic agent had to have had a relapse with a disease-free interval beyond 12 months (mo). Pts received intravenous ATZ 840 mg + BVZ 10 mg/kg on days (D)1 and D15 + PTX 90 mg/m2 on D1, 8, and 15 of every 28-day cycle until disease progression, intolerable toxicity, death, or patient withdrawal. Tumor assessments were performed every 8 weeks for the first 12 mo and every 12 weeks thereafter. Baseline PD-L1 expression was centrally assessed using 22C3 (combined positive score [CPS]) and SP142 (expression on tumor-infiltrating immune cells [ICs]) Abs. The primary endpoint was investigator-assessed PFS by RECIST v.1.1. Key secondary endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), and safety. Median PFS was analyzed with exponential maximum likelihood estimation (H0: ≤7.0 mo; HA: ≥9.5 mo). We estimated that enrolling 100 pts would provide 80% power at one-sided α nominal level of 5%, assuming a 10% drop-out rate. RESULTS Between October 2020 and May 2022, 100 female pts from 28 centers across 5 European countries were included. Median age was 55.0 years (32.0 - 84.0), 57.0% of pts had visceral disease, 46.0% had ≥3 metastatic sites, and 70.0% had received prior treatment for early BC (taxane-based CT in 87.1% of them). A total of 82 and 85 tumor samples out of 100 pts were available for PD-L1 assessment using 22C3 and SP142 assays, respectively. Most pts had PD-L1-negative tumors (87.8% with 22C3 [CPS &amp;lt; 10] and 97.6% with SP142 [expression on &amp;lt; 1% positive of ICs]). At data cutoff (15th September 2023), 23 pts were still on therapy. With a median follow-up of 16.7 mo (1.1 - 34.1), median PFS was 11.0 mo (95% CI, 9.0 - 13.2). OS data were immature at data cutoff, with 30 events. Estimated 18-month OS was 69.4% (95% CI, 58.4% - 78.1%). ORR was 63.0% (95% CI, 52.8% - 72.4%), CBR was 79.0% (95% CI, 69.7% - 86.5%), and median DoR was 10.0 mo (95% CI, 7.2 - 13.8). Regarding safety, the most common treatment-emergent adverse events (TEAEs) were peripheral neuropathy (68.0%) and fatigue (62.0%). Grade (G) 3/4 treatment-related TEAEs occurred in 47.0% of pts, mainly peripheral neuropathy (13.0%) and neutropenia (12.0%). Any-grade immune-related TEAEs, thrombosis or embolism, and bleeding occurred in 13.0% (5.0%; G≥3), 4.0% (1.0%; G≥3), and 10.0% (0.0%; G≥3) of pts, respectively. There were no drug-related deaths. CONCLUSIONS 1L ATZ + BVZ + PTX demonstrated encouraging anti-tumor activity in aTNBC pts, most of them presenting with PD-L1-negative tumors. Median PFS seems to be much higher compared with that previously reported with other IO-based regimens in a similar patient population. The safety profile was consistent with the known safety data of ATZ and BVZ combined with CT, without significant added toxicity. These results merit further research of this combination for PD-L1-negative aTNBC. Citation Format: Maria Gion, Patricia Cortez-Castedo, Isabel Blancas, Alfonso Cortés, Frederik Marmé, Salvador Blanch, Serafin Morales Murillo, Nieves Díaz, Isabel Calvo-Plaza, Sabela Recalde, Alejandro Martínez-Bueno, Manuel Ruiz-Borrego, Elisenda Llabres, María Teresa Taberner, Michelino de Laurentiis, José Ángel García-Sáenz, Jana Repkova, Antonio Antón, Joseph Gligorov, Susana de la Cruz, Oliver Hoffmann, Jacques Medioni, Melissa Phillips, Miguel Sampayo-Cordero, Daniel Alcalá-López, José Manuel Pérez-García, Antonio Llombart-Cussac, Javier Cortés. Efficacy and safety of first-line atezolizumab + bevacizumab + paclitaxel in patients with advanced triple-negative breast cancer: the ATRACTIB phase 2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-02.

