Sacituzumab Govitecan Research Articles

Therapeutic strategies for metaplastic breast cancer: A clinicopathologic analysis of a single institution cohort.

e13128 Background: Metaplastic breast cancer (MpBC) is a rare, aggressive, and histologically diverse subtype, which is associated with worse survival outcomes than other triple-negative breast cancers. Methods: This study is a single-institution retrospective analysis of 30 patients with MpBC, focused on response to therapies in the context of histologic subtype, molecular alterations, and PD-L1 expression. Patients with MpBC who received treatment at our institution consented to share clinical information with a research biorepository. Clinicopathologic and next generation sequencing (NGS) data were obtained from patients’ electronic health records. The primary outcomes are overall survival (OS) and event-free survival (EFS), and the secondary outcomes are responses to neoadjuvant therapy, tumor growth on taxane and/or anthracycline, and responses to systemic therapy in the relapsed/metastatic setting. Results: Among the 30 MpBC patients, the median age at diagnosis was 47.5 years. 86.7% were diagnosed with early-stage disease, 36.7% with squamous cell MpBC, 93.3% with triple-negative disease, and 30% with HER2-low disease. Of the patients diagnosed with early-stage disease, 88.5% received neoadjuvant systemic therapy, 96.2% underwent breast surgery, 92.3% received definitive/adjuvant radiation, and 76.9% received adjuvant systemic therapy. 61.5% of patients with localized disease experienced local and/or distant relapse. Median EFS was 14.0 months (95% CI, 10 to 20 months). Median OS was 26.5 months (95% CI, 20 to 32 months). There was no clearly superior neoadjuvant regimen based on MpBC subtype, but more patients with squamous MpBC experienced tumor growth on taxane-containing therapy compared to those with growth on anthracycline-containing regimens. In the relapsed/metastatic setting, patients with squamous cell MpBC and somatic mutations in the PI3K/Akt/mTOR pathway had prolonged partial responses to combination treatment with an anthracycline, mTOR inhibitor, and VEGF inhibitor. Median treatment duration with sacituzumab govitecan in the 1st or 2nd line metastatic setting was 1.5 months (95% CI, 1 to 4 months) before disease progression. Low tumor mutational burden was seen across all MpBC subtypes (median 2.1, 95% CI 1.6-4.0). 75% of the cases were PD-L1 positive by Immune Cell expression. There was no clear association between PD-L1 expression and response to immunotherapy-containing treatments in the neoadjuvant or relapsed/metastatic setting. Conclusions: Our findings on the presentation of MpBC correlate with other clinicopathologic studies. For squamous MpBC, we noted trends on the utility of anthracycline-containing regimens. Chemoimmunotherapy and antibody-drug conjugates have changed management of triple-negative and HER2-low breast cancer, but more prospective data are needed to determine the optimal therapeutic strategies for MpBC.

Biology and performance of pre- and post-pembrolizumab (pembro) vesical imaging–reporting and data system (VI-RADS) to predict the pathological response in muscle-invasive urothelial bladder cancer (MIBC): Full data analysis from a clinical trials pipeline.

4591 Background: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to predict the probability of MIBC. It has been also used in studies using standard neoadjuvant chemotherapy. No studies have analyzed the performance of VI-RADS to predict the pT0 or pT≤1 response post-immunotherapy (IO) in MIBC. Methods: In PURE-01 study patients (pts) were staged with mpMRI before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VI-RADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0=no evidence of disease) and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) studies. Transcriptome-wide expression profiling was matched with VI-RADS scores. Results: In PURE-01, 115 pts had centrally-reviewed MRI scans (N=230 mpMRI), treated between 02/17 and 08/18. In total, 32 (27.8%) had pure/predominant non-urothelial carcinoma (UC) histology, 54 (47%) had a cT3-4N0 MIBC. Pre-pembro: 21 pts (18.3%) had no measurable disease (VI-RADS=0), 37 (32.2%) a VI-RADS 1-3 score, and 57 (49.5%) had a VI-RADS 4-5 score. 20 pts (17.4%) had a downstage from VI-RADS 4-5 to VIRADS 0-3 post-pembro. Pre-pembro VIRADS 4-5 were associated with higher angiogenesis and epithelial-mesenchymal transition (EMT) activity vs VI-RADS 0-3 (p=0.011 and 0.033). Both pre-pembro and post-pembro VI-RADS 0-3 scores were the only significant covariates against pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VI-RADS 0-3 against pT≤1 response (OR: 23.4, 95%CI: 7-95.3, p<0.0001). The AUC of this model was 0.90. Model-based decisions were supported in the range of threshold probabilities of 10-80%. Post-pembro VI-RADS 4-5 were characterized by higher stromal signature scores vs VI-RADS 0-3. When post-therapy VI-RADS were tested in evaluable pts from the combined NureCombo+SURE-01 cohort (N=17pts, 34 mpMRI): 90% of post-VI-RADS 0-3 revealed a pT≤1 stage at radical cystectomy. Conclusions: VI-RADS scores mirrored distinct biological features in MIBC, recapitulating tissue biomarkers of IO response. VI-RADS scores post-IO revealed a strong association with pathological downstaging and represented a robust feature based on which selecting pts for bladder-sparing strategies. Results seemed to be also applicable to other novel neoadjuvant therapies beyond IO monotherapy. Clinical trial information: NCT02736266 .

