scholarly journals Case Report: Good responsiveness of metastatic sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation to immune checkpoint inhibitor after radical surgery and adjuvant chemotherapy

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1458
Author(s):  
Hyung Ho Lee ◽  
Hye Ju Kang ◽  
Weon Seo Park ◽  
Wonyoung Choi ◽  
Ho Kyung Seo ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Radical Surgery ◽  
Checkpoint Inhibitor ◽  
Final Diagnosis ◽  
Histological Variant ◽  
Grade 3 ◽  
The Right

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation (SUCCD) in the ureter has a poor prognosis and is a rare histological variant of ureteral cancer. The majority of ureteral cancers are urothelial carcinomas. Clinical case: We present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor after radical surgery and failed adjuvant chemotherapy. The patient was a 68-year-old male with previous cure history of cT1 staged esophageal squamous cell carcinoma referred to the urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass. After ureteroscopic biopsy and intraureteral urine cytology, atypical pleomorphic cell nests and chondroid tissue consistent with sarcomatoid urothelial carcinoma were observed. The patient underwent a successful radical right nephroureterectomy with bladder cuffing. The final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma (heterologous component: chondrosarcoma > 95%) located at the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. On the postoperative one-month follow-up computed tomography scan, multiple enlarged lymph nodes and metastatic lung nodules were detected. The initiated adjuvant three cycles of gemcitabine-carboplatin therapy was marked by disease progression; thus, second-line therapy with atezolizumab was used for treatment. After five cycles of atezolizumab, the tumors showed a partial response without any grade 3 complications. Conclusion: The recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after unsuccessful therapy with radical surgery and first line chemotherapy despite the unfavorable outcome of the pathology.

scholarly journals 630 Oncologists' perspectives on evolution of first-line immune checkpoint inhibitor maintenance therapy in management of advanced urothelial carcinoma in the US

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A660-A660
Author(s):  
Petros Grivas ◽  
Phani Veeranki ◽  
Kevin Chiu ◽  
Vivek Pawar ◽  
Jane Chang ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Control ◽  
Urothelial Carcinoma ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Treatment Patterns ◽  
First Line ◽  
Platinum Based Chemotherapy

BackgroundAvelumab, a PD-L1 immune checkpoint inhibitor (ICI), was recently approved as first-line (1L) maintenance therapy for locally advanced/unresectable or metastatic urothelial carcinoma (aUC) after disease control with platinum-based chemotherapy.1 Given the evolving treatment landscape, the study aim was to gain real-world insights into clinical decision-making among oncologists for patients with aUC.MethodsIn March 2021, a cross-sectional web-based survey was administered to a sample of US oncologists treating patients with aUC. Oncologists' demographics, practice characteristics, and treatment patterns were obtained; descriptive statistics were used.ResultsThe study included 151 medical oncologists, who reported that 54% and 31% of their patients, on average, would be classified as cisplatin or carboplatin eligible for their 1L treatment, respectively. Approximately 78% of oncologists (n=118) considered using ICI maintenance in ≥40% of their patients following disease control with platinum chemotherapy and were categorized as the “high-consideration” group, for further exploratory analysis; the rest (22%) were in the low-consideration group (See table 1). Approximately, 31% and 27% of oncologists in the high- and low-consideration groups reported administering ICI maintenance with a 2–3-week gap after chemotherapy, while 45% and 46% reported administering it with a 4–6-week gap after chemotherapy, respectively.ConclusionsSurveyed oncologists reported that 85% of patients with aUC in US may be eligible for platinum-based chemotherapy. Further, 78% of the surveyed oncologists would consider 1L ICI maintenance therapy after disease control with platinum-based chemotherapy for over 40% of their patients. Future studies are warranted to evaluate real-world treatment patterns, barriers, and utilization of ICI maintenance therapy as the new 1L standard of care.AcknowledgementsThe authors would like to acknowledge all physicians at who participated and completed the survey for the study.ReferencePowles T, et al. N Engl J Med 2020;383(13):1218–1230.Ethics ApprovalThe study was reviewed and determined to be exempt by Advarra IRB.ConsentAll survey participated signed a consent form.Abstract 630 Table 1Oncologists characteristics and considerations for 1L ICI maintenance therapy

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

scholarly journals Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianyang Fu ◽  
Wang-Zhong Li ◽  
Nicole A. McGrath ◽  
Chunwei Walter Lai ◽  
Gagandeep Brar ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Meta Analysis ◽  
High Grade ◽  
Liver Cancers ◽  
Grade 3