Abstract GS01-01: Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: an Exploratory Analysis of CheckMate 7FL

Abstract Background: CheckMate 7FL (CM 7FL; NCT04109066) is a prospective, phase 3, randomized, multicenter, double-blind trial investigating nivolumab (NIVO) in combination with neoadjuvant chemotherapy (NACT) and adjuvant endocrine therapy (ET) in patients (pts) with high-risk, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC). The primary endpoint (pathological complete response, pCR) was met, resulting in a statistically significant improvement with added NIVO to NACT; residual cancer burden (RCB) 0–1 rate was meaningfully improved. NIVO benefit was larger in pts with PD-L1+ tumors (SP142 assay, % immune cells ≥ 1%). This analysis focuses on additional biomarkers to explore associations with NIVO treatment effect. Methods: The study enrolled newly diagnosed pts, stages T1c–2 N1–2 or T3–4 N0–2, grade 2 (ER 1–‍10%) or 3 (ER ≥ 1%). Pts were randomized 1:1 to NACT + NIVO 360 mg Q3W/NIVO 240 mg Q2W (arm A) or NACT + placebo (PBO; arm B). Clinical efficacy data included pCR (ypT0/is ypN0) and RCB 0–1 rates in the modified ITT (mITT) population and the SP142 PD-L1+ subgroup. Baseline PD-L1 expression from core biopsies was evaluated with the Dako 28-8 assay using the combined positive score (CPS) algorithm. Various cutoffs (CPS ≥ 1, 10, and 20) were used for this exploration. Concordance between PD-L1 SP142 and 28-8 CPS was evaluated, with assays performed on different slides from the same tumor biopsy blocks. Results of efficacy by ER and/or progesterone receptor (PR) expression, as well as Ki67 index and stromal tumor-infiltrating lymphocytes, will be presented at the meeting. Results: Overall, 830 pts were screened, 521 randomized, and 517 treated, with the primary efficacy population (mITT; n = 510) including all randomized pts but excluding 11 pts from Russian sites with insufficient follow-up. A total of 510 and 349 pts (68.4% of mITT population) were evaluated by PD-L1 SP142 and 28-8 CPS assays, respectively. The prevalence of PD-L1+ by CPS was balanced in arms A and B (52% vs 50% had CPS ≥ 1; 19% vs 16% had CPS ≥ 10, and 11% vs 9% had CPS ≥ 20, respectively). NIVO effect was larger in pts with tumors with increasing PD-L1 expression, with a ∆pCR rate (unweighted rate difference between arms A and B) of 16.6% in CPS ≥ 1 (40.4% vs 23.8% in arms A/B; 95% CI, 2.8 to 29.4), 32.4% in CPS ≥ 10 (65.7% vs 33.3% in arms A/B; 95% CI, 7.3 to 52.3), and 52.3% in CPS ≥ 20 (78.9% vs 26.7% in arms A/B; 95% CI, 18.6 to 72.4). In comparison, the ∆pCR rate was 10.7% in the mITT population (24.5% vs 13.8% in arms A/B; 95% CI, 3.9 to 17.4) and 5.7% in pts with CPS &amp;lt; 1 (14.0% vs 8.2% in arms A/B; 95% CI, -4.0 to 15.5; refer to the Table for additional details). Unweighted rate differences between arms A and B for RCB 0–1 (∆RCB 0–1 rate) followed a similar trend and were observed to be 17.0% in CPS ≥ 1, 34.4% in CPS ≥ 10, and 52.3% in CPS ≥ 20. In comparison, the ∆RCB 0–1 rate was 9.4% in the mITT population and 3.3% in pts with CPS &amp;lt; 1 (refer to the Table for additional details). Further biomarker data and cutoffs will be presented at the meeting. Conclusions: Greater PD-L1 expression was associated with higher pCR and RCB 0–1 rates, suggesting that pts with PD-L1+, high-risk, ER+/HER2− primary BC can achieve substantial pCR rates with the addition of NIVO to NACT. Table. Summary pCR and RCB 0–1 rates by PD-L1 SP142 and 28-8 CPS at various cutoffs. Note: CPS data with the cutoff at 5 will be presented at the meeting. Citation Format: Sherene Loi, Giuseppe Curigliano, Roberto Salgado, Roberto Iván Romero Díaz, Suzette Delaloge, Carlos Ignacio Rojas García, Marleen Kok, Cristina Saura, Nadia Harbeck, Elizabeth Mittendorf, Denise Yardley, Lajos Pusztai, Alberto Suárez Zaizar, Andrei Ungureanu, Felipe Ades, Rajalakshmi Chandra, Raheel Nathani, Misena Pacius, Thomas Spires, Jenny Wu, Heather McArthur. Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: an Exploratory Analysis of CheckMate 7FL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-01.

