Retrospective study to assess the efficacy and safety of checkpoint inhibitors in advanced urothelial carcinoma in real-world setting.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17043-e17043
Author(s):  
Elena Sevillano Fernandez ◽  
Javier Puente ◽  
Natalia Vidal ◽  
Alvaro Pinto ◽  
Lourdes Garcia Sanchez ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Urothelial Carcinoma ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Molecular Study ◽  
Collaborative Group ◽  
First Line ◽  
Advanced Urothelial Carcinoma

e17043 Background: Checkpoint Inhibitors (CPI) have become a new standard of treatment in advanced urothelial carcinoma. However, little is known regarding the outcome of patients in daily practice.We aimed to assess tumor response and toxicity of CPIs in a cohort of patients treated in “real world” conditions. In parallel, a comprehensive molecular study in tumor samples from these patients, is ongoing. Methods: We designed an observational retrospective study within the “Grupo Centro” collaborative group. Adult patients diagnosed of metastasic urothelial carcinoma (mUC) and treated with CPIs between 2011-2019 in any of the 20 centers of the group, were eligible. Results: Up to date 100 patients have been included (82% males) with a median age of 74 years (48 -96). In 82% patients primary was bladder cancer. Most common metastasic sites were bone (26%) and liver (16%).With a median follow up of 10,6 months(mo) median progression free survival (mPFS) was 6,6mo (1,4-95,4 range) and median Overall Survival (mOS) was 21.3mo (3,8-121,8). 38% of patients received CPIs in first line(L): atezolizumab:27, pembrolizumab: 10, nivolumab:1. The median number of cycles was 8,2. Up to 51% received platinum-based combinations in first line. 69% (69/100) pts received 2L treatment: 68% with CPIs, 27,5% with chemotherapy and 4% with FGFR inhibitors (as part of a clinical trial). 2L mPFS was 3,5 mo (1,9-25.9). 23% (23/100) patients received 3L, of them 26% (6/23) were treated with CPIs. 3L mPFS:8,3mo(0,4-43,8). As a whole, patients treated with CPI accross different lines, achieved complete response in 8% of the cases, partial response in 18% and stable disease in 15%. Up to 44% of cases presented progressive disease as best response and evaluation was not available in 15%. Most common G1-2 AEs related to immunotherapy were: asthenia:31%,pruritus:16% and anorexia: 9%.10% pts experienced G3-4 toxicity: asthenia G3: 4, diarrhea G3: 1, erythrodysesthesia G3:1, arthromyalgia G3: 1, cardiac arrest G4:1,pneumonitis G4:1,anemia G3:1. Conclusions: This study confirms the efficacy and security of CPIs in real world. Response rates and toxicity profile were comparable to those reported in clinical trials.

scholarly journals First-Line Chemotherapy Response Is a Predictive Factor for Immune Checkpoint Inhibitors Treatment in Advanced Urothelial Carcinoma, a Real World Retrospective Study

2021 ◽  
Author(s):  
Jian-Ri Li ◽  
Shian-Shiang Wang ◽  
Kevin Lu ◽  
Chuan-Shu Chen ◽  
Chen-Li Cheng ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
The Other ◽  
Chemotherapy Response ◽  
First Line ◽  
Advanced Urothelial Carcinoma ◽  
Line Chemotherapy

Abstract Background: Immune checkpoint inhibitors (ICIs) have become important tools for the treatment of advanced urothelial carcinoma (aUC). However, the clinical strategy using ICIs and chemotherapy is still controversy. The aim of this study was to evaluate the association of clinical parameters in aUC patients with ICIs treatment.Methods: We retrospectively analyzed aUC patients who received atezolizumab and pembrolizumab between January 2015 and October 2020. The associations between baseline demographics and clinical outcomes were evaluated.Results: Of the 74 included patients, the median age was 67 years. Among them, 53 patients received atezolizumab and the other 21 received pembrolizumab. There were 50 patients receiving first line ICIs therapy and the other 24 received second line monotherapy. Fifty-two (83.87%, 52/62) received cisplatin among all chemotherapy patients. The median progression free survival was 10.94 months and the overall survival was 28.44 months. Poor chemotherapy response or no chemotherapy, liver metastases, Eastern Cooperative Oncology Group (ECOG) status and higher neutrophil/lymphocyte ratio (NLR) were associated with higher risk of diseases progression (HR=5.70, 95% CI 2.04-15.90, p=0.001, HR=6.08, 95% CI 1.79-20.57, p=0.004; HR=5.40, 95% CI 1.76-16.57, p=0.003; HR=6.08, 95% CI 2.56-14.44, p<0.001 and HR= 1.02, 95% CI 1.01-1.03, P=0.002 respectively). Liver metastases and WBC before ICI were associated with increased death risk (HR=11.95, 95%CI 3.22-44.34, p<0.001; HR=1.0001, 95% CI 1.00001-1.00002, p=0.036 respectively) while ICI response was associated with decreased death (HR=0.22, 95%CI 0.08-0.62, p=0.004). Chemotherapy responders were associated with better ICI treatment response (OR=6.52, 95%CI 1.45-29.24, p=0.014) while lymph node metastases and poor ECOG was associated with poor ICI response (OR=0.31, 95%CI 0.10-0.94, p=0.038; OR=0.32, 95%CI 0.11-0.95, p=0.040).Conclusions: Our data showed predictive role of first-line chemotherapy response to ICIs treatment efficacy in aUC patients as well as other prognostic factors, such as ECOG status, serum white blood cell count or NLR and liver metastases.

