Objectives: Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dualagent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment.Materials and Methods: A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.Results: Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab.Conclusions: This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on singleagent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.
Objectives: Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs. Materials and Methods: We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival. Results: We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival. Conclusions: We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.
569 Background: CPIs targeting PD-1/PD-L1 and CTLA-4 have transformed management of GU cancers. These agents are associated with a unique type of immune-mediated toxicities that may affect any organ, which may be severe or life-threatening. Development of irAEs may in part depend on type of CPI used, type of solid tumor, and individual patient factors including presence of subclinical inflammatory states. However, distinct biomarkers predictive of irAE development are poorly defined. This study aimed to examine possible associations between tumor mutation burden (TMB) and PD-L1 expression with occurrence of irAEs. Methods: A retrospective chart review was performed of all patients with urothelial carcinoma (UC) and renal cell carcinoma (RCC), who received therapy with CPIs from 1/2019 to 9/2022 at our institution and developed associated irAEs. Severe irAEs were defined as those necessitating initiation of immunosuppressive therapies or other supportive therapies. TMB and PDL-1 expression patterns were analyzed, if available. Given lack of standardized cutoffs for PD-L1 positivity across different GU cancer types, tumors were considered positive if a combined positive score of greater than 10 was present in UC or a total positive score of greater than 1% was present in RCC. Results: A total of 60 patients were included in this analysis - 33 with UC and 27 with RCC. Severe irAEs occurred in 19 patients with UC and 25 patients with RCC. Median TMB was 8.7 in patients with UC, while it was 2.5 in patients with RCC. PD-L1 positivity was seen in 39.3% (13/33) of UC patients and 40.7% (11/27) of RCC patients. In the UC cohort, 57.8% (11/19) had severe irAEs and TMB less than 10, while 36.8% (7/19) had severe irAEs and TMB greater than 10. Further, 47.3% (9/19) of UC patients had severe irAEs and positive PD-L1, while 42.1% (8/19) had severe irAEs and negative PD-L1. In the RCC cohort, 88% (22/25) had severe irAEs and TMB less than 10, while 8% (2/25) had severe irAEs and TMB greater than 10. Additionally, 40% (10/25) RCC patients had severe irAEs and positive PD-L1, while 56% (14/25) had severe irAEs and negative PD-L1. The incidence of TERT promoter mutations and TMB is noted in the table. Conclusions: Identification of predictive biomarkers of irAEs from CPIs is a major area of need in GU malignancies. Definitive conclusions from this dataset are limited by its small sample size. Interestingly, there appear to be differences in baseline expression of traditional immune biomarkers between UC and RCC, with lower prevalence of TMB greater than 10 and positive PD-L1 noted in the RCC cohort. As such, their utility when making treatment decisions in clinical practice may be of limited value. [Table: see text]
79 Background: Recent approvals in management of high-volume mCSPC offer major improvements in patient outcomes. Triplet therapy combining androgen deprivation therapy (ADT) with docetaxel (D) and novel hormonal therapy (NHT) is the new standard of care in this patient population. Patients ineligible for triplet therapy should receive doublet therapy with ADT plus D or NHT based on category 1 evidence. Multiple retrospective datasets examining the “real-world” mCSPC treatment landscape note significant underutilization of therapies beyond ADT and discordance with treatment guidelines. Methods: A 15-question survey to assess management patterns was electronically distributed to various mCSPC providers in California and Washington. Results: A total of 40 responses were received, with 62.5% identifying as medical oncologists (MO), 20.0% as urologists, 5.0% as radiation oncologists, and 12.5% as advanced practitioners/other. Out of physician responders, 48.6% were academic and 51.4% were community-based. When treating newly diagnosed fit mCSPC patients, 20.0% would prescribe triplet therapy, 42.5% ADT/NHT, 5.0% ADT/D, 5.0% ADT/bicalutamide, 0% ADT alone, 10.0% other therapies, and 17.5% would refer out for therapies beyond ADT. When comparing academic versus community oncologists, 66.7% versus 0% would prescribe triplet therapy, while 22.2% versus 68.8% would prescribe ADT/NHT. Some perceived barriers to following mCSPC treatment guidelines included difficulty keeping up with rapidly evolving data/too many treatment options in 27.5%, insurance coverage concerns in 22.5%, difficulty obtaining early referrals for these therapies in 12.5%, patient factors in 10.0%, and toxicity concerns in 2.5%. When making referrals to MO, 37.5% of non-MO responders would do so at development of mCSPC and 6.3% at mCRPC. Conversely, 24.2% of MO perceived receiving referrals at development of mCSPC and 33.3% at mCRPC. Patterns of ordering genomic testing are listed, with biggest perceived barriers being cost, inadequate access to sequencing platforms and genetic counselors, lack of confidence in counseling about results, and patient refusal. Upon progression from mCSPC to mCRPC, ordering of repeat tumor biopsies would occur “sometimes” by 40.0% of providers, “rarely” by 20.0%, and “never” by 20.0%. Conclusions: Multiple provider disparities when managing mCSPC patients still exist. Our survey demonstrated higher compliance with treatment guidelines than in previous retrospective datasets, possibly due to higher proportion of academic providers. Increased provider awareness of genomic testing recommendations is also needed. [Table: see text]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.