Clinical significance of inter-assay discrepancy in PD-L1 evaluation for the efficacy of pembrolizumab in advanced NSCLC with high PD-L1 expression

IntroductionProgrammed cell death ligand-1 (PD-L1) expression is a predictive biomarker for the efficacy of anti-programmed cell death receptor-1/PD-L1 antibodies in advanced non-small cell lung cancer (NSCLC). Although several assays have been approved for evaluating PD-L1 expression status, inter-assay discordance has been observed between some assays. The clinical significance of these discrepancies is still unclear. MethodsWe retrospectively reviewed treatment-naïve NSCLC patients whose PD-L1 expression was evaluated using both 22C3 and SP142 assays. Among those, efficacy analysis was performed for patients with PD-L1 tumor proportion score (TPS) ≥ 50 % (22C3), who had received first-line pembrolizumab monotherapy. Additionally, transcriptome analysis was conducted in the available tumors with TPS ≥ 50 % to investigate the distinct immune profiles that accompany inter-assay discordance. ResultsIn total, 611 patients were eligible. Among 198 patients with TPS ≥ 50 %, 91 (46 %) had tumor cell score ≤ 1 (SP142, i.e., inter-assay discrepancy). In the 52 patients who received first-line pembrolizumab monotherapy, treatment efficacy was significantly lower in patients with the discrepancy than that in those without (objective response rate: 18 % vs. 83 %, p < 0.001; median progression-free survival [months]: 3.2 vs. 8.3, p < 0.001). Transcriptome analysis revealed significantly more CD274 splice variants with aberrant 3′-terminal sequences in tumors with the inter-assay discrepancy than in those without. ConclusionThe inter-assay discrepancy in the PD-L1 status of tumor cells between the 22C3 and SP142 assays, reflecting an imbalance in the CD274 splice variants, could be a biomarker for primary resistance against pembrolizumab monotherapy in high PD-L1-expressing NSCLCs.

Abstract 5146: Clinical significance of inter-assay discrepancy in PD-L1 expression evaluation for the efficacy of pembrolizumab in advanced NSCLC patients with high PD-L1 expression

Abstract Introduction: The expression of programmed cell death ligand-1 (PD-L1) is a predictive biomarker for the efficacy of pembrolizumab in advanced non-small cell lung cancer (NSCLC). While several assays have been approved for evaluating PD-L1 expression status, the inter-assay discordances are observed. The clinical significance of these discrepancies is still unclear. Methods: We retrospectively reviewed treatment-naïve NSCLC patients with available PD-L1 expression status by both 22C3 and SP142 assays. Among these patients, efficacy analysis was performed in those with PD-L1 tumor proportion score (TPS) ≥ 50% (22C3) who received the first-line pembrolizumab monotherapy. Additionally, we conducted RNA-sequence analysis in the patients with TPS ≥ 50% to investigate the distinct immune profiles with the inter-assay discordance. Results: A total of 611 patients were evaluated for PD-L1 expression status by both assays. Of 198 patients with TPS ≥ 50%, 91 (46%) had TC score ≤ 1 (SP142, i.e., inter-assay discrepancy). In 52 patients who received the first-line pembrolizumab monotherapy, the efficacy in patients with the inter-assay discrepancy was significantly lower than those without the discrepancy (shown in Table). While there was no difference in tumor microenvironments such as the tumor-infiltrating lymphocytes, the transcriptome analysis revealed significantly more CD274 splicing variants with aberrant 3’-terminal sequences in tumors with the inter-assay discrepancy than those without discrepancy, leading to the suppressed PD-1/PD-L1 pathway in those with the discrepancy. Conclusion: The inter-assay discrepancy in the PD-L1 expression status on tumor cells between the 22C3 and SP142 assays, reflecting an imbalance of the CD274 splicing variants, could be a primary-resistance mechanism to the pembrolizumab monotherapy in highly PD-L1-expressing NSCLCs. PD-L1(22C3) Discrepancy Pts. ORR(%) p value Median PFS(months) 95%CI p value TPS ≥ 50% yes 17 18 &amp;lt; 0.001 3.2 0.8–5.5 &amp;lt; 0.001 no 35 83 8.3 5.7–24.2 Citation Format: Jun Miyakoshi, Jumpei Kashima, Masayuki Shirasawa, Masahiro Torasawa, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Tatsuya Yoshida, Yasushi Goto, Hidehito Horinouchi, Kouya Shiraishi, Takashi Kohno, Noboru Yamamoto, Yasushi Yatabe, Yuichiro Ohe. Clinical significance of inter-assay discrepancy in PD-L1 expression evaluation for the efficacy of pembrolizumab in advanced NSCLC patients with high PD-L1 expression [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 5146.