scholarly journals Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Yeonghak Bang ◽  
Neung Hwa Park ◽  
Jung Woo Shin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
First Line

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

scholarly journals Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis

2022 ◽  
Author(s):  
Yoshihiko Tomita ◽  
Yoshiaki Yamamoto ◽  
Norihiko Tsuchiya ◽  
Hiroomi Kanayama ◽  
Masatoshi Eto ◽  
...  
Keyword(s):  
Supportive Care ◽  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Best Supportive Care ◽  
Efficacy And Safety ◽  
First Line ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Abstract Background The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan. Methods Patients with locally advanced or metastatic UC that had not progressed with 4–6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety. Results In Japanese patients (n = 73) randomized to avelumab + BSC (n = 36) or BSC alone (n = 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8–33.0), respectively (HR, 0.81 [95% CI, 0.41–1.58]), and median PFS was 5.6 months (95% CI, 1.9–9.4) vs 1.9 months (95% CI, 1.9–3.8), respectively (HR, 0.63 [95% CI, 0.36–1.11]). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population. Conclusion Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Trial registration Clinicaltrials.gov NCT02603432.

scholarly journals A PD-1 Inhibitor Induces Complete Response of Advanced Bladder Urothelial Carcinoma: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianzheng Wang ◽  
Qingli Li ◽  
Huifang Lv ◽  
Caiyun Nie ◽  
Beibei Chen ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Complete Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Bladder Urothelial Carcinoma ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma ◽  
Mild Toxicity ◽  
First Line Treatment

The prognosis of patients with advanced urothelial carcinoma is dismal. Platinum-based chemotherapy is still the main first-line treatment for advanced urothelial carcinoma, while immunotherapy can be used as a first-line treatment option for people who cannot tolerate platinum. Immunotherapy is preferred in the second-line treatment of bladder urothelial carcinoma. PD-1 inhibitors (Pembrolizumab, nivolumab and atezolizumab) and PD-L1 inhibitors (Ddurvalumab and avelumab) have not been approved for the treatment of advanced urothelial cancer in China. We describe a patient with advanced urothelial carcinoma experienced disease progression after gemcitabine chemotherapy. Following a treatment of domestic PD-1 inhibitor (sintilimab), the patient achieved a durable complete response with mild toxicity. This case indicates that PD-1 inhibitor sintilimab might be a second-line treatment choice for advanced urothelial carcinoma.

The impact of precision medicine on real-world clinical care: A single institution retrospective study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 806-806
Author(s):  
Rajvi Patel ◽  
Ryann Quinn ◽  
Xinhua Zhu
Keyword(s):  
Retrospective Study ◽  
Precision Medicine ◽  
Real World ◽  
Clinical Care ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Genomic Profiling ◽  
Real World Data ◽  
The Impact

806 Background: In Oncology, precision medicine (PM) utilizes next generation sequencing (NGS) to analyze actionable mutations (AMs) in tumors. It is commonly done for patients (pts) with advanced cancer resistant to standard treatment. FoundationOne-CDx (F1CDx) is the only FDA approved test that utilizes NGS for genomic profiling of tumors. It is necessary to report the real-world data and its impact on clinical care. Our aim was to identify pts at our institution with AMs on F1CDx testing who received non-FDA approved targeted treatments (TT) and assess objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Methods: Retrospective study of pts at our institution from 2012 and 2018 that received non-FDA approved TT based on F1CDx testing. Descriptive statistics were used to describe the demographic and clinical characteristics. ORR based on interval scans at 3 (ORR1), 6 (ORR2), and 12 (ORR3) months (mos) were estimated using standard methods for proportions. Kaplan-Meier method was used to estimate PFS and OS. Results: Of 1000 pts, 652 had tumors harboring AMs, however, only 38 pts met study criteria of receiving non-FDA approved TT with sufficient follow up time. Median age was 57.7 years and 92% of pts received at least one prior line of therapy. Majority of the pts (58%) had gastrointestinal tumors. PDL-1, microsatellite instability, and tumor mutational burden constituted 50% of AMs and 45% of pts received TT with immunotherapy. 14/38 pts had ORR1, 12/13 pts had ORR2, and 6/7 pts had ORR3. PFS was estimated to be 2.73 mos (95% CI: 2.33 to 5.39) and OS was 9.93 mos (95% CI: 4.47 to 33.68). Conclusions: The majority of pts had progression within 3 mos of initiating TT indicating a PM approach with non-FDA approved TT may not be an effective strategy. However, a minority of pts (4 with colorectal and 1 with pancreatic cancer), derived significant benefit in achieving sustained partial response and one pt with complete response at 3 years. Although genomic profiling of tumors may be a step in the right direction, we need better and more cost effective strategies to identify pts who will truly benefit from a PM approach. More PM trials are needed to establish the standard of care to guide real-world practice.

Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with advanced urothelial carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 519-519
Author(s):  
Seung-Hoon Beom ◽  
Sun Young Rha ◽  
Joong Bae Ahn ◽  
Sang Joon Shin
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma

519 Background: Immune checkpoint inhibitors (ICI) are active in patients with advanced urothelial carcinoma which progressed to platinum-based chemotherapy. Recent data suggest that exposure to ICI improves response to salvage chemotherapy (SCT) in several cancer types. Here we evaluated whether PD-1/PD-L1 inhibitors affect the antitumor effects of SCT after ICI in patients with urothelial carcinoma. Methods: A retrospective study was conducted at Yonsei Cancer Center. Eligibