Multiple immune-related adverse events and anti-tumor efficacy: real-world data on various solid tumors

Abstract Background Immune checkpoint inhibitors have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in the real-world practice. Methods We conducted a retrospective study on patients with recurrent or metastatic non-small cell lung cancer, melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model. Results Among 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. OS in patients with multiple irAEs was significantly longer than that in patients with single irAE (42.3 months vs. 18.8 months; hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25–0.93; P = 0.03). Moreover, OS from the development of a second irAE in those with multiple irAEs was longer than that from the development of the first irAE in patients with single irAEs (median OS, 26.9 months vs. 17.7 months, respectively; HR, 0.59; 95% CI, 0.30–1.14; P = 0.11). Conclusions Our single-center retrospective study revealed a remarkable tendency associating the development of multiple irAEs with favorable prognoses.

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Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.110 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 110-110 ◽

Cited By ~ 5

Author(s):

Sean Khozin ◽

Mark S. Walker ◽

Monika Jun ◽

Li Chen ◽

Edward Stepanski ◽

...

Keyword(s):

Autoimmune Disease ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

The Impact

110 Background: Anecdotal and early evidence suggest ICIs are being used in patients with advanced malignancies and history of AD, despite such patients being typically excluded from traditional clinical trials. We compared the outcomes of patients with or without AD, all of whom had ICI treatment for aNSCLC. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in ASCO’s CancerLinQ. Patients with Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 visits from Jan 2011 to Nov 2018 were included. AD status prior to ICI treatment was identified using ICD-9/ICD-10 codes or AD medications (including steroids). Symphony claims data were linked via tokenization to build cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS) and overall survival (OS) were compared across the two cohorts using the log-rank test. Cox Proportional Hazards Model was used to adjust for covariates. Adverse events (AEs) were compared using Chi-Square and Fisher’s Exact Test. Active AD was defined as evidence of autoimmune disease in the year prior to starting ICIs. Results: Among 2425 patients with aNSCLC treated with ICIs, AD was present in 22% (N=538). Median OS in all patients was 12.4 months (95% CI 11.3-13.5). TTD, TTNT, rwPFS and OS did not differ between the two cohorts (Table). There was no association between AD status and outcomes. There was no increased incidence of AEs in the AD group; however a sub-analysis among patients with active AD showed higher rates of select AEs including endocrine, GI and blood disorders. Conclusions: This analysis demonstrates that patients with evidence of AD prior to receiving ICI have similar outcomes compared to patients with no evidence of AD. Further research is needed to better understand the impact of active AD on the risk of AEs and patient outcomes. [Table: see text]

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Effects of Serum Albumin Levels on Antithrombin Supplementation Outcomes Among Patients With Sepsis-Associated Coagulopathy: A Retrospective Study

Clinical Medicine Insights: Blood Disorders ◽

10.1177/1179545x19858361 ◽

2019 ◽

Vol 12 ◽

pp. 1179545X1985836

Author(s):

Masatomo Ebina ◽

Kazunori Fujino ◽

Akira Inoue ◽

Koichi Ariyoshi ◽

Yutaka Eguchi

Keyword(s):

Retrospective Study ◽

Serum Albumin ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Term Survival ◽

Hazards Model ◽

The Relationship

Background:Severe sepsis is commonly associated with mortality among critically ill patients and is known to cause coagulopathy. While antithrombin is an anticoagulant used in this setting, serum albumin levels are known to influence serum antithrombin levels. Therefore, this study aimed to evaluate the outcomes of antithrombin supplementation in patients with sepsis-associated coagulopathy, as well as the relationship between serum albumin levels and the effects of antithrombin supplementation.Methods:This retrospective study evaluated patients who were >18 years of age and had been admitted to either of two intensive care units for sepsis-associated coagulopathy. The groups that did and did not receive antithrombin supplementation were compared for outcomes up to 1 year after admission. Subgroup analyses were performed for patients with serum albumin levels of <2.5 g/dL or ⩾2.5 g/dL.Results:Fifty-one patients received antithrombin supplementation and 163 patients did not. The Cox proportional hazards model revealed that antithrombin supplementation was independently associated with 28-day survival (hazard ratio [HR]: 0.374, P = 0.025) but not with 1 year survival (HR: 0.915, P = 0.752). In addition, among patients with serum albumin levels of <2.5 g/dL, antithrombin supplementation was associated with a significantly lower 28-day mortality rate (9.4% vs 36.8%, P = .009).Conclusion:Antithrombin supplementation may improve short-term survival, but not long-term survival, among patients with sepsis-associated coagulopathy.

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The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009635 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009635

Author(s):

Selma Regina Penha Silva Cerqueira ◽

Patrícia Duarte Deps ◽

Débora Vilela Cunha ◽

Natanael Victor Furtunato Bezerra ◽

Daniel Holanda Barroso ◽

...

