Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

BACKGROUND: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. MATERIALS AND METHODS: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. RESULTS: Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). CONCLUSION: OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Real-world outcomes among patients with HER2+ metastatic breast cancer with brain metastases.

BACKGROUND: Among patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC), incidence of brain metastases (BMs) is relatively high and increasing. Despite the high unmet need for patients with HER2+ MBC and BMs, real-world data on treatment patterns and outcomes for these patients are limited. OBJECTIVE: To compare treatment patterns and overall survival (OS) among patients with HER2+ MBC with and without BMs in the United States. METHODS: This was a real-world retrospective cohort study in which adults diagnosed with HER2+ MBC between January 1, 2016, and May 31, 2019, were identified in the Flatiron Health electronic health records database. The cohort was stratified by presence of BMs at MBC diagnosis (baseline) and before the initiation of each line of therapy (LOT). Key outcomes were OS and systemic therapy/regimen used within each LOT. An adjusted Cox proportional hazards model was used to evaluate the impact of BMs on OS. RESULTS: Of 1,755 included patients, 173 (9.9%) had BMs at baseline. Trastuzumab+ pertuzumab-based regimens were the most common first- (n = 689, 44.3%) and second-line (n = 316, 35.3%) treatments for all patients. Among patients with BMs, trastuzumab emtansine was the most common third-line regimen (n = 18, 23.4%). Lapatinib-based regimens were used more frequently among patients with BMs but were used by less than 20% of patients with BMs within any LOT. Median OS was 22.3 and 37.3 months for patients with and without BMs at baseline, respectively. Patients with BMs had a higher risk of death compared with patients without BMs (HR, 3.2; 95% CI = 2.6-3.8). CONCLUSIONS: BMs are associated with an increased risk of mortality among patients with HER2+ MBC. Further studies are needed to evaluate the extent to which novel systemic therapies for HER2+ MBC address the unmet need among patients with BMs. DISCLOSURES: This study was funded by Seagen Inc. Andres Forero-Torres is an employee of and owns stock in Seagen Inc. Kendra DeBusk is an employee of Seagen Inc. and owns stock in Seagen Inc. and Roche. Andy Surinach and Yutong Liu are employees of Genesis Research, which received funding from Seagen Inc. in connection with this study. At the time of this study, Chimeka Ike was an employee of Seagen Inc. and owns stock in Seagen Inc. At the time of this study, Nicolas Lindegger was an employee of Seagen Inc., Seagen International GmbH, and owns stock in Seagen Inc. and Roche. At the time of this study, Naomi Schwartz was a paid consultant to Seagen Inc.; she currently is an employee of and owns stock in Seagen Inc.

Efficacy of tucatinib for HER2-positive metastatic breast cancer after HER2-targeted therapy: a network meta-analysis.

Aim: A systematic literature review and network meta-analysis of randomized controlled trials in patients receiving therapy for HER2+ unresectable/metastatic breast cancer after ≥1 HER2-directed therapy was conducted to compare progression-free survival (PFS) and overall survival (OS). Methods: Hazard ratios (HRs) and relative differences from fractional polynomials (FPs) for PFS and OS were assessed by Bayesian network meta-analyses. Results: For PFS, surface under the cumulative rankogram (SUCRA) ranked tucatinib plus trastuzumab with capecitabine as highest in both HR and FP analyses, followed by T-DM1 monotherapy and neratinib plus capecitabine. For OS, SUCRA ranked tucatinib plus trastuzumab with capecitabine as highest in both HR and FP analyses, followed by pertuzumab plus trastuzumab with capecitabine and T-DM1 monotherapy, with similar scores. Conclusion: Tucatinib plus trastuzumab with capecitabine, and T-DM1 monotherapy, consistently showed improved PFS and OS versus lapatinib/trastuzumab plus capecitabine and non-targeted treatments.

Lay abstract Although several therapies are used in HER2-positive metastatic breast cancer, direct head-to-head comparisons of these therapies are lacking. We conducted a network meta-analysis, a way of indirectly comparing the results of different clinical trials, to compare how long patients receiving therapy had no disease progression, and also how long patients survived. In terms of avoiding disease progression, tucatinib plus trastuzumab with capecitabine ranked highest, followed by T-DM1 monotherapy and neratinib plus capecitabine. In terms of survival, tucatinib plus trastuzumab with capecitabine ranked highest, followed by pertuzumab plus trastuzumab with capecitabine and T-DM1. Tucatinib in combination with trastuzumab plus capecitabine and also T-DM1 monotherapy consistently demonstrated improved progression-free and overall survival outcomes compared with other therapies.

Molecular Targets and Emerging Therapeutic Options for Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is an aggressive malignancy characterized by its early metastasis, high rates of recurrence, and poor prognosis. Multiple obstacles complicate the clinical management of uLMS. These include the fact that most uLMS are typically identified only after a woman has undergone hysterectomy or myomectomy, the limited efficacy of adjuvant therapy for early stage disease, and the poor response of metastatic disease to current treatments. Here, we discuss recent insights into the molecular basis of uLMS and discuss emerging options for its clinical management. Particular attention is given to the biologic basis of these strategies with the goal of understanding the rationale motivating their use.