PD-L1 Testing Research Articles

A real-world study of PD-L1 testing patterns and PD-1/PD-L1 inhibitor therapy in patients with metastatic non-small cell lung cancer: An analysis of the Sotiria Hospital lung cancer registry

A real-world study of PD-L1 testing patterns and PD-1/PD-L1 inhibitor therapy in patients with metastatic non-small cell lung cancer: An analysis of the Sotiria Hospital lung cancer registry

Impact of a PD-L1 Learning Collaborative: outcomes from a mixed-methods evaluation

Abstract Introduction/Objective PD-L1 Immunohistochemistry testing is often required to determine eligibility for immune checkpoint inhibitor therapy. An ASCP PD-L1 Learning Collaborative (LC) was formed aiming to: 1) identify ways to streamline PD-L1 testing; 2) encourage members to locally implement changes; and 3) develop a resource guide for the community. Methods/Case Report The PD-L1 LC (n=38 pathologists and laboratory professionals) participated in 3 activities: 1) 4 meetings in which LC members discussed current literature and practice; 2) 3 30-minute on-demand, credit-bearing panel videos, in which selected LC members summarized the LC outputs and shared their experiences; and 3) a guide summarizing resources relevant to streamlining PD-L1 testing. The mixed-methods evaluation included: 1) five- minute surveys before (n=24), immediately after (n=11) and 7-months post-LC (n=17); 2) polling questions (2-4 per meeting); 3) semi-structured interviews (n=5). Quantitative data was analysed using descriptive and inferential analysis, qualitative data using a thematic analysis / inductive reasoning approach. Results (if a Case Study enter NA) Baseline data confirmed delays in testing caused by unstandardized PD-L1 testing processes and suboptimal confidence in PD-L1 validation and methodologies. Post-LC, members self-reported perceived increased knowledge and higher confidence levels regarding discussion of PD-L1 scientific evidence and best practices. At the 7-month follow-up, 59% of respondents reported at least one PD-L1-related practice change, with 29% of participants selecting:1) Improving protocols for specimen acquisition, handling, or processing; 2) Improving communication with multidisciplinary care team; 3) Optimizing biomarker testing workflows. Remaining suboptimal knowledge post-LC suggests need for further educational efforts. Participants identified “Tumor-specific considerations” as the main resource missing for PD-L1 testing. Conclusion A learning collaborative has shown impact in improving PD-L1 testing processes and related practices among a group of pathology professionals. The group successfully made available three panel videos and a resource guide, and PD-L1-related practice changes were reported. Future initiatives should address remaining gaps and develop tumor-specific PD-L1 testing considerations.

Can multiplexing Immunohistochemistry for PD-L1, CD68, and CD3 improve scoring for “Keytruda®” Indication?

Abstract Introduction/Objective FDA-approved companion diagnostics immunohistochemistry scoring for PD-L1 is essential for Keytruda ® treatment in patients with NSCLC. The challenge with PD-L1 testing alone is false positive PD-L1 expression score due to alveolar macrophage infiltration. Multiplexing with PD-L1, CD68, and CD3 could help alleviate this issue. By viewing PD-L1 expression on tumor cells, CD68 expression on macrophages, and the presence of CD3+ T cells on a single slide, pathologists will be able to see the presence of an immune microenvironment (high PD-L1 expression with abundant macrophages) and the potential for response to other types of Immunotherapies (presence of T cells). Methods/Case Report Positive NSCLC FFPE blocks were sectioned and stained using Agilent Dako Omnis. Two combinations of multiplex staining were prepared for each block by staining PD-L1 (brown) alone first followed by CD3 and CD68. First slide: CD3(Vina Green), CD68(Magenta); Second slide: CD3(Magenta), CD68(Vina Green). To prevent wash out, dehydration and clearing occurred with two changes of 100% alcohol and three changes of xylene for manual cover slipping. Results (if a Case Study enter NA) Manual scoring of PD-L1 alone vs two different multiplex combinations was compared to Agilent Proscia digital AI scoring using a preliminary study set (9 positives, 2 negatives). CD68-green and CD3-magenta showed better discrimination than CD68-magenta and CD3-green at a glance. This could be due to the staining intensity and nonspecific background staining of CD68-magenta. Manual scoring was higher compared to digital scoring, which could be due to the human error of positive bias. Digital scoring was significantly lower for PD-L1 alone vs both multiplex stains. The digital scoring for the multiplex stains showed a higher scoring percentage by removing false positive macrophages. Conclusion Reflex scoring workflow is being developed to focus on difficult cases using the multiplex triple stain, i.e. clear negative and clear >50% with 3+ intensity. More cases will be collected and studied to further investigate the improved PD-L1 scoring with digital imaging assisted by artificial intelligence and to compare the multiplex color combinations.

