Overall Survival and Prognostic Factors in Metastatic Triple-Negative Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). METHODS: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. RESULTS: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. CONCLUSIONS: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

A Review of the Current FDA-Approved Antibody-Drug Conjugates: Landmark Clinical Trials and Indications.

Despite considerable treatment progress, cancer remains among the leading causes of death worldwide. Antibody-drug conjugates (ADCs), a rapidly growing class of systemic therapy, show promise by combining the properties of conventional chemotherapy and targeted therapy. Antibody-drug conjugates have been shown to be more efficacious than traditional chemotherapy. To date, there are 13 ADCs approved by the United States Food and Drug Administration (FDA) for treating various hematological and solid organ cancers. There are several new promising ADCs that are being developed and are in clinical trials. This review provides an overview of the current FDA-approved ADCs, the landmark clinical trials that led to their approval, the common toxicities seen in the landmark trials, the challenges associated with ADCs, and the potential future directions.

A retrospective analysis of immune checkpoint inhibitors in patients with preexisting organ dysfunction.

BACKGROUND: There are limited to no data regarding the use of immune checkpoint inhibitors (ICIs) in patients who have preexisting organ dysfunction because these patients are frequently excluded from clinical trials. The authors' objective was to evaluate the effects of ICIs in patients with chronic kidney disease (CKD), cirrhosis, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). METHODS: Data were obtained retrospectively for patients older than 18 years with solid organ malignancies who received at least one dose of an ICI between January 1, 2015, and January 1, 2021, and had either CKD (n = 90), cirrhosis (n = 20), COPD (n = 142), or CHF (n = 82) before ICI initiation at the authors' institution. Descriptive statistics were used to summarize patient characteristics, treatment characteristics, immune-related adverse events (IrAEs), and outcomes. An independent samples t-test or the Wilcoxon rank-sum test was used to assess differences in continuous variables; the χ2 test or the Fisher exact test was used to assess differences in categorical variables between patients with and without IrAEs. Progression-free survival (PFS) was assessed using Kaplan-Meier curves, and the log-rank test was used to assess differences in PFS. RESULTS: In all four cohorts, there were no statistically significant differences in patient characteristics, treatment characteristics, or outcomes, such as the number of hospitalizations and PFS, among those who experienced IrAEs compared with those who did not. In the CKD cohort, patients with IrAEs were significantly less likely to die than those without IrAEs (52% vs. 81% [p = .009] for all patients; 53% vs. 83% [p = .008] for patients with stage II/III disease who received no definitive local treatment and patients with stage IV disease); this difference was not observed in the cirrhosis, COPD, or CHF cohorts. There was no statistically significant difference in the number of heart failure and COPD exacerbations during the receipt of ICIs in the CHF and COPD cohorts, respectively. The incidence and time to onset of IrAEs in this study appeared to be similar to those reported previously in clinical trials that excluded patients with significant comorbidities. CONCLUSIONS: The current results demonstrate that ICIs are well tolerated by patients who have preexisting organ dysfunction.

Colon Cancer Survivorship in Patients Who Have Received Adjuvant Chemotherapy.

The number of colon cancer survivors in the United States is increasing due to improved early detection, better treatments that extend survival, and the growing aging population who are at high risk for cancer. Following initial active treatment, colon cancer survivors experience a wide range of long-term physical, psychological, and socio-economic effects that impact their overall well-being. Healthcare providers caring for survivors need to prioritize not only monitoring for cancer recurrence but also optimizing their overall health through addressing these long-term effects; managing their comorbidities; promoting healthy behaviors (like exercise, nutrition, and weight loss); and screening for a second primary cancer depending on their risk. Personalized survivorship care plans should be formulated clearly outlining the roles of various healthcare providers involved in their care. Our review article focuses on these various aspects of colon cancer survivorship, including surveillance for cancer recurrence specific to those who received adjuvant chemotherapy with curative intent.

Relapsed or Refractory Diffuse Large B-Cell Lymphoma: "Dazed and Confused".