Keyword(s):

Cohort Study ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Significant Risk ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Protective Effects ◽

Bcg Vaccination ◽

Patients At Risk

Background Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. Methodology/Principal findings We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93–13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04–4.06) were significant risk factors for COVID-19. Conclusions/Significance Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

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Overall survival (OS) with docetaxel (D) vs novel hormonal therapy (NHT) with abiraterone (A) or enzalutamide (E) after a prior NHT in patients (Pts) with metastatic prostate cancer (mPC): Results from a real-world dataset.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5537 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5537-5537 ◽

Cited By ~ 1

Author(s):

Umang Swami ◽

Jennifer Anne Sinnott ◽

Ben Haaland ◽

Benjamin Louis Maughan ◽

Nityam Rathi ◽

...

Keyword(s):

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Single Agent ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Metastatic Setting ◽

Subgroup Analyses ◽

Icd Codes

5537 Background: NHT (A and E) are approved first-line (1L) treatment (Rx) for mPC. After progression on NHT, Rx include either alternate NHT or D. However, OS from a randomized trial comparing NHT vs D after progression on 1L NHT has not been reported. Methods: Pts data were extracted from the Flatiron Health EHR-derived de-identified database. Inclusion: diagnosis of mPC; 1L Rx with single agent A or E only, single-agent Rx with alternate NHT (E or A) or D in second line (2L). Exclusion: > 180 days between date of diagnosis of mPC and date of next visit to ensure Pts were actively engaged in care at data-providing site; Rx with NHT in non-metastatic setting, any prior exposure to D. OS was compared using Cox proportional hazards model stratified by Rx propensity score. Each Pts’ probability of receiving D (rather than NHT) was modeled via a random forest based on Pts and disease characteristics which may drive treatment selection. These included pre-2L Rx ECOG scores, PSA, LDH, ALPH, Hb, age, ICD codes for liver metastasis, diabetes, neuropathy, and heart failure; insurance payer, year of start of 2L Rx, time on 1 L NHT, Gleason score, PSA at the original diagnosis of mPC. Subgroup analyses included 1L Rx duration < 12 mos. Results: 1165 Pts between 2/5/2013 to 9/27/2019 were eligible. Median follow up 8 mos (range 0.1-64.5). Median OS after 1L A was higher with E as compared to D (15.7 vs. 9.4 mos). Median OS after 1L E was higher with A as compared to D (13.3 vs. 9.7 mos) (table). Propensity distributions were overlapping among Rx arms and showed only modest imbalance. In 2L, D had a worse adjusted hazard ratio of 1.29 and 1.35 as compared to E and A respectively (p < 0.05). Similar results were seen with 1L Rx duration of < 12 mos (p < 0.05). Conclusions: These hypothesis-generating data provide real-world OS estimates with 2L D & NHT in mPC. In propensity-stratified analyses, mPC Pts who progressed on NHT had a worse OS with 2L D as compared to alternate NHT. Results were consistent in unadjusted analysis & subgroup analyses of 1L Rx < 12 mos. Results are subject to residual confounding and missingness. After prospective validation these data may aid in Rx sequencing, Pts counselling, and design of future clinical trials in this setting. [Table: see text]

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Does concurrent COX inhibition and immune checkpoint blockade improve clinical outcome in patients with metastatic renal cell carcinoma?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16558 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16558-e16558

Author(s):

Yumeng Zhang ◽

Jacob J. Adashek ◽

Premsai Kumar ◽

William Paul Skelton ◽

Jiannong Li ◽

...

Keyword(s):

Lung Cancer ◽

Immune Checkpoint ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Checkpoint Inhibitors ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Center ◽

Test Time ◽

Concurrent Use

e16558 Background: Cyclooxygenase (COX) inhibition is postulated to restore the immune environment and synergizes with immune checkpoint inhibitors (ICI). The concurrent use of COX inhibitors (COXi) and ICI was associated with longer disease control in metastatic melanoma and non-small cell lung cancer. However, its role in mRCC remains unclear. Methods: We retrospectively reviewed 194 patients with mRCC treated with ICI (PD-(L)1 inhibitors +/- CTLA-4 inhibitors or TKIs) at Moffitt Cancer Center between 6/2014-7/2019. Concurrent use of COXi (aspirin [ASA] or NSAIDs) was defined as at least 3 weeks of COXi use during the first ICI course. Clinical characteristics of both arms were compared using Chi-squared or Kruskal-Wallis Rank Sum test. Time to progression (TTP) and Overall survival (OS) were compared using Kaplan Meier’s estimates. Univariate and multivariate Cox proportional hazards model was performed to evaluate the association between clinical factors, TTP, and OS. Results: Of 194 patients, 126 patients (64.9%) took COXi. Median age was 59.7 years and 80.4% were male. COXi arm had fewer patients with < 1 year from diagnosis to systemic treatment (45.9% vs 69.5%, p = 0.006) and more advanced age (median: 66 years vs 60 years, p = 0.01). IDMC risk group, number of prior therapies, neutrophil to lymphocytes ratio were similar between both arms. Median TTP was 8 months (m) for COXi arm and 12m for ICI only (HR 1.38; 95% CI [0.98, 1.94]). Median OS was 27m for COXi arm and 33m for ICI only (HR 1.05, 95% CI [0.69, 1.59]). Early mortality rate (within 3m of ICI treatments) were similar between both arms. Conclusions: In contrast to melanoma and lung cancer, concurrent use of COXi and ICI did not improve TTP and OS in patients with mRCC. The dual blockade showed a trend for shorter TTP. Further validation studies with larger cohorts are needed to confirm this finding.[Table: see text]

