Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell transplant (HSCT) with high morbidity and mortality. The triad of endothelial cell activation, complement dysregulation, and microvascular hemolytic anemia has the potential to cause end organ dysfunction, multiple organ dysfunction syndrome and death, but clinical features mimic other disorders following HSCT, delaying diagnosis. Recent advances have implicated complement as a major contributor and the therapeutic potential of complement inhibition has been explored. Eculizumab has emerged as an effective therapy and narsoplimab (OMS721) has been granted priority review by the FDA. Large studies performed mostly in pediatric patients suggest that earlier recognition and treatment may lead to improved outcomes. Here we present a clinically focused summary of recently published literature and propose a diagnostic and treatment algorithm.

Triple-negative breast cancer is increasingly recognized as a heterogeneous entity that can be categorized according to histologic, molecular, and clinical subtypes. While chemotherapy remains the backbone of treatment for this disease, there are now several available targeted agents including immunotherapy, poly(adenosine diphosphate-ribose) polymerase inhibitors, and most recently a Food and Drug Administration–approved antibody-drug conjugate sacituzumab govitecan-hziy as a third-line treatment of metastatic triple-negative breast cancer. We review several actionable targets for triple-negative breast cancer and describe promising nonimmunotherapeutic agents including cyclin-dependent kinase inhibitors, androgen receptor inhibitors, mitogen-activated protein kinase inhibitors, phosphoinositide 3-kinase inhibitors, AKT (also known as protein kinase B) inhibitors, and antibody-drug conjugates.

1570 Background: The goal of phase 3 randomized clinical trials (RCTs) is to show clinically meaningful benefit for patients. An analysis of phase 3 RCTs presented at the ASCO 2022 Annual Meeting (ASCO22) was undertaken to assess which endpoints were evaluated. Methods: A systematic analysis was undertaken of ASCO22 abstracts from phase 3 RCTs reporting primary, secondary, interim, updated, and subgroup analyses, as well as trials reporting methodology of currently enrolling studies. Trials that reported posthoc, exploratory, biomarker, and retrospective analyses of RCTs were excluded. Information from ASCO22 materials and clinical trial registration websites was recorded by two independent researchers. Results: In total, 166 RCTs were identified: 93 trials with 50,781 enrolled patients and 73 trials expected to enroll 52,098 patients. More trials reported on patients with locally advanced/metastatic cancer (64.5%) compared to localized cancer (35.5%). Funding source was pharmaceutical or biotechnology company in 62%. Within locally advanced/metastatic trials, overall survival (OS) was a primary endpoint in 40%, while progression-free survival (PFS) was a primary or co-primary endpoint in 45% and 13% respectively. Other primary endpoints included (invasive) disease-free survival ((i)DFS), event free survival (EFS), overall response rate and pathological complete response. In trials that did not include OS as a primary endpoint, OS was a secondary endpoint in 88% (n = 56/64). Within the localized group, trials were subdivided into adjuvant, neo-adjuvant, definitive and other categories. Within the adjuvant trials (n = 27), the most common primary endpoint was (i)DFS (37%), followed by OS (15%). Other primary endpoints included recurrence-free survival, invasive breast cancer free survival, metastasis-free survival, EFS, and PFS. Across all trials, quality of life (QOL) was never reported as a primary endpoint, however it was as a secondary or other outcome in 53% for locally advanced/metastatic trials and 42% for localized trials. When comparing the endpoints reported in the ASCO22 abstract and meeting materials with those listed on the trial registration website, discordance was noted in 14%. Conclusions: Phase 3 RCTs presented at ASCO22 represented participation from over 100,000 patients, however, fewer than half in locally advanced/metastatic cancer and fewer than one quarter in localized disease utilized OS as a primary endpoint. QOL was listed as an endpoint in roughly one half of all trials. Endpoints reported did not match registration data in a significant minority. Debate over which endpoints should be used for cancer RCTs should be informed by this data.

Oral cyclin-dependent kinase (CDK) 4/6 inhibitors are routinely used to treat metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer in combination with endocrine therapy; however, they have not been widely used for other tumour types. Trilaciclib is an intravenous CDK 4/6 inhibitor that causes reversible cell cycle arrest in the G1 phase and transient haematopoietic stem and progenitor cell arrest. Ultimately, this protects the bone marrow and immune system from the cytotoxic impact of chemotherapy. Trilaciclib has been evaluated in extensive-stage small cell lung cancer in combination with chemotherapy as a myeloprotective agent and was approved by the US Food and Drug Administration for this use in February 2021. In metastatic triple-negative breast cancer, trilaciclib plus chemotherapy had a survival benefit over chemotherapy alone. This is being further investigated in a phase III trial. This review outlines the mechanism of this novel agent and describes preclinical and clinical data, characterizing its use in extensive-stage small cell lung cancer and advanced triple-negative breast cancer.

4052 Background: ASCC incidence is rising. There are limited data on the relationships between sociodemographic & clinicopathological features and outcomes of ASCC pts. Methods: Pts diagnosed with ASCC between 2004 and 2016 were retrospectively reviewed. Data obtained from the NCDB were used to examine the impact of sociodemographic status on clinicopathological features and outcomes. Pts were categorized based on low (median < $38,000) or high (≥$68,000) income and low ( > 21% with no high school diploma) or high ( < 7% with no high school diploma) education areas based on zip code at time of diagnosis. Logistic regression and chi-square were used to examine differences between groups. Results: In total, 44,084 pts with ASCC were identified: median age, 59 yrs, 86% white; 11% black; 64% female. Most pts (84%) resided in metro areas; 29.7% vs 19.8% lived in high vs low income areas; 22.9% vs 17.8% lived in high vs low education areas. Seven percent were uninsured, 50% had government (Gov), and 43% had private insurance. Male gender (HR 1.62, CI 1.41-1.85, p < 0.001), low income area (HR 1.28, CI 1.19-1.37, p = 0.014), and insurance status (Gov, HR 1.55, CI 1.32-1.82, p < 0.001 and uninsured, HR 1.37, CI 1.37-1.85, p = 0.039) were associated with a higher risk of death. After adjusting for age, sex, race, stage, grade, insurance status, and comorbidity, pts from low income/education (n = 6695) vs high income/education (n = 4316) areas had a 33 % increased risk of death (HR: 1.33, p < 0.001). Pts with stage IV ASCC in the low income/education (n = 227) vs high income/education (n = 295) groups had worse overall survival (mOS, 1.4 vs 1.9 yrs, p < 0.020). Of the 44,084 pts, 5461 (12.4%) had confirmed HPV status. Of these, 2658 (48.7%) were HPV+ (high risk subtypes) and 2803 (51.3%) were HPV-. Compared to the HPV- pts, HPV+ pts were more likely to be women (71.8% vs 67.8%, p = 0.001), have stage 3 (38.1% vs 33.6%) or 4 (7.9% vs 5.9%, p < 0.001) cancer, and have poorly differentiated (29.5% vs 25.6%, p < 0.001) tumors. There were no significant differences in race, education, income, metro area, insurance status, or comorbidity between the HPV+ and HPV- pts. Moreover, HPV status did not impact OS (HR 0.92, CI 0.81-1.04, p = 0.195). Conclusions: HPV status was not correlated to income, education or insurance status, and did not impact OS in ASCC pts. Male gender and insurance status were associated with increased risk of death. Pts living in low income and low education areas were associated with worse survival.