Sequential use of antibody-drug conjugate after antibody-drug conjugate for patients with metastatic breast cancer: ADC after ADC (A3) study.

1022 Background: Optimizing sequential use of Antibody Drug Conjugates (ADCs) is an area of unmet need and of rising clinical importance. With the recent approvals of sacituzumab govitecan (SG) for HR+/HER2- and triple negative metastatic breast cancer (MBC) as well as trastuzumab deruxtecan (T-DXd) for HER2-low MBC, many patients are now candidates for multiple ADCs. However, given potential cross-resistance based on antibody target vs payload (Coates et al, Cancer Discov. 2021), optimal sequencing remains uncertain. We evaluated the safety and efficacy of ADC after ADC for patients with HER2 negative MBC. Methods: We included all patients at an academic institution treated with more than one ADC for MBC. Each line of ADC beyond the first was evaluated for presence of the same “antibody target” or “payload” compared to prior ADC. Clinicopathological information was gathered by chart review. We defined “cross-resistance” as progressive disease (PD) at time of first restaging on second ADC. Progression-free survival (PFS) was evaluated as time from start of treatment to disease progression or death from any cause. All PFS estimation was done using the KM method. All pairwise comparisons across ADC were done using a Wilcoxon Rank Sum test to allow for divergences from normality in progression times. Significance was declared as a type I error less than 0.05. Results: A total of 193 patients with MBC were treated with ADCs between August 2014-February 2023. Among these,32 patients were identified as having received more than one ADC (HR+/HER2- = 13, TNBC = 19, HER2 low = 22). Median age at time of second ADC was 57.1 years (range 31.3-88.6) and patients had received a median of 4 lines (range 2-12) of prior treatment before initiation of second ADC. The median PFS on the first ADC used (ADC1) was significantly longer at 7.55 months (95% CI 3.22-10.25) compared to a median of 2.53 months on the second ADC (ADC2) (95% CI 1.38-4.14) (p=0.006). PFS for ADC2 with antibody target change was 3.25 months (95% CI 1.38 months, n/a) compared to 2.30 months with no target change (95% CI 1.38 months, n/a) (p=0.16). At time of first imaging, cross-resistance was present in 17 cases (53.1%), absent in 12 (37.5%), and not evaluable in 3 cases. When the second ADC contained the same antibody target as the first, cross-resistance was present in 9/13 cases (69.2%), compared to 8/16 cases (50.0%) when the second ADC targeted a different tumor antigen. Similarly, differences were noted based on payload switch vs not. Conclusions: This study highlights a subset that had cross-resistance to ADC after ADC, while others had durable responses on latter lines of therapy, particularly if a different antibody target was utilized. Further research is needed to validate these findings and discern mechanisms of clinical resistance to guide optimal sequencing of ADC-based treatment options.

A phase 2 randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): ELEVATE-TNBC.