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Needlestick injuries at a tertiary teaching hospital in Singapore

Epidemiology and Infection ◽

10.1017/s0950268816000893 ◽

2016 ◽

Vol 144 (12) ◽

pp. 2546-2551 ◽

Cited By ~ 3

Author(s):

M. SENG ◽

G. K. J. SNG ◽

X. ZHAO ◽

I. VENKATACHALAM ◽

S. SALMON ◽

...

Keyword(s):

Incidence Rate ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Injury Rate ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

University Hospital ◽

Needlestick Injuries ◽

Tertiary Teaching ◽

Prevention Programmes

SUMMARYThis study investigated the incidence and risk to staff groups for sustaining needlestick injuries (NSIs) in the National University Hospital (NUH), Singapore. A retrospective cohort review of incident NSI cases was undertaken to determine the injury rate, causation, and epidemiological profile of such injuries. Analysis of the risk of sustaining recurrent NSI by occupation and location was done using the Cox proportional hazards model. There were 244 NSI cases in 5957 employees in NUH in 2014, giving an incidence rate of 4·1/100 healthcare workers (HCWs) per year. The incidence rate was highest for doctors at 21·3, and 2·7 for nurses; 40·6% of injuries occurred in wards, and 32·8% in operating theatres. There were 27 cases of repeated NSI cases. The estimated cost due to NSIs in NUH ranged from US$ 109 800 to US$ 563 152 in 2014. We conclude that creating a workplace environment where top priority is given to prevention of NSIs in HCWs, is essential to address the high incidence of reported NSIs. The data collected will be of value to inform the design of prevention programmes to reduce further the risk of NSIs in HCWs.

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Survival of Preterm Singleton Deliveries: A Population-Based Retrospective Study

Advances in Epidemiology ◽

10.1155/2015/858274 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Boubakari Ibrahimou ◽

Sireesha Kodali ◽

Hamisu Salihu

Keyword(s):

Retrospective Study ◽

Preterm Birth ◽

Caesarean Section ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Postneonatal Mortality ◽

Increased Risk

Aim. To identify sociodemographic and medical characteristics associated with preterm birth survival. Methods. A retrospective study of singleton births was performed using Missouri linked data for the years 1978 to 2005. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards model. Results. High rates of infant, neonatal, and postneonatal mortality were observed among preterm as compared to term births. White are at low risk for postneonatal (HR = 0.77, CI: 0.65, 0.90) and infant mortality (HR = 0.90, CI: 0.81, 0.99) compared to blacks. We observed increased risks of all mortality types for preterm deliveries by caesarean section (neonatal HR = 1.53, CI: 1.40, 1.68; postneonatal HR = 1.39, CI: 1.22, 1.58; infant HR = 1.37, CI: 1.27, 1.48). As compared to nonsmokers, preterm singletons born to smoking mothers are 69% more likely to experience postneonatal mortality and have a 17% increased risk for infant death. Conclusions. Caesarean section is associated with increased risk of all types of mortality. Racial disparity is still a concern. Further research is required to identify the detailed differences in structure and procedures that result in the disadvantage associated with preterm birth especially with respect to caesarean section and race.

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Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia

Annals of Hematology ◽

10.1007/s00277-019-03830-8 ◽

2019 ◽

Vol 98 (12) ◽

pp. 2749-2760 ◽

Cited By ~ 3

Author(s):

Gilles Salles ◽

Emmanuel Bachy ◽

Lukas Smolej ◽

Martin Simkovic ◽

Lucile Baseggio ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Real World ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Relative Effectiveness ◽

Single Agent ◽

Cox Proportional Hazards ◽

Lymphocytic Leukemia ◽

Cox Proportional Hazards Model ◽

Treatment Naïve

AbstractAfter analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab–containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14–0.37; p < 0.0001) and 0.40 (0.22–0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16–0.27; p < 0.0001) and 0.29 (0.21–0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22–0.63; p = 0.0003) for PFS and 0.53 (0.27–1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

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Comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in metastatic pancreatic cancer: A nationwide chart review in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.376 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 376-376

Author(s):

Sunnie S. Kim ◽

James Signorovitch ◽

Hongbo Yang ◽

Oscar Patterson-Lomba ◽

Cheryl Xiang ◽

...