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Approximately 30% to 40% of patients will develop relapsed/refractory (R/R) DLBCL, leading to significant morbidity and mortality. Salvage chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell rescue (HDT-ASCR) is the standard of care for chemosensitive and transplant-eligible R/R DLBCL. In patients who are ineligible for HDT-ASCR or who fail HDT-ASCR, treatment is mostly with palliative intent. However, the recent advances with chimeric antigen receptor T-cell (CAR-T) therapy and several FDA-approved targeted agents are changing the current landscape of R/R DLBCL management. There is no one-size-fits-all approach, and guidance regarding optimal sequencing of subsequent therapies is an unmet need. This review highlights the approved CAR-T constructs, including their efficacy, adverse effects, and real-world data; bridging therapy to CAR-T; the role of emerging targeted agents, including bispecific antibodies; and the timing of these targeted agents in relation to CAR-T therapy. Providing individualized treatment with thoughtful sequencing of available agents is essential until future prospective randomized clinical trials provide more insights.

Cerebral Venous Sinus Thrombosis due to Thrombosis with Thrombocytopenia Syndrome Following Ad26.COV2.S: A First Real-World Case Report of a Male Subject.

Thrombosis with Thrombocytopenia Syndrome (TTS) or Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) had been reported in patients receiving the Ad26.COV2.S vaccination (Johnson & Johnson [J&J]/Janssen) vaccine. They frequently presented with cerebral venous sinus thrombosis (CVST), but venous or arterial thrombosis at other locations can be present. The majority of those affected are younger adult females. Therefore, after a brief pause from April 13-23, 2021, the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) recommended caution in using this vaccine in females under 50 years. Based on the reported 28 cases of TTS after this vaccination (data till April 21, 2021) by CDC, 22 were females (78%), and 6 were male. None of those males had CVST but had thrombosis at other locations. We report the first case of a young male with TTS and CVST following Ad26.COV2.S vaccine presented with severe headache and diagnosed with acute right transverse and sigmoid cerebral venous sinus thrombosis, multiple right-sided pulmonary emboli, and right hepatic vein thrombosis. He was treated with parenteral anticoagulation with argatroban and intravenous immune globulin with the improvement of his symptoms. A heparin-induced thrombocytopenia with thrombosis (HITT) like syndrome caused by the genesis of a platelet-activating autoantibody against platelet factor 4 (PF4) triggered by adenoviral vector-based COVID-19 vaccinations is understood to be the underlying pathophysiology. TTS with CVST should be considered when patients present with headaches, stroke-like neurological symptoms, thrombocytopenia, and symptom onset 6-15 days after Ad26.COV2.S vaccination.

The era of lenalidomide maintenance therapy in multiple myeloma: settings for achieving best outcomes.

INTRODUCTION: For patients with multiple myeloma who are eligible for high-dose melphalan therapy and autologous stem cell transplant (ASCT), the strategy of maintenance with low-dose lenalidomide therapy has become the current standard of care. However, this strategy is not curative, and many unanswered questions remain regarding the optimization of lenalidomide-based maintenance therapy. AREAS COVERED: In this review, we evaluate the current data supporting the use of lenalidomide maintenance, either alone or in combination, following ASCT. We provide an overview of the management of lenalidomide-associated toxicities as well as address the unresolved topics of optimal treatment duration and use of minimal residual disease assessment. EXPERT OPINION: While single-agent lenalidomide maintenance is a current standard of care, a one-size-fits-all approach to maintenance therapy is not optimal. The rapidly evolving landscape of multiple myeloma therapy in conjunction with ongoing clinical trials should enable a future where an individualized approach based on disease characteristics, response to induction and ASCT (or even non-ASCT consolidation approaches such as CAR T-cell therapy or bispecific antibodies), as well as patient preferences will influence the use of lenalidomide maintenance.

Neoadjuvant Radiation with Concurrent 5-FU Resulting in Complete Pathologic Response in Stage IIIB Squamous Cell Carcinoma of the Urethra.