TPS1130 Background: Improving outcomes in patients (pts) with TNBC remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) is approved for newly diagnosed pts with PD-L1+ tumors. Further, single-agent sacituzumab govitecan (SG), a Trop-2–directed antibody-drug conjugate, is approved for pts with mTNBC who received ≥2 prior systemic therapies (≥1 for metastatic disease). However, more options are needed for pts with PD-L1–negative mTNBC and for those with disease progression on chemo ± ICI. Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal often overexpressed on TNBC cells. Magrolimab blockade of CD47 induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemos, including taxanes, enhance prophagocytic signals on tumor cells, which may lead to synergistic antitumor activity with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab + nab-paclitaxel/paclitaxel or + SG in mTNBC. Methods: This open-label study has 2 cohorts (C) with safety run-in and phase (ph) 2 portions. Eligible pts are ≥18 y with measurable disease per RECIST 1.1. C1 pts have PD-L1–negative untreated mTNBC. C2 pts have mTNBC and received 1 prior line of therapy in the advanced setting, a taxane in the neoadjuvant/adjuvant or metastatic setting, and, if PD-L1+, an ICI. Exclusion criteria include active central nervous system disease, RBC transfusion dependence, and prior treatment with CD47/SIRPα-targeting agents. C1 assesses nab-paclitaxel/paclitaxel + magrolimab (safety run-in) or ± magrolimab (ph 2; randomized 1:1). C2 assesses magrolimab + SG (safety run-in and ph 2). In C1 safety run-in, magrolimab is given intravenously (IV) as a 1-mg/kg priming dose on day (D) 1 of cycle 1 to mitigate on-target anemia, followed by 30 mg/kg (cycle 1: D8, 15, 22; cycle 2: D1, 8, 15, 22; cycle 3+: D1, 15) (28-d cycles). In C2 safety run-in, pts receive a 1-mg/kg priming dose on D1, followed by 30 mg/kg (cycle 1: D8, 15; cycle 2: D1, 8, 15) and 60 mg/kg (cycle 3+: D1) (21-d cycles). The recommended ph 2 dose (RP2D) is determined in the safety run-in, with de-escalation if prespecified dose-limiting toxicity (DLT) criteria are met. Once RP2D is determined, the ph 2 cohorts will follow their respective dose schedules. Nab-paclitaxel/paclitaxel and SG are given IV per standard of care. The primary endpoints are incidence of DLTs, adverse events, and abnormal lab results by CTCAE v5.0 (safety run-in); progression-free survival by RECIST 1.1 (ph 2 C1); and confirmed objective response rate by RECIST 1.1 (C2; pooled safety run-in and ph 2). Planned enrollment is ≈144 pts. Clinical trial information: NCT04958785 .

Antibody-Drug Conjugates in the Treatment of Urothelial Cancer.

Antibody-drug conjugates (ADCs) have transformed the treatment landscape in oncology and become an essential therapeutic modality. In urothelial carcinoma (UC), the two ADCs that have been especially successful in clinical practice are enfortumab vedotin and sacituzumab govitecan. These drugs are currently approved as monotherapy for later lines of treatment in locally advanced or metastatic UC and have had a significant impact for patients with limited treatment options. Combinational trials, as well as additional ADCs, are currently being investigated in the treatment of UC for subsequent lines of therapy as overall survival rates remain dismal.

Metastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study

BackgroundNectin-4 and Trop-2 are transmembrane targets of FDA-approved antibody-drug conjugates (ADC) Enfortumab-vedotin (EV) and Sacituzumab govitecan (SG), respectively, for the treatment of metastatic urothelial carcinoma (mUC). The expression and role of Nectin-4 and Trop-2 in mUC variant histology is poorly described. Materials and MethodsWe evaluate membranous and cytoplasmic protein expression, and mRNA levels of Nectin-4 and Trop-2 within matched primary and metastatic mUC samples to determine heterogeneity of ADC targets in mUC variants. ResultsPatients with mUC were consented for rapid autopsy immediately after death. Tissues from matched primary and metastatic lesions were collected. A total of 67 specimens from 20 patients were analyzed: 27 were UC, 17 plasmacytoid (PUC), 18 UC with squamous differentiation (UCSD), and 5 neuroendocrine (NE); 10 from primary and 57 from metastatic sites. All histology except NE expressed moderate-high levels of Nectin-4 and Trop-2 by both immunohistochemistry and RNAseq. Nectin-4 demonstrated prominent cytoplasmic staining in metastatic PUC and UCSD. Trop-2 demonstrated strong cytoplasmic and membrane staining in primary and metastatic tumors. Interestingly, Nectin-4 and Trop-2 expression are positively correlated at both mRNA and protein levels. ConclusionUC and non-NE variants express notable level of Nectin-4 and Trop-2 in both primary and metastatic lesions. Membrane staining of Nectin-4 and Trop-2 is present but cytoplasmic staining is a more common event in both mUC and mUC variant histology. These findings support evaluation of EV and SG in heavily treated variant histology BC and urge attention on the clinical relevance of cytoplasmic localization of ADC targets.