EP.17E.04 Cost-Effectiveness of PD-L1 Testing for Guiding Immunotherapy in Non-Small Cell Lung Cancer (Stage IIA-IIIB & Stage IV) Patients in China

EP.17E.04 Cost-Effectiveness of PD-L1 Testing for Guiding Immunotherapy in Non-Small Cell Lung Cancer (Stage IIA-IIIB & Stage IV) Patients in China

Brightfield Multiplex Immunohistochemistry Assay for PD-L1 Evaluation in Challenging Melanoma Samples.

Targeting the PD1/PD-L1 immune checkpoint pathway has rapidly become a therapeutic strategy for melanoma patients. Indeed, the quantification of PD-L1 expression by immunohistochemistry (IHC) in melanoma samples is already required, in some contexts, to allow access to anti-PD-1/PD-L1 immunotherapy. Despite a rising demand for PD-L1 testing, paralleling increasing cumulative experience in its assessment and quantification, it is fair to recognize that PD-L1 evaluation in melanoma samples still presents some critical issues. The aim of this technical report is to develop and validate a multiplex double staining protocol for PD-L1/SOX10 in Ventana Benchmark Ultra for routine practice. Our results show that double labeling provides the necessary tools to identify PD-L1 + melanoma cells clearly. The simultaneous visualization of 2 different proteins targets allows the topographical relationship between the 2 labeling to be evaluated within the context of the tissue morphology. Future studies are needed to test this technique's real-world applicability and effectiveness in implementing interpathologist agreement.

Effect on Non-Small Cell Lung Cancer after Combination of Driver Gene Mutations and Anti-PD-1/PD-L1 Immunotherapy as Well as Chemotherapy.

We aimed to reveal the correlation between pathological indicators and PD-L1, between gene mutation status in lung cancer through clinico-pathological data and lung cancer-related gene mutation and PD-L1 expression analysis. The study was conducted in Jinhua Municipal Central Hospital, Zhejiang, China from 2017 to 2022. PD-L1 testing and targeted gene mutations detection were evaluated. The clinical characteristics of these non-small cell lung cancer (NSCLC) samples have been obtained. The groups (LUAD, n=142; LUSC, n=143) were grouped according to clinico-pathological features and PD-L1 expression (Yes/No or High/Low), and the clinico-pathological and genetic and molecular features and correlation with PD-L1 expression were compared across the above groups. Comparisons and analyses were made between different treatment schemes. Lung adenocarcinoma (LUAD, n=142) and lung squamous carcinoma (LUSC, n=143) samples were enrolled (median age: 64 years old). Pleural invasion and M staging were significantly different from PD-L1 alterations (P<0.05). The percentage of patients with PD-L1 tumor proportion score (TPS)≥50% was 36.24% and the percentage of patients with PD-L1 TPS<50% was 29.53%. The percentage of patients with PD-L1 high-expressed and treated by immunotherapy was 75.93% and 63.41% experienced Partial Response/Complete Response. The mutations ratio of EGFR, ALK, KRAS, MET, RET and TP53 were 28.86%, 1.34%, 6.04%, 0.67%, 1.34% and 0.67%, respectively. KRAS mutation was significantly different from PD-L1 alterations (P<0.01). There are individual differences in PD-L1 expression, which can also vary depending on the different clinical features. Specific molecular features correlate with differential PD-L1 expression and may influence the response to therapy.