Keyword(s):

Real World ◽

Medical Records ◽

Proportional Hazards Model ◽

Specific Treatment ◽

The United States ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Real World Data ◽

Significant Difference ◽

Treatment Sequences

376 Background: nab-Paclitaxel plus gemcitabine ( nab-P+G) and FOLFIRINOX (FFX) are among the most common first-line (1L) therapies for metastatic adenocarcinoma of the pancreas (mPC), yet there is no head-to-head trial comparing their efficacy and real-world data is limited. As new second-line (2L) therapies become available, it is important to understand the real-world effectiveness associated with different treatment sequences. Methods: This retrospective cohort study compared the efficacy and safety of 1L nab-P+G vs. FFX, overall and under specific treatment sequences. Medical records were reviewed by 215 physicians across the US who provided information for mPC patients who initiated 1L with nab-P+G or FFX between 04/01/2015-12/31/2015. The outcomes of interest were overall survival (OS) and tolerability. OS was evaluated using Kaplan-Meier curves, and compared between cohorts using Cox proportional hazards model adjusting for baseline characteristics. Results: Medical records were reviewed for 654 patients receiving nab-P+G (n = 337) or FFX (n = 317) as 1L therapy for mPC. Patients in the nab-P+G cohort were older, less likely to have ECOG ≤ 1 and had more comorbidities than patients in the FFX cohort. There was no statistically significant difference in OS (adjusted HR = 0.99, p = 0.96), with median OS (mOS) being 12.1 and 13.8 months for nab-P+G and FFX, respectively. Among the subgroup of patients with ECOG ≤ 1, mOS was 14.1 and 13.7 months, respectively (adjusted HR = 1.00, p = 0.99). Among patients with 1L nab-P+G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of 16.3 and 16.6 months, respectively (HR = 1.04, p = 0.76). Among commonly observed adverse events (AEs) (≥ 5% of patients in both cohorts), the rates of diarrhea, fatigue, mucositis, nausea and vomiting were higher in the FFX than nab-P+G cohort (all p < 0.05). Conclusions: In a nationwide sample of mPC patients, real-world survival outcomes were similar between patients receiving 1L nab-P+G or FFX. both overall and among patients who went on to receive active 2L treatments. In addition, nab-P+G was associated with significantly lower rates of common AEs compared with FFX.

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Multi-institutional analysis of outcomes in patients with dedifferentiated chondrosarcoma (DDCS).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11028 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11028-11028

Author(s):

Nam Bui ◽

Hilary Dietz ◽

Angela C. Hirbe ◽

Kristen N. Ganjoo ◽

Brian Andrew Van Tine ◽

...

Keyword(s):

Poor Prognosis ◽

Kinase Inhibitors ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Checkpoint Inhibitors ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Nccn Guidelines ◽

Neo Adjuvant Chemotherapy

11028 Background: DDCS is a rare bone tumor with a poor prognosis. While no standard therapy exists, NCCN guidelines recommend osteosarcoma regimens (ORs). Methods: We performed a retrospective review (January 1, 2007-June 1, 2018) at three sarcoma centers and identified 46 patients (pts) with DDCS to evaluate treatments and outcomes. Results: Median age was 62.5 years (23-83); 61% were male. Median tumor size was 10.5cm (2-34). Most pts had localized disease at diagnosis (dx) (80%), extremity primary (76%), and did not receive neo/adjuvant chemotherapy (70%) or radiotherapy (69%). Local and distant recurrences were frequent (35% and 57%, respectively) and rapid (6.6 months (m) and 5.4 m, respectively). Twenty-eight pts received chemotherapy, 9 neo/adjuvant and 19 for metastasis (met) (Table). Response rate to first line ORs was poor (53% progressed). Notably, 11% had a partial response (D/I). Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) led to stable disease. Median overall survival was 22.8 m and 7.2 m; 5-year survival rates were 30% and 0% in localized and metastatic disease, respectively. Median follow-up was 12.5 m (1.4-120). A multivariate cox proportional hazards model (age, sex, location, met at dx) identified met at dx as the only risk factor for worse prognosis (HR 2.8, p=0.026). Conclusions: DDCS is an aggressive malignancy with a poor prognosis. Despite guidelines to treat with ORs, the benefit is unclear, illustrating the need for randomized trials comparing standard regimens to novel agents. [Table: see text]

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