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.

The efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States. We performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). SG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be cost-effective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY. From a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The cost-effectiveness of SG can be improved if the price is substantially reduced.

Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.

Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels. Treatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non-small cell lung cancer. ADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors. See related commentary by Berg and Choudhury, p. 3557.

Advances in the Management of Metastatic Breast Cancer

Recent advances in the understanding of the molecular underpinnings of metastatic breast cancer have led to the identification of novel therapeutic targets. The latest update to the NCCN Guidelines for Breast Cancer reflects a rapidly evolving treatment landscape, highlighting the growing importance of combination therapies and personalized medicine in managing estrogen-receptor (ER)–positive, HER2-positive, and triple-negative subtypes. For patients with ER-positive disease, the standard of care remains combination therapies involving cyclin-dependent kinase 4/6 inhibitors, endocrine therapy, and PI3 kinase. In patients with HER2-positive disease, the use of fam-trastuzumab deruxtecan-nxki and tucatinib have demonstrated improved outcomes. For those with triple-negative breast cancer, pembrolizumab, PARP inhibitors, and antibody–drug conjugates (eg, sacituzumab govitecan-hziy) have shown activity.

Antibody-drug Conjugates for Breast Cancer Treatment.

The use of antibody-drug conjugates is expected to transform the management of human malignancy. Antibody-drug conjugates for cancer treatment are designed to deliver anticancer drugs to tumor cells. The main components of such conjugates are a monoclonal antibody that binds to a tumor antigen, an anticancer drug to inhibit tumor cell growth and a linker that serves to conjugate the antibody and drug. The antibody-drug conjugates developed and approved for breast cancer treatment are ado-trastuzumab emtansine, (fam)-trastuzumab deruxtecan-nxki and sacituzumab govitecan. The mechanisms of action, clinical uses and toxic effects of these antibody-drug conjugates are discussed.

Emerging Therapies in the Treatment of Bladder Cancer

The advent of targeted agents, such as enfortumab vedotin, erdafitinib, and sacituzumab govitecan, have revolutionized the treatment of metastatic urothelial cancer. Although these novel therapies have demonstrated favorable efficacy outcomes, their toxicity must be carefully monitored. The NCCN Guidelines for Bladder Cancer recommend platinum-based chemotherapy in this clinical context, but the combination of targeted and immunotherapeutic agents may have the potential to replace it as frontline standard of care.

201P Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Preliminary phase II results

201P Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Preliminary phase II results

198P Relationship of diarrhea and neutropenia events with outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG): Post hoc analysis from the phase III ASCENT study

198P Relationship of diarrhea and neutropenia events with outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG): Post hoc analysis from the phase III ASCENT study

258TiP A phase II trial of loperamide (L) and granulocyte colony-stimulating factors (G-CSF) to improve sacituzumab govitecan (SG) tolerance in patients (pts) with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): PRIMED

258TiP A phase II trial of loperamide (L) and granulocyte colony-stimulating factors (G-CSF) to improve sacituzumab govitecan (SG) tolerance in patients (pts) with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): PRIMED

194P Safety outcomes by UGT1A1 status in the phase III TROPiCS-02 study of sacituzumab govitecan (SG) in HR+/HER2– metastatic breast cancer (mBC)

194P Safety outcomes by UGT1A1 status in the phase III TROPiCS-02 study of sacituzumab govitecan (SG) in HR+/HER2– metastatic breast cancer (mBC)

Rise of Antibody-Drug Conjugates: The Present and Future.