Clinicopathological factors of ovarian clear cell carcinoma: A single institutional analysis of 247 cases in China.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with a poor prognosis that often shows resistance to chemotherapy. This study retrospectively analyzed 247 patients with OCCC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) between August 2007 and August 2023. Univariate and multivariate Cox regression analyses were used to identify clinicopathological factors associated with OCCC, and a nomogram prediction model was developed to predict OCCC patient survival outcomes. Kaplan‒Meier survival analysis was used to compare survival outcomes among patients with recurrent disease. Compared with systemic therapy, secondary debulking surgery significantly improved the postrecurrence survival (PRS) rate (P = 0.006). Subgroup analysis revealed that the survival benefit was more pronounced in patients with recurrence and satisfactory tumor shrinkage (PPRS = 0.01, PPFS2 = 0.047). The multivariate analysis revealed that positive preoperative ascites, incomplete remission following initial treatment, and undergoing more than six cycles of postoperative chemotherapy were independent prognostic factors affecting overall survival (OS). Additionally, patients with a positive PD-L1 test who received immunotherapy did not experience relapse during the follow-up period. In conclusion, the secondary clearance procedure offers significant benefits for patients with recurrent OCCC, and patients may experience a survival benefit from supplemental immune or targeted therapy at the end of chemotherapy. The development of a personalized treatment plan can help achieve precise treatment, improve prognosis, and enhance patients' quality of life.

First-line (1L) anti-PD-1 plus chemotherapy in HER2-negative advanced gastric cancer: Real-world evidence from a single Korean center.

83 Background: The implementation of immune checkpoint inhibitor combinations as first-line (1L) treatment has shown promising outcomes and is now the standard of care for HER2-negative advanced gastric cancer. However, real-world evidence supporting this approach as 1L treatment remains limited. Here, we present an analysis of real-world outcomes, comparing 1L anti-PD-1 combined with doublet chemotherapy to the previous standard chemotherapy. Methods: Patient from January 2005 to August 2023 were retrospectively reviewed. The study defined the molecular epidemiology cohort (M cohort) as patients with results for HER2, Epstein-Barr virus (EBV), mismatch repair (MMR), or PD-L1. HER2-negative patients who received palliative first-line chemotherapy doublet regimens with or without PD-1 inhibitor were included. Survival analysis included progression-free survival (PFS) and overall survival (OS), as well as subgroup analyses for molecular subtypes. Results: Total 3,028 were enrolled in the M cohort. The incidence rates of HER2-positive, EBV-positive, and deficient Mismatch Repair (dMMR) were 20.0% (606/3028), 3.8% (93/2432), and 4.7% (126/2660), respectively. PD-L1 testing was conducted on 1,394 patients, with 54.3% (1634/3028) having a CPS (Combined Positive Score) of ≥10, and 47.6% (664/1394) having a CPS of ≥1. Among these patients 1,527 had received chemotherapy doublet, and 153 had received chemotherapy doublet with PD-1 inhibitor as their 1L treatment. During a median follow-up of 56.5 months (95% CI,49.9-66.2), patients who had received PD-1 inhibitor combination therapy showed improved PFS (7.1 vs. 6.1 months; Hazard Ratio [HR], 0.77; 95% Confidence Interval [CI], 0.64–0.93) and OS (18.1 vs. 14.6 months; HR 0.80; 95% CI, 0.63–1.01) compared to those without it. The benefits in PFS from PD-1 inhibitor combination therapy were particularly notable in patients with deficient MMR status (HR, 0.22 vs. 0.80 in those without PD-1 inhibitor combination; p for interaction &lt;0.05) and in patients with signet ring cell carcinoma histology (HR, 0.58 vs. 0.92 in those without PD-1 inhibitor combination; p for interaction &lt;0.05). Conclusions: We observed real-world efficacy of the combination of PD-1 inhibitor and chemotherapy doublet as 1L treatment for HER2-negative advanced gastric cancer, consistent with previous clinical trials. [Table: see text]

SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC.

