Purpose: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2–directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1–3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression. Patients and Methods: TROPHY-U-01 (NCT03547973) is an open-label phase II study that assessed the efficacy and safety of SG (alone or in combinations) in patients with unresectable locally advanced or metastatic UC (mUC). Archival tumor samples collected at enrollment for C1–3 were analyzed for Trop-2 membrane expression by considering histological scores (H-scores; scale 0–300) and the percentage of membrane positive tumor cells at low magnification (4×). The association of Trop-2 with clinical endpoints [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] was evaluated. Results: In C1–3, tissue was collected from 158 (82%) of 192 treated patients, and 146 (76%) had evaluable Trop-2 data. Trop-2 was highly expressed in tumor samples. The median [interquartile range (IQR)] Trop-2 H-score was 215 (180–246), and the median (IQR) percentage of membrane positive tumor cells was 91% (80–98). Trop-2 expression at any level was observed in 98% of patients. Furthermore, ORR, PFS, and OS benefits were observed across all Trop-2 expression levels. Conclusions: Trop-2 protein is highly expressed in UC, as confirmed by examining tumors from patients enrolled in the TROPHY-U-01 trial. The results indicate that SG demonstrates efficacy in mUC across Trop-2 expression levels.

Avelumab first-line maintenance (1LM) is approved for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who do not have disease progression after platinum-based chemotherapy (PBC). This retrospective study describes real-world treatment patterns and clinical outcomes in patients with la/mUC who initiated first-line (1L) systemic treatments, including avelumab 1LM, within iKnowMed, the US community oncology electronic health records database, between 1 December 2019 and 30 November 2023 and followed through 28 February 2024. In total, 1658 patients with la/mUC initiated 1L treatment: immuno-oncology (IO) monotherapy (41.2%), PBC only (32.4%), PBC followed by avelumab 1LM (11.2%), and other treatments (15.1%). The median OS (95% CI) from the start of 1L treatment was 20.4 (13.8, 30.0), 11.0 (8.5, 14.5), and 14.6 (12.6, 17.3) months for cisplatin-based only, carboplatin-based only, and IO monotherapy, respectively. Among the overall population, 36.1% and 11.8% of patients received second-line (2L) and third-line treatment, respectively. The median (95% CI) OS from the start of avelumab 1LM was 18.5 (13.8, 23.8) months. After discontinuation of avelumab 1LM, 43.5% received 2L treatment, and 59.3% of those received enfortumab vedotin (EV); the median (95% CI) OS from start of 2L EV was 12.7 (7.2, 16.5) months. Survival outcomes among patients treated with avelumab 1LM and 2L EV are consistent with respective clinical trials and other real-world studies.

Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved rapidly with the introduction of various immune-oncology (IO) agents and tyrosine kinase inhibitors (TKIs). We aimed to describe real-world treatment patterns and clinical outcomes of mRCC patients in post-IO and TKI settings. Methods: Using data from The US Oncology Network electronic health record database, iKnowMed, this retrospective cohort study included adult mRCC patients receiving subsequent treatments (index treatment) post-IO and TKI in combination or sequence between 1 January 2018 and 30 September 2020 and followed them until 30 April 2022. Treatment patterns were summarized descriptively. Overall survival (OS) and progression-free survival (PFS) from the index date was described using Kaplan–Meier analysis. Results: We identified 239 patients diagnosed with mRCC who received anticancer treatment post-IO and TKI therapies. The median age was 67 (range: 58, 73) years, 73.6% were male, and 61.5% had an intermediate/poor International Metastatic Renal Cell Carcinoma Database Consortium risk score. Among these, 29 (12.1%) received subsequent therapy at the line of therapy 2 (LOT2), 167 (69.8%) at LOT3, and 43 (18.0%) at LOT4+. The most common subsequent treatments were cabozantinib (38.5%) and axitinib (10.5%). The median OS for LOT2, LOT3, and LOT4+ was 18.0, 17.0, and 26.9 months, respectively. The median PFS for LOT2, LOT3, and LOT4+ was 6.1, 5.0, and 4.0 months, respectively. Conclusions: In mRCC patients treated with IO and TKI in combination/sequence, subsequent LOT choice is diverse, with TKI-based treatments being the most preferred. There is a need for considering treatment sequencing studies and studies with a new mode of action in this population.

Background/Objectives: Determining how a patient with metastatic cancer is responding to therapy can be difficult for medical oncologists, especially with text-only radiology reports. In this investigation, we assess the clinical usefulness of a new algorithm-based analysis that provides spatial location and quantification for each detected lesion region of interest (ROI) and compare it to information included in radiology reports in the United States. Methods: Treatment response radiology reports for FDG PET/CT scans were retrospectively gathered from 228 patients with metastatic cancers. Each radiology report was assessed for the presence of both qualitative and quantitative information. A subset of patients (N = 103) was further analyzed using an algorithm-based service that provides the clinician with comprehensive quantitative information, including change over time, of all detected ROI with visualization of anatomical location. For each patient, three medical oncologists from different practices independently rated the usefulness of the additional analysis overall and in four subcategories. Results: In the 228 radiology reports, quantitative information of size and uptake was provided for at least one lesion at one time point in 78% (size) and 95% (uptake) of patients. This information was reported for both analyzed time points (current scan and previous comparator) in 52% (size) and 66% (uptake) of patients. Only 7% of reports quantified the total number of lesions, and none of the reports quantified changes in all lesions for patients with more than a few lesions. In the assessment of the augmentative algorithm-based analysis, the majority of oncologists rated it as overall useful for 98% of patients (101/103). Within specific categories of use, the majority of oncologists voted to use it for making decisions regarding systemic therapy in 97% of patients, for targeted therapy decisions in 72% of patients, for spatial location information in 96% of patients, and for patient education purposes in 93% of patients. Conclusions: For patients with metastatic cancer, the algorithm-based analysis of all ROI would allow oncologists to better understand treatment response and support their work to more precisely optimize the patient’s therapy.