BackgroundOverall risks of hepatotoxicity with immune checkpoint inhibitors (ICIs) have yet to be compared in primary liver cancers to other solid tumors.MethodsWe reviewed data from the PubMed, Embase, and Scopus databases, and assessed the risk of hepatotoxicity associated with ICIs.ResultsA total of 117 trials were eligible for the meta‐analysis, including 7 trials with primary liver cancers. The most common hepatotoxicity was ALT elevation (incidence of all grade 5.29%, 95% CI 4.52-6.20) and AST elevation (incidence of all grade 5.88%, 95% CI 4.96-6.97). The incidence of all grade ALT and AST elevation was 6.01% and 6.84% for anti-PD‐1 (95% CI 5.04-7.18/5.69-8.25) and 3.60% and 3.72% for anti-PD-L1 (95% CI 2.72-4.76/2.82-4.94; p< 0.001/p<0.001). The incidence of ≥ grade 3 ALT and AST elevation was 1.54% and 1.48% for anti-PD‐1 (95% CI 1.19-1.58/1.07-2.04) and 1.03% and 1.08% for anti-PD-L1 (95% CI 0.71-1.51/0.80-1.45; p= 0.002/p<0.001). The incidence of all grade ALT and AST elevation was 13.3% and 14.2% in primary liver cancers (95% CI 11.1-16.0 and 9.93-20.36) vs. 4.92% and 5.38% in other solid tumors (95% CI 4.21-5.76 and 4.52-5.76 in other solid tumors; p <0.001/p<0.001).ConclusionOur study indicates that anti-PD-1 is associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to anti-PD-L1, and primary liver cancers are associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to other solid tumors.

scholarly journals Phase Ib/II trial of ibrutinib and nivolumab in patients with advanced refractory renal cell carcinoma1

Kidney Cancer ◽  
2021 ◽  
pp. 1-7
Author(s):  
Mamta Parikh ◽  
Matthew E. Tenold ◽  
Lihong Qi ◽  
Frances Lara ◽  
Daniel Robles ◽  
...  
Keyword(s):  
Dose Level ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Once Daily ◽  
Checkpoint Inhibitor Therapy ◽  
Level 1 ◽  
Grade 3 ◽  
Expansion Cohort

Background: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. Methods: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). Results: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). Conclusions: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.

Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14525-e14525
Author(s):  
Abdul Miah ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
Madison Grogan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Grade 3

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

scholarly journals Diagnostic utility of CT for suspected immune checkpoint inhibitor enterocolitis

2020 ◽  
Vol 8 (2) ◽  
pp. e001329
Author(s):  
Sienna M Durbin ◽  
Meghan J Mooradian ◽  
Florian Johannes Fintelmann ◽  
Leyre Zubiri ◽  
Donald F Chute ◽  
...  
Keyword(s):  
Ct Scan ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Primary Objective ◽  
Institutional Review ◽  
Grade 3 ◽  
Sensitivity Specificity ◽  
Tumor Types

Background and aimsImmune checkpoint inhibitor (ICI) enterocolitis is a common immune-related adverse event and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, but CT scan is a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of ICI enterocolitis.MethodsWith institutional review board approval, we conducted a retrospective cohort study of patients who received ICI therapy between 2015 and 2019 across a healthcare system. Patients were included if they underwent both abdominal CT and endoscopy with biopsy within 3 days. The radiological and pathological diagnoses, as well as clinical characteristics, were extracted from the electronic medical record. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT for diagnosing ICI enterocolitis when compared with tissue diagnosis.ResultsOf the 4474 patients screened, 138 met inclusion criteria. Most common tumor types were melanoma (37%) and lung cancer (19%). Seventy-four per cent were treated with antiprogrammed cell death (PD-1)/PD-L1 therapy. Thirty-nine per cent had signs of enterocolitis on CT scan and 58% had biopsy-proven ICI enterocolitis. Sensitivity and specificity of CT were 50% and 74%, respectively. PPV was 73% and NPV was 52%. Of those with confirmed ICI enterocolitis, 70% had grade 3 or higher symptoms, 91% received steroids and 40% received infliximab.ConclusionThe performance of CT scan for diagnosis of ICI enterocolitis is moderate to poor and does not replace endoscopy with biopsy.

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