TPS218 Background: Mutations in KRAS are among the most frequent oncogenic drivers with the G12C variant found in ~13% of NSCLC. Outcomes for KRAS G12C-mutant NSCLC may be improved by combining KRAS G12C inhibitors with current 1L standard of care (SOC). Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C, which delivers &gt;90% sustained target occupancy in preclinical models. In the LOXO-RAS-20001 phase 1/2 study, olomorasib in combination with pembrolizumab demonstrated preliminary efficacy and a favorable safety profile.1 Methods: SUNRAY-01 (NCT06119581) is a pivotal, global, phase 3 study in 1L advanced KRAS G12C-mutated NSCLC designed to seamlessly 1) optimize the dosing of olomorasib in combination with 1L SOC, and then 2) compare efficacy and safety of olomorasib plus SOC with placebo plus SOC. In the open-label randomized dose optimization (pembrolizumab plus olomorasib 50 mg vs 100 mg BID) and single arm safety lead-in (olomorasib plus pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before the phase 3 study (parts A and B) is opened for enrollment. In part A, 384 participants with PD-L1 expression ≥50% are randomized (1:1) to pembrolizumab plus olomorasib or placebo. In part B, 552 participants are randomized (1:1) to pembrolizumab, pemetrexed, platinum plus olomorasib or placebo regardless of PD-L1 expression. Allocation of participants with PD-L1 expression ≥50% to either part A or part B will be at the discretion of the investigator. The primary objective is to compare efficacy based on PFS per RECIST v1.1 by blinded independent central review. Secondary endpoints include OS, ORR, DOR, DCR, TTR, PFS2, safety and tolerability, and patient-reported outcomes. Eligible participants (≥18 years) must have a KRAS G12C mutation in tumor or blood and known PD-L1 expression (0-100%), stage IIIB, IIIC, or IV NSCLC not suitable for curative intent radical surgery or radiation therapy, measurable disease per RECIST v1.1, and an ECOG PS 0-1. Participants can be enrolled based on local KRAS and PD-L1 testing results. Participants should not have received prior systemic therapy for advanced or metastatic NSCLC, however 1 cycle of SOC treatment prior to enrollment is allowed if immediate treatment is clinically indicated. Participants with asymptomatic (lesions ≤1.5 cm) or previously treated radiographically stable brain metastases are eligible. Key exclusion criteria include history of pneumonitis/interstitial lung disease and clinically significant active cardiovascular disease or malabsorption syndrome. The study opened for enrollment in December 2023. Reference: 1. Murciano-Goroff et al. 2023 Cancer Res 83 (8 Suppl): CT028. Clinical trial information: NCT06119581 .

Muscle-invasive and metastatic urothelial carcinoma of the urinary bladder : Current state of histopathologic, molecular, and immunologic prognostic and predictive factors

Muscle-invasive and metastatic urothelial carcinoma (UC) represents aheterogeneous disease entity with numerous morphological, molecular, and immunological phenotypes. This article aims to provide an overview of current histopathological, molecular, and immunological prognostic and predictive factors in muscle-invasive and metastatic UC. Muscle-invasive and metastatic UC exhibits awide range of divergent differentiations and histological subtypes. The correct diagnosis of these morphological variants is essential, as they may determine the clinical course and may also present specific and potentially therapeutically targetable molecular alterations (e.g., HER2 alterations in micropapillary UC). The morphological subtypes largely correlate with the six molecular consensus subtypes. Furthermore, morphological and molecular subtypes are associated with immunological properties that are relevant for modern immunotherapies, such as the PD-L1 status. Numerous immunotherapy studies in the setting of curatively treatable muscle-invasive UC will be reported in 2024 and 2025, likely leading to an increasing number of PD-L1 testing indications.

Real-World Biomarker Test Ordering Practices in Non-Small Cell Lung Cancer: Interphysician Variation and Association With Clinical Outcomes.

Patients with metastatic or advanced non-small cell lung cancer (NSCLC) need biomarker testing, including, in most cases, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and PD-L1, to identify options for targeted therapies and to optimally incorporate immune checkpoint inhibitors into therapeutic regimens. We sought to examine real-world patterns of biomarker testing, quantify interphysician practice variation, and correlate testing with clinical outcomes. We extracted real-world data from a nationwide electronic health record-derived deidentified database from 17,165 patients diagnosed with advanced NSCLC between 2018 and 2021 and receiving care in the community setting. We analyzed data using descriptive analyses, fixed- and mixed-effects logistic regression models, and proportional hazard models. Only 67% of all 17,165 patients and 77% of patients with nonsquamous, metastatic NSCLC had ALK, EGFR, and PD-L1 testing within 90 days of diagnosis. Later diagnosis year (2019-2021 compared with 2018) was associated with higher rates of ALK, EGFR, and PD-L1 testing; stage IIIB/C disease (compared with stage IV), squamous histology, and Black or African American race were associated with lower rates. Interphysician variation was substantial with a median odds ratio between physicians (adjusted for patient factors) of 1.78 for ALK, EGFR, and PD-L1 testing. Patients with nonsquamous, metastatic NSCLC had significantly prolonged survival if tested with all three biomarkers (median, 364 days for all three v 180 for none of the three; hazard ratio, 0.67; P < .001). Rates of biomarker testing appear suboptimal with substantial interphysician variation. Testing correlates with improved survival, although causality cannot be proven from this study. Additional work is needed to address the underlying causes of suboptimal test ordering.

