Explore the vast range of titles available.

The primary endpoint was progression-free survival, with the secondary endpoints of overall response rate, time to deterioration of quality of life, disease control rate, duration of response, safety, and overall survival; crossover was allowed following confirmed progression by central review. Time to deterioration in quality of life showed no significant difference between groups. [...]of the primary analysis, the median overall survival had not yet been reached for either group, but no difference in overall survival was observed between the treatment groups at follow-up.

Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC ( NCT02826486 ). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N  = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8 + effector T cell tumor infiltration, decreased myeloid-derived suppressor cells (MDSCs) and further decreased circulating regulatory T cells. In cohort 2, 22 patients received BL-8040 and pembrolizumab with chemotherapy, with an ORR, DCR and median duration of response of 32%, 77% and 7.8 months, respectively. These data suggest that combined CXCR4 and PD-1 blockade may expand the benefit of chemotherapy in PDAC and warrants confirmation in subsequent randomized trials. Results from the phase IIa COMBAT trial combining CXCR4 and PD-1 inhibition in patients with metastatic cancer show encouraging clinical responses in association with enhanced antitumor immune activation.

Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These render a cancer dependent on that specific mutation's biochemical pathway for its growth and survival. With the development of tyrosine kinase inhibitors and antibodies against specific driver mutations, the landscape of lung cancer treatment has changed from treatment based on histologic subtype to treatment based on molecularly defined subtypes. In this article, we review the current molecular-targeted therapies in lung cancer. We review landmark trials that have led to approval of molecular-targeted therapies against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. We also explore less common mutations/molecular abnormalities and review data on the use of targeted therapies against them. Finally, we offer a treatment algorithm for patients with metastatic NSCLC that harbors actionable mutations. Patients with advanced NSCLC should undergo mutational testing to evaluate for actionable mutations. If such a mutation is discovered, targeted therapy should be considered for first-line treatment.

Objectives DIPNECH is a rare pre-neoplastic condition that often presents with a variety of non-specific pulmonary symptoms and sometimes seen in conjunction with pulmonary carcinoid tumors. There are very limited data on use of somatostatin analogs in patients with DIPNECH. We review the long-term outcomes of somatostatin analog therapy with regard to symptom control in patients with DIPNECH. Materials/Methods Retrospective study out of our extensive registry of over 2000 neuroendocrine tumors identifies 184 pulmonary neuroendocrine tumors. Out of this, there were five histopathologically confirmed cases of DIPNECH. Appropriate institutional review board permission was taken for this analysis. Results All 5 patients were females, with a mean age at diagnosis was 65.5 years. Follow-up period includes 1–5 years. Cough was the presenting complaint in all five patients described as mostly dry, except for one patient who had productive early morning cough. Other symptoms seen in one of our patients included wheezing, flushing, and fluctuating blood pressure. No one reported weight loss, hemoptysis, and shortness of breath. One of our patients had a benign thyroid nodule and two patients had previous history of breast cancer. All five of our patients were histopathologically diagnosed by lung biopsy. 4 out of 5 patients were started on a somatostatin analog. All four patients reported drastic improvement in cough. One patient reported mild abdominal discomfort and diarrhea as side effects but remained on treatment. Conclusions From our single institution review of neuroendocrine pulmonary tumor cases, we found only five cases of DIPNECH, which reaffirms rare nature of the pathology. It primarily affects females over 60 years with dry cough as the most common presenting symptom. Most of our patients responded to treatment with a somatostatin analog and had significant improvement in their presenting symptoms. Somatostatin analogs were well tolerated resulting in significant resolution of presenting symptoms in most of our patients. Further research is needed; however, a trial of somatostatin analogs should be considered in the treatment of patients with DIPNECH with responders being treated long term.

[sup.177]Lu-DOTATATE has changed the treatment landscape for patients with gastroenteropancreatic neuroendocrine tumors. As with all therapies, side effects are inevitable. For patients with a high burden of disease, treatment with [sup.177]Lu-DOTATATE can cause a tumor flare reaction, causing significant pain or other complications. There have been some reports on the use of corticosteroids to prevent this adverse effect. We aimed to see if we could achieve success at our institution when using corticosteroids to prevent a tumor flare reaction. We identified forty-six patients who receive corticosteroids in this setting. Twenty-eight percent of patients still had a tumor flare reaction with corticosteroid prophylaxis, and this statistic is similar to previously reported numbers. Twenty-eight percent of patients also experienced adverse effects from the corticosteroids used in this setting. Further studies are needed to examine the risks versus the benefits of corticosteroid use, so as to prevent tumor flare reactions in patients treated with [sup.177]Lu-DOTATATE with a high disease burden. Background/Objectives: Since [sup.177]Lu-DOTATATE was approved for patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (NETs), tumor flare reactions including increased pain and small bowel obstruction (SBO) have been reported. Retrospective reviews report some success in using corticosteroids for treatment and prophylaxis of tumor flare reactions from [sup.177]Lu-DOTATATE. Given that corticosteroids are used in practice to help prevent tumor flare reactions based on limited evidence, we aimed to assess if this practice was efficacious in our patient population. Methods: In this retrospective and single-institution study, we identified adult patients with NETs who were treated with [sup.177]Lu-DOTATATE between 1 October 2019 and 31 December 2024; these patients received corticosteroids as prophylaxis for flare reactions due to high burden of disease, significant peritoneal or mesenteric disease, or disease involvement of critical structures as determined by the treating provider. Variables including demographics, diagnosis, treatment history, steroid dosing, and outcomes were collected within a RedCAP database. Results: Forty-six patients were identified as having received corticosteroid prophylaxis to prevent a tumor flare reaction due to [sup.177]Lu-DOTATATE. Patients had a median age of 66, and 50% were female. The primary disease site was the small intestine (72%) followed by the pancreas (9%). The majority of patients had World Health Organization (WHO) grade 1 (41%) or WHO grade 2 (35%) diseases. Most patients (83%) received corticosteroids prior to the initiation of [sup.177]Lu-DOTATATE, while 17% of patients received corticosteroids due to having a previous tumor flare after [sup.177]Lu-DOTATATE administration. Despite corticosteroid prophylaxis, 28% of patients still experienced a tumor flare event, with three patients experiencing multiple tumor flare events. Small bowel obstructions occurred in 7% of patients and increased abdominal pain in 22% of patients. Adverse events (AEs) due to corticosteroids occurred in 28% of patients. Conclusions: Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with [sup.177]Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with [sup.177]Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.