Antibody-drug conjugates (ADCs) embody a simple, but elegant, vision for cancer therapy-the delivery of a potent cytotoxic agent to tumor cells with minimal damage to normal cells-so-called smart chemo. Although there were significant challenges in achieving this milestone culminating in the first Food and Drug Administration approval in 2000, subsequent advancements in technology have led to rapid drug development with regulatory approvals for ADCs targeting a variety of tumor types. The most successful application for solid tumors has been in breast cancer, with ADCs becoming the standard of care across traditional human epidermal growth factor receptor 2 (HER2)+, hormone receptor+ (HR+) and triple-negative disease subtypes. Moreover, the improved features and gains in potency with the development of ADCs have expanded the treatment-eligible population to those with low/heterogeneous expression of the target antigen on the tumor with trastuzumab deruxtecan or in the case of sacituzumab govitecan, agnostic to target expression. Despite their antibody-directed homing, these novel agents come with their share of toxicities obligating appropriate patient selection and vigilant monitoring while on treatment. As more ADCs are included in the treatment armamentarium, mechanisms of resistance need to be studied and understood for optimal sequencing. Modifying the payload to use immune-stimulating agents or combination therapies with immunotherapy and other effective targeted therapies may further extend the utility of these agents in the treatment of solid tumors.

232P Real-world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom

232P Real-world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom

216P Sacituzumab govitecan in metastatic triple-negative breast cancer: Efficacy -with a focus on brain metastases- and toxicity in a real-world cohort

216P Sacituzumab govitecan in metastatic triple-negative breast cancer: Efficacy -with a focus on brain metastases- and toxicity in a real-world cohort

'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review.

Antibody-Drug conjugates (ADCs) are a relatively new class of drugs with a promise to improve the outcomes in specific cancers. By delivering the cytotoxic agent to tumor cells expressing specific antigens, ADCs achieve a better therapeutic index and more potency. ADCs have been approved for several hematological and solid malignancies, including breast, urothelial and gastric carcinoma. Recently, trastuzumab deruxtecan (TDXd) was the first ADC approved for previously treated metastatic HER2-mutant non-small cell lung cancer (NSCLC). Many promising ADCs are in the pipeline for clinical development in non-small cell lung cancer, including sacituzumab govitecan, patritumab deruxtecan, datopotamab deruxtecan and tusamitamab ravtansine. There is a hope that these drugs would cater to the unmet need of specific patient populations, including patients with currently untargetable mutations. We hope these drugs, e.g., TROP2 targeted ADCs, will also give more options for therapy in NSCLC to improve outcomes for patients. In this comprehensive review, we will be discussing the recent evidence including targets, efficacy and the safety of newer ADC candidates in NSCLC. We will also briefly discuss the specific toxicities, novel biomarkers, overcoming resistance mechanisms, challenges and the way forward, as these new ADCs and combinations find a way into the clinical practice.

TROP-2 is widely expressed in vulvar squamous cell carcinoma and represents a potential new therapeutic target.

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Etiologically, HPV-dependent and HPV-independent VSCC are distinguished. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Research has identified trophoblast cell surface antigen 2 (TROP-2) to be broadly expressed across different tumor entities. The aim of the present study was to systematically investigate the expression of TROP-2 in VSCC. TROP-2 protein expression was investigated by immunohistochemistry in a cohort comprising n = 103 patients with primary VSCC. A four-tier scoring system (0: no staining, 1 + : low staining, 2 + : moderate staining, 3 + : high staining) was applied for quantification of protein expression. For further analyses, two groups (low TROP-2 expression: 0/1 + ; high TROP-2 expression: 2 + /3 +) were generated. The entire study cohort, as well as HPV-dependent and HPV-independent VSCC were considered separately. In the entire VSCC study cohort, TROP-2 expression was present in 97.1% of all cases (n = 100) with 74.8% displaying high TROP-2 expression (2 + /3 +). Only 2.9% of tumors showed absent TROP-2 expression. Of note, all HPV-dependent VSCC (n = 18) demonstrated high TROP-2 expression (2 + /3 +). In the subgroup of HPV-independent VSCC (n = 70), high TROP-2 expression was associated with favorable clinical outcomes based on log rank test and univariate cox analysis. TROP-2 protein expression is of prognostic value in HPV-independent VSCC. The broad expression of TROP-2 in VSCC indicates the TROP-2 directed ADC Sacituzumab govitecan as a potential new therapeutic strategy for VSCC patients.