The influence of PD-L1 expression levels on the efficacy of combination therapy in thymic epithelial tumors.

The significant expression of PD-L1 in thymic epithelial tumors (TETs) has been confirmed, and immunotherapy and its combination therapy have been effective in TETs. However, there is no present evidence that the expression levels of PD-L1 affects the efficacy of combination therapy. Our study aimed to shed light on this relationship. Patients with thymic epithelial tumors (TETs) from multicenter hospitals were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) in 22 patients were included. We divided the patients the 22 patients with PD-L1 test into three levels (high expression, low expression and no expression) and analyzed the relationship between the levels of PD-L1 expression and the efficacy of combination therapy. Combination therapy showed an effective benefit in 22 patients with TETs, the median PFS (mPFS) was 16 months (95% CI: 8.5-23.5) and the median OS (mOS) was 38 months (95% CI: 21.5-54.5). Cox-regressive analysis found whether PD-L1 expression affected the PFS of patients (p = 0.017). Among the patients with PD-L1 expression, the levels of expression were correlated with curative effect (Kruskal-Wallis test, PFS: P = 0.012; OS: P = 0.01), and high expression group was along with better efficacy than low expression (Wilcoxon test, P = 0.01). Moreover, in 17 patients treated with immunotherapy combined with chemotherapy, the expression of PD-L1 was also associated with efficacy (Kruskal-Wallis test, p = 0.021). PD-L1 expression affects the PFS of patients. High expression of PD-L1 patients with TETs responded better to combination therapy, which could provide a therapeutic option in clinic. Besides, other targeted treatments should be considered.

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.

Comparison of treatment outcome between first-line combination immunotherapy (anti-PD-L1 or anti-PD1) with or without chemotherapy and chemotherapy alone in advanced non-small cell lung cancer patients in tertiary care hospital.

Despite promising outcomes of first-line immunotherapy with or without chemotherapy in advanced non-small cell lung cancer (NSCLC), limited accessibility due to reimbursement was remain the problem in low to middle income countries. This study aimed to evaluate real-world effectiveness of immunotherapy in patients with advanced NSCLC in Northern Thailand. A retrospective, single-centered cohort, was conducted. Patients with advanced NSCLC who underwent PD-L1 testing (excluding EGFR and ALK mutations) and were treated with immunotherapy or without chemotherapy or chemotherapy alone were included. The primary end point was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse events. A total of 123 patients, of which 21 patients received immunotherapy-based regimen and 102 patients received chemotherapy alone. The median PFS was 11.9 months in immunotherapy-based group compared to 5.93 months in the chemotherapy group, with a. hazard ratio (HR) of 0.4 (95% confidence interval [CI], 0.23 to 0.68; p = 0.001). Similarly, the median OS was 26.68 months in the immunotherapy-based group and 11.21 months in the chemotherapy group, with HR of 0.42 (95% CI 0.22-0.8; p = 0.009). ORRs were significantly higher in the immunotherapy-based group, with 65% of patients showing a response compared to 32% in the chemotherapy group (p = 0.006). The result of this real-world study in patients with advanced stage NSCLC indicate that first-line immunotherapy-based regimen was associated with significantly greater PFS, OS, and ORR with a safety profile consistent with pivotal studies.

PT35 Cost-Effectiveness Analysis of Nivolumab Versus Docetaxel for the Treatment of Advanced Nonsquamous NSCLC Including PD-L1 Testing in the United States

PT35 Cost-Effectiveness Analysis of Nivolumab Versus Docetaxel for the Treatment of Advanced Nonsquamous NSCLC Including PD-L1 Testing in the United States

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 .

Off-label use of checkpoint inhibitor (CPI) monotherapy in PD-L1–negative or unknown recurrent/metastatic head and neck cancer (R/M HNSCC).