Abstract 2492: Enhanced patient selection for anti-PD-L1 treatment in metastatic NSCLC with quantitative continuous scoring of PD-L1

Abstract Background: Anti-PD-L1 therapy has demonstrated clinical activity in patients with metastatic non-small cell lung cancer (mNSCLC). However, only subgroups of patients respond and their identification via PD-L1 as a biomarker remains imperfect. PD-L1 expression is commonly assessed by pathologist tumor cell (TC) scoring of immunohistochemically (IHC) stained tissue. We developed a system for digitally scoring PD-L1 in IHC (PD-L1 QCS), which demonstrated robust scoring across studies [1]. Here, we present a comparison of PD-L1 QCS against manual scoring of PD-L1 (SP263 assay, Ventana) in the MYSTIC clinical trial. Methods: PD-L1 QCS on digitized whole slide images (WSI) comprises two deep learning models, enabling segmentation of single TCs followed by PD-L1 expression quantification via their optical density (OD). Positive cells are classified based on an OD threshold, allowing robust digital calculation of the TC percentage [1]. The analysis included 502 WSI from the MYSTIC trial (NCT02453282), representing 256 patients treated with anti-PD-L1 therapy and 246 treated with chemotherapy as standard-of-care (SoC) [2]. First, an optimal cut-point was determined by optimization against outcome, classifying patients with ≥0.575% TC as biomarker positive (BM+). Next, the approach was compared against manual TC scoring at 1%, 25% and 50% cut-off. Results: In durvalumab treated patients, median overall survival (mOS) in the PD-L1 QCS BM+ subgroup (prevalence 54.3%) was 12.1 months longer than in the BM- subgroup (19.9m vs. 7.8m, HR=0.45, CI [0.33, 0.60]). Analogous comparison of subgroups based on manually scored TC proportion at 1% (prev. 75.0%), 25% (prev. 42.6%) or 50% (prev. 29.7%) cut-points yielded a mOS difference of 7.8m (HR=0.52, CI [0.38, 0.72]), 8.3m (HR=0.61, CI [0.45, 0.82]) and 11.0m (HR=0.55, CI [0.40, 0.77]) respectively. Comparing durvalumab treatment against SoC within the PD-L1 QCS BM+ subgroup yielded a HR of 0.62 (CI [0.46, 0.82], log rank p=0.0008, 7.4m mOS delta). In comparison, a HR of 0.69 (CI [0.46,1.02], p=0.0642, 8.4m mOS delta) was obtained for manual TC scoring at 50%. Conclusion: We compared a computational pathology approach for continuous PD-L1 scoring for the selection of mNSCLC patients for anti-PD-L1 treatment against established manual scoring. Our results suggest that PD-L1 QCS has the potential to identify a larger patient subgroup that retains benefit from anti-PD-L1 treatment and more precisely identifies non-responders.

Abstract 7617: Quantitative continuous scoring of PD-L1 for superior patient selection for anti-PD-L1 treatment of locally advanced or unresectable NSCLC

Abstract Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 following concurrent chemoradiotherapy (cCRT) have shown clinical activity in locally advanced, unresectable NSCLC, e.g. with the PACIFIC regimen [1]. PD-L1 expression is typically assessed by pathologist scoring of immunohistochemically (IHC) stained tissue using the tumor cell (TC) score. In this work, we present PD-L1 Quantitative Continuous Scoring (PD-L1 QCS) to digitally assess PD-L1 expression (Ventana SP263 assay), and analyze its utility for identification of patient subgroups with higher likelihood of treatment response. Method: 368 digitized whole slide images (WSI) of fresh biopsy and archival samples were obtained from the PACIFIC trial (NCT02125461), including 126 patients who received placebo and 242 patients who received Durvalumab post-cCRT [1]. WSI analysis included two deep learning models for epithelial TC segmentation followed by optical density (OD) quantification of membrane expression [2]. Initially, PD-L1 QCS was calibrated to compute the TC score at 1% cutoff by determining an optimal OD cell positivity threshold. Next, other scoring approaches were investigated, which included various OD thresholds and biomarker cutoffs. Results: PD-L1 QCS-based TC scoring was able to maintain median overall survival (mOS) of 57.4 months in the biomarker positive (BM+) ICI cohort, while increasing prevalence to 191 out of 242 patients (78.9%) compared to 177 (73.1%) with manual TC score at 1% cutoff. Extending the scoring paradigm to the PD-L1+ TC density &amp;gt;= 542.5 cells/mm² lead to a more pronounced increase of prevalence to 200 patients (82.6%) in the ICI population, while mOS was not reached and additionally showed comparable hazard ratios (HR) when evaluating against the BM+ placebo cohort (HR=0.54 [0.39, 0.76] resp. HR=0.52 [0.37, 0.74]). Results further demonstrated that PD-L1 QCS density scoring of the ICI treated population allowed for a clearer separation of patients with less treatment benefit (34.2m mOS, N=42, log rank p=0.0067) compared to manual scoring (47.4m mOS, N=65, log rank p=0.2). Conclusion: We investigated a computational pathology approach for selecting patients for treatment with the PACIFIC regimen and compared it against established manual pathology scoring. Results indicate that PD-L1 QCS TC proportion scoring can increase prevalence, while PD-L1 QCS TC density scoring has the potential to identify an even larger patient subgroup with increased survival benefit.