Squamous cell carcinoma (SCC) of the urethra is a rare malignancy, comprising less than 1% of all malignancies. The annual age-adjusted incidence of urethral SCC is 4.3 per million in men and 1.5 per million in women. Due to the rarity of the disease, there are a limited number of prospective randomized controlled trials to evaluate the optimal management of locally advanced urethral SCC. Here, we present the case of a 47-year-old man with stage IIIB urethral squamous cell cancer that showed complete clinical and pathologic response to neoadjuvant chemoradiation with only 5-flurouracil after incomplete response to traditional chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP).

Long-term Response to Vismodegib in a Patient with Gorlin-Goltz Syndrome: A Case Report and Review of Pathological Mechanisms Involved.

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome or Gorlin syndrome, is a rare multisystem disorder with an estimated prevalence of around 1 in 100,000 on average. Vismodegib, an oral smoothened (SMO) inhibitor that blocks the activation of the sonic hedgehog (SHH) pathway, is used in patients with NBCCS. We present an interesting case of a 38-year-old female with Gorlin-Goltz syndrome and her response to vismodegib therapy over two and a half years. She had an excellent initial response to vismodegib for a year during which all her skin basal cell carcinoma (BCC) lesions decreased in size considerably; her dentigerous cysts remained the same size. Though she continued therapy despite several side effects, this was only followed by tumor regrowth and the emergence of new BCC lesions in a more aggressive manner. We discussed the proposed mechanism of resistance to vismodegib (based on our case and literature review) along with its clinical implications. Our case highlights that vismodegib resistance might lead to progression of Gorlin syndrome to a more aggressive version, and points out the need to determine the optimal regimen (combining vismodegib with other agents) and optimal therapy duration (continuous treatment vs. discontinuation after best response) for treatment of NBCCS.

A Pedunculated Skin Lesion in a Case of Clear Cell Renal Carcinoma.

Clear cell type renal carcinoma accounts for about 80% of all renal cell carcinomas. We present a 39-year-old male with clear cell renal carcinoma of the right kidney, stage I: T1 b (5 cm) N0 M0, who developed cutaneous metastases in the right submandibular region 28 months after nephrectomy. Our case is unique as i) the patient with stage I cancer (at the time of nephrectomy) presented with an isolated cutaneous nodule in a location distant from the primary site; ii) cutaneous nodule developed while being treated with pazopanib for metastatic lesions in the lung and adrenal; and iii) nivolumab and ipilimumab combination therapy decreased the vascularity of the nodule though it did not halt the nodule growth. Physicians should be knowledgeable about this rare clinical entity and its varied presentation. Further studies are necessary to determine optimal treatment, as the current therapeutic agents for metastatic renal carcinoma might not be adequate for cutaneous metastasis.

Nivolumab-Induced, Late-Onset, Steroid-Sensitive, High-Grade Pneumonitis and Durable Tumor Suppression in Metastatic Renal Cell Carcinoma: A Case Report.

Nivolumab, an antiprogrammed death-1 checkpoint inhibitor, has been approved for use in unresectable/metastatic renal cell carcinoma (RCC). Nivolumab-induced pneumonitis, a rare, but often severe and potentially life-threatening immune-related adverse event, has been reported, typically, early during the treatment. Due to its low incidence, more studies are needed to better elucidate this condition and its possible effects on cancer progression. We now present a 57-year-old Hispanic male patient with metastatic RCC-clear cell type who, after his 34th cycle of nivolumab (16 months after being on nivolumab), developed a late-onset, immune-related adverse event (IRAE) including a grade 3 pneumonitis, which resolved completely, clinically, and on serial lung imaging with steroids and drug discontinuation. His cancer remained stable with no progression for 18 months despite discontinuation of nivolumab which showed tumor progression resistance. This case report is aimed at providing further information regarding the rare phenomena of a late-onset IRAE, in particular, a grade 3 nivolumab-induced pneumonitis which also responded rapidly to treatment, as well as at discussing this immunotherapy's durable tumor suppressive effect and a possible associated factor to this phenomenon.