6025 Background: The KN-048 study established that the CPI pembrolizumab with chemotherapy should be used for PD-L1 negative R/M HNSCC, while CPI monotherapy has limited efficacy (ORR 4%) in PD-L1 negative disease and should be reserved for PD-L1 positive disease. National patterns of PD-L1 testing and PD-L1 guided treatment selection are unknown. We examined PD-L1 testing rates, the use of CPI overall, and the use of CPI monotherapy in PD-L1 negative or unknown R/M HNSCC (“off-label”), and associated factors. Methods: This retrospective analysis included adult patients starting treatment for R/M HNSCC from 2019-2023 in the Flatiron Health electronic health record (EHR)-derived de-identified national database. Demographics, treatment type, and PD-L1 test results were summarized using descriptive statistics. Specifically, first-line therapy was categorized as CPI monotherapy, CPI with chemotherapy, or chemotherapy and/or cetuximab without CPI. “Off-label” use of CPI was defined as single-agent use without concurrent chemotherapy in patients with negative or unknown PD-L1. Factors associated with “off-label” use were identified using multivariable logistic regression analysis. Results: Our cohort included 3,395 patients with median age 66 (IQR 59-73), 65% White, 77% treated in a community setting, 76% with smoking history, 37% HPV positive, and 72% ECOG PS 0-1. Almost half of patients (44%) did not have a recorded PD-L1 test result; of those with known PD-L1 status (n=1886), distribution of combined positive score (CPS) 0, 1-19, and 20 was 19%, 41%, and 40%, respectively. The most common frontline treatment was CPI monotherapy (43%), followed by chemotherapy/cetuximab (33%) and CPI with chemotherapy (25%). CPI monotherapy use was highly prevalent in patients aged ≥75 (54%) and with ECOG PS ≥ 2 (52%). Among the subgroup of PD-L1 negative or unknown patients (n=1831), 37% (678) received CPI monotherapy (“off-label”). Factors associated with “off-label” CPI monotherapy use included ECOG PS ≥ 2 (OR 1.3), age ≥ 75 (OR 1.3), community practice (OR 1.7), and earlier year (HR 1.2) (all p&lt;0.05). Conclusions: Most US patients with R/M HNSCC are now receiving CPI-based therapy in the frontline setting, but PD-L1 testing rates remain suboptimal. Use of CPI monotherapy in PD-L1 negative or unknown HNSCC is common, particularly in elderly patients and those with poor performance status.[Table: see text]

PLWH and lung cancer: A single cancer center experience in Philadelphia, PA.

e20502 Background: Lung cancer has been identified as the leading cause of cancer-related deaths in people living with HIV (PLWH), and disproportionately affects this population independently of smoking status and CD4 count. At the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health, we serve a uniquely underserved patient population of PLWH. As PLWH were categorically excluded from most lung cancer clinical trials, we aim to study the clinical course of our patients with HIV and lung cancer. Methods: A retrospective review of 36 patients within SKCC at Jefferson Health in Philadelphia, PA from 2016 to 2023 were obtained utilizing ICD codes for lung cancer and HIV. Patients who were found to have HIV after their lung cancer diagnosis were excluded. Patient demographics, viral status, antiviral therapy, lung cancer stage, histology, molecular and fusion status, PD-L1 status, form of cancer-directed therapy, date of progression, last date of treatment, and date of death were recorded. Results: Of our 36 patients, 24 (66.7%) were male, and 20 (55.6%) racially identified as Black. 27 patients had NSCLC (20 with adenocarcinoma, 7 with squamous cell carcinoma), and 3 had SCLC. 24 (66.7%) patients had an undetectable viral load at the time of diagnosis and 35 (97.2%) were on antiviral therapy. 32 of 36 patients (88.9%) had advanced stage at the time of diagnosis; 11 had stage III disease (30.6%), and 21 (58.3%) had stage IV disease. Only 4 patients (11.1%) were diagnosed with stage I disease. The mean age of patients at diagnosis was 61.6 years (+/- 8.7 years). Of 18 patients with molecular testing performed, 4 had a KRAS mutation (22.2%) and 1 (5.6%) had a targetable EGFR mutation. Of 16 patients with PD-L1 testing, 7 (43.8%) had 0% expression, 8 (50%) had 1-49% expression, and 1 patient (6.2%) had PD-L1 expression &gt; 50%. The OS among this cohort was 1.3 years (95% CI: 0.8-3.8 years). Conclusions: Our cohort of patients demonstrated more advanced disease at presentation, a younger mean age at diagnosis and poor OS. These trends exist despite the majority of these patients having an undetectable HIV viral load at the time of diagnosis in the setting of ongoing antiviral therapy, indicating a potential relationship between even well-controlled HIV and aggressive lung cancer that warrants further exploration.

Biomarker testing in early-stage NSCLC: Results from the MYLUNG Consortium.