Comparing Three Different Anti–Programmed Death-Ligand 1 Antibodies in Immunohistochemical Evaluation of Combined Chemoimmunotherapy Response in Patients With NSCLC: A Prospective Study

IntroductionMultiple programmed death-ligand 1 (PD-L1) immunohistochemistry assays performed using different antibodies including DAKO 22C3, DAKO 28-8, and Ventana SP142 PD-L1—predictive markers for response to various immune checkpoint inhibitors in NSCLC—have been approved in several countries. The differences in multiple PD-L1 immunohistochemistry assay results in predicting the therapeutic response to combined chemoimmunotherapy in patients with NSCLC remain unclear. MethodsIn this multicenter prospective observational study, we monitored 70 patients with advanced NSCLC treated with combined chemoimmunotherapy at 10 institutions in Japan. The expression of PD-L1 in pretreatment tumors was evaluated using the 22C3, 28-8, and SP142 assays in all patients. ResultsThe PD-L1 level in tumor cells determined using the 22C3 assay was the highest among the three assays performed with different antibodies. According to the 22C3 assay results, the PD-L1 tumor proportion score greater than or equal to 50% group had a significantly longer progression-free survival period than the PD-L1 tumor proportion score less than 50% group. Nevertheless, the other assays did not reveal remarkable differences in the objective response rate or progression-free survival. ConclusionsIn our study, PD-L1 expression determined using the 22C3 assay was more correlated with the therapeutic response of patients with NSCLC treated with combined chemoimmunotherapy than that determined using the 28-8 and SP142 assays. Therefore, the 22C3 assay may be useful for clinical decision-making for patients with NSCLC treated with combined chemoimmunotherapy. Trial registration number: UMIN 000043958.

Concordance of assessments of four PD-L1 immunohistochemical assays in esophageal squamous cell carcinoma (ESCC)

ObjectiveGiven real-world limitations in programmed death-ligand 1 (PD-L1) testing, concordance studies between PD-L1 assays are needed. We undertook comparisons of PD-L1 assays (DAKO22C3, Ventana SP263, Ventana SP142, E1L3N) among observers in esophageal squamous cell carcinoma (ESCC) to provide information on the analytical and clinical comparability of four PD-L1 IHC assays.MethodsParaffin embedded samples of 50 cases of esophageal squamous cell carcinoma were obtained, satined with all four PD-L1 assays. PD-L1 was evaluated by 68 pathologists from 19 different hospitals. PD-L1 expression was assessed for combined positive score (CPS).ResultsThe expression sensitivity of SP263 was the highest in ESCC, followed by 22C3, E1L3N and SP142. Taking CPS 10 as the critical value, inter-observer concordance for CPS scores among 68 physicians was assessed for the 22C3, SP263, SP142, and E1L3N assays, yielding values of 0.777, 0.790, 0.758, and 0.782, respectively. In the comparison between assays, the overall CPS scores concordance rates between 22C3 and SP263, SP142, and E1L3N were 0.896, 0.833, and 0.853, respectively. 22C3 and SP263 have high concordance, with OPA of 0.896, while E1L3N and SP142 have the highest concordance, with OPA of 0.908.ConclusionIn ESCC, the concordance of PD-L1 evaluation among observers is good, and the immune cell score is still an important factor affecting the concordance of interpretation among observers. Cases near the specific threshold are still the difficult problem of interpretation. SP263 had the highest CPS score of the four assays. SP263 cannot identify all 22C3 positive cases, but had good concordance with 22C3.E1L3N and SP142 showed high concordance.