Background/Objectives: Since 177Lu-DOTATATE was approved for patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (NETs), tumor flare reactions including increased pain and small bowel obstruction (SBO) have been reported. Retrospective reviews report some success in using corticosteroids for treatment and prophylaxis of tumor flare reactions from 177Lu-DOTATATE. Given that corticosteroids are used in practice to help prevent tumor flare reactions based on limited evidence, we aimed to assess if this practice was efficacious in our patient population. Methods: In this retrospective and single-institution study, we identified adult patients with NETs who were treated with 177Lu-DOTATATE between 1 October 2019 and 31 December 2024; these patients received corticosteroids as prophylaxis for flare reactions due to high burden of disease, significant peritoneal or mesenteric disease, or disease involvement of critical structures as determined by the treating provider. Variables including demographics, diagnosis, treatment history, steroid dosing, and outcomes were collected within a RedCAP database. Results: Forty-six patients were identified as having received corticosteroid prophylaxis to prevent a tumor flare reaction due to 177Lu-DOTATATE. Patients had a median age of 66, and 50% were female. The primary disease site was the small intestine (72%) followed by the pancreas (9%). The majority of patients had World Health Organization (WHO) grade 1 (41%) or WHO grade 2 (35%) diseases. Most patients (83%) received corticosteroids prior to the initiation of 177Lu-DOTATATE, while 17% of patients received corticosteroids due to having a previous tumor flare after 177Lu-DOTATATE administration. Despite corticosteroid prophylaxis, 28% of patients still experienced a tumor flare event, with three patients experiencing multiple tumor flare events. Small bowel obstructions occurred in 7% of patients and increased abdominal pain in 22% of patients. Adverse events (AEs) due to corticosteroids occurred in 28% of patients. Conclusions: Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with 177Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.

Experiencing HIV and intersectional stigmas in healthcare settings may affect antiretroviral treatment (ART) adherence among people with HIV (PWH), given their need for frequent interactions with clinical settings and healthcare providers. Considering the importance of reducing stigmas to promote well-being and the need to elucidate how stigma influences health across various settings, we examined how experienced HIV stigma in Dominican Republic healthcare settings impacts ART adherence through internalized HIV stigma and whether race or sexual orientation stigma moderates this relationship. Participants were 471 PWH (aged 17–71) who were recruited from two HIV clinics in the Dominican Republic in 2021–2022. Results revealed a significant mediation effect (B=-0.10, SE = 0.05, CI [-0.234, − 0.014]) after adjusting for effect of age and time since HIV diagnosis, suggesting that experienced HIV stigma in healthcare settings was associated with more internalized HIV stigma (B = 0.39, SE = 0.11, p = .001), subsequently linked to lower ART adherence (B=-0.26, SE = 0.11, p = .016). The indirect effect was significant at low levels of race stigma (B=-0.16, SE = 0.09, CI [-0.369, − 0.001]) but not at high levels of race stigma (B=-0.06, SE = 0.05, CI [-0.175, 0.038]). This indirect effect was also significant at low levels of sexual orientation stigma (B=-0.19, SE = 0.10, CI [-0.401, − 0.023]) but not at high levels of sexual orientation stigma (B=-0.04, SE = 0.06, CI [-0.160, 0.074]). These findings suggest that addressing experienced HIV stigma in Dominican Republic healthcare settings, along with various dimensions of HIV-related stigma (e.g., internalized stigma) and intersecting stigmas (e.g., race, sexual orientation), is vital for improving health outcomes, such as optimal ART adherence.

Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. Methods A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. Results Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients ( N  = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3–20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0–11). Conclusions Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.

Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.

Background: Neuroendocrine carcinomas (NECs) are treated with a frontline platinum–etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity. Methods: We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy. Eligible patients received nal-IRI 70 mg/m2 and leucovorin 400 mg/m2, followed by 5-FU 2400 mg/m2 biweekly till disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Next-generation sequencing (NGS) was performed on blood/tissue samples at baseline and during treatment. Results: Eleven patients were enrolled, with nine evaluable for the primary endpoint. Seven were male, the median age was 66.7 years, and the median Ki-67 was 90%. We observed partial response in one patient, stable disease in six patients, and progressive disease in two patients. The median OS was 9.4 months (95% CI 2.9–29.3), and the median PFS was 4.4 months (95% CI 1.7–6.7). The most common adverse events were diarrhea (45%), nausea (45%), vomiting (45%), and fatigue (45%). The most common genetic mutations on NGS were TP53 (88.9%), CHEK2 (88.9%), and APC (33.3%). Patients with CHEK2 and APC mutation had longer PFS (p = 0.005 and p = 0.013, respectively). UGT1A1*28 polymorphism was not associated with OS, PFS, or toxicity. Conclusion: Nal-IRI with 5-FU/LV is a safe and effective treatment for refractory high-grade NECs of GEP or unknown origin. Future studies should explore novel combinations with Nal-IRI in high-grade NECs both in frontline and refractory settings.