8047 Background: The Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium (MYLUNG) program seeks to identify and resolve barriers to biomarker testing in patients (pts) with non-small-cell lung cancer (NSCLC). We previously reported prospectively collected molecular testing data in pts with Stage IB-IV NSCLC (Evangelist et al. 2023). Herein we report additional data on molecular testing rates and patterns in the cohort of pts with early-stage (ES) NSCLC. Methods: Pts were enrolled from 12/20-9/22 at 18 community practices (76 sites) across the US Oncology Network. Analyses performed in the ES cohort include rates of molecular testing for targets with approved (PD-L1 , EGFR) or emerging ( ALK) therapies for ES NSCLC and next-generation sequencing (NGS); reasons for not testing; and treatment (Tx) received, including targeted therapy and immunotherapy (IO). Analyses are preliminary as data collection continues over 5-year follow-up. Results: Included in this analysis were 284 pts with newly diagnosed Stage IB-IIIA NSCLC: median age 68y (range 32, 92); 50% female; 54% ECOG 0-1; 61% adenocarcinoma, 36% squamous cell carcinoma. In total, 76% of pts (82% of pts with adenocarcinoma vs 67% with squamous cell carcinoma) had molecular testing ordered prior to or within 12 weeks of initiating first systemic therapy. Rates of testing (either alone or inclusive of other tests) were PD-L1 ,74%; EGFR,71%; ALK, 62%; EGFR + PD-L1, 61%. In total, 52% of pts had NGS testing; overall, 16% received no molecular testing. The most common reasons for not testing were patient and/or provider attitude/perception (34%) and insufficient tumor tissue (25%). Conclusions: New therapeutic options provide a catalyst to increase molecular testing in ES NSCLC. EGFR and PD-L1 testing are now standard for the management of these pts, with other biomarkers emerging. In this study, 54% of pts received testing for PD-L1, EGFR, and ALK, with additional therapy being offered in pts with biomarker-positive tumors; however, 16% still received no molecular testing at all. For pts with EGFRwt/PD-L1+ tumors, prescription of IO increased 1.8-fold post-adjuvant FDA approval. Data from this and future analyses will be used to implement interventions to improve molecular testing rates in NSCLC. [Table: see text]

CGP-based IO biomarker assessment and treatment utilization across a major US health system.

e23109 Background: Immune checkpoint inhibitors (IO) have become a powerful precision therapy option to treat advanced stage cancer with biomarkers such as PD-L1, tumor mutational burden (TMB), and microsatellite instability (MSI) associated with improved patient response rates. Despite this, many patients do not receive genomic testing for all IO biomarkers. Providence, a large US community health system, developed a pathologist-directed testing protocol where comprehensive genomic profiling (CGP) was routinely used at time of diagnosis for advanced cancer patients. Methods: Advanced cancer patients who received CGP (ProvSeq 523) and IHC testing for PD-L1 between 2019-2023 were included in the study. Patients were required to be treated at Providence and were assessed for presence of IO biomarkers and subsequent therapy selection. Real world data were curated from patient charts and genomic laboratory data by employing a novel natural-language processing (NLP) approach to accelerate abstraction. Results: The study included 2,502 patients (53% female, median age 68y, 83% white). Top 3 tumor types tested were lung (40%), colorectal (9%), and breast (8%). Overall, 58% (N = 1,455) of patients had presence of ≥1 IO biomarker, with 46% (N = 1,155) being PD-L1 positive, and 27% (N = 682) being TMB-H. In PD-L1 negative patients (N = 1,347; 54%), 300 (22%) were TMB-H and 18 (1%) were MSI-H. 53% (N = 767) of patients who harbored an actionable IO biomarker received IO-based therapy. Fewer patients with an IO biomarker received chemotherapy compared to patients without an IO biomarker (23% vs 35%, p &lt; 0.001). Patients who possessed ≥2 IO biomarkers received an IO precision therapy 68% of the time vs 47% in patients with 1 IO biomarker (p &lt; 0.001). In PD-L1 negative patients, 26% (N = 78) of TMB-H patients received IO monotherapy compared to 5% (N = 49) of TMB-L patients. Conclusions: IO biomarker presence is associated with increased precision therapy use. CGP identified many TMB-H patients for IO monotherapy that would have been missed with PD-L1 testing alone. More than half of patients eligible for IO therapy don’t receive it; ongoing analyses will evaluate the impact of pathology-directed reflex testing on IO as well as targeted therapy approaches. [Table: see text]