PD-L1 testing in metastatic triple-negative breast cancer: Interobserver and interplatform reproducibility of CE-IVD assays for CPS and IC scores

PD-L1 test is recommended in different types of tumors to select patients eligible for immune checkpoint inhibitors (ICI) therapy. Several factors make this test challenging in metastatic triple-negative breast cancer (mTNBC). Different assays and platforms are available, each associated with distinct scoring systems and threshold values specific to the ICI compound used, i.e. CPS≥10 for pembrolizumab and IC ≥ 1 % for atezolizumab. Our objective was to assess the consistency of PD-L1 testing in mTNBC by examining interobserver and interassay reproducibility.We assessed n = 60 mTNBC samples for PD-L1 testing using 22C3 pharmDx assay on a Dako Autostainer Link 48 and VENTANA PD-L1 (SP263) on a Ventana BenchMark Ultra. Additionally, a subset of n = 19 samples was tested using the SP142 assay, also on the Ventana BenchMark Ultra. CPS with both 22C3 and SP263 was independently evaluated by five pathologists, all certified PD-L1 trainers. The IC with SP142 was assessed by three of these pathologists, who have particular expertise in breast pathology. Following the computation of the intraclass correlation coefficient (ICC) for each assay and their respective thresholds, we assessed the agreement between different raters and assays using Fleiss's κ, with a 95 % confidence interval (CI).Overall, we observed a significant (p < 0.001) ICC with both CPS assays [22C3 = 0.939 (CI:0.913–0.96); SP263 = 0.972 (CI:0.96–0.982); combined 22C3-SP263 = 0.909 (CI:0.874–0.938)]. Fleiss's κ confirmed an almost perfect agreement among pathologists and assays: 22C3 = 0.938 (CI:0.857–1.018); SP263 = 0.972 (CI:0.890–1.052); combined 22C3-SP263 = 0.907 (CI:0.869–0.945). Perfect inter-rater agreement was reached considering IC.This study establishes the reliability of assessing CPS in mTNBC using either the 22C3 pharmDx, as employed in the KEYNOTE studies, or the VENTANA SP263 assay. Each assay must be used on its designated platform, namely the Dako for 22C3 pharmDx and the Ventana for VENTANA SP263. It is important to remark that CPS and IC identify different patient cohorts and, therefore, are not interchangeable.

The detection of PD-L1 expression on liquid-based cytology in pleural effusion of lung adenocarcinoma and its prognostic evaluation: Between paired liquid-based cytology and cell block samples.

Programmed death-ligand 1 (PD-L1) expression levels measured by immunohistochemistry have been proven to predict the outcome of immunotherapy in lung adenocarcinoma (LUAD). However, data on PD-L1 expression on liquid-based cytology (LBC) in malignant pleural effusion (MPE) is scarce. This study cohort included 60 cases with MPE suffering from LUAD. PD-L1 SP263 assay was used for immunocytochemistry (ICC) on LBC and matched cell block (CB) to validate ICC protocols on LBC slides. Clinical outcomes were analyzed based on immunotherapy and PD-L1 tumor proportion scores (TPS) on LBC slides and CBs. PD-L1 expression with TPS ≥1% was lower in LBCs than in CBs (33 of 60 [55.0%] vs. 35 of 60 [58.3%]; p = .687). Even with the TPS ≥50% threshold, PD-L1 expression was lower in LBCs (10 of 60 [16.7%] vs. 15 of 60 [25%]; p = .125). Epidermal growth factor receptor (EGFR) exon 20 mutation, tumor cell proportion, and pleural fluid neutrophil-to-lymphocyte ratio were related to PD-L1 expression on CBs (p = .013, p = 0.022, and p = .011), respectively. Patients with subsequent immune checkpoint inhibitor therapy remained a better prognostic in subgroups of PD-L1 positive expression on LBC slides (TPS ≥1%, p = .041). LBC specimens had comparable performance to CBs in PD-L1 assessment and predicting treatment response to PD-L1-defined therapy.

Role of PD-L1 SP263 Assay in Cancer Immunotherapy: A Comprehensive Review

Role of PD-L1 SP263 Assay in Cancer Immunotherapy: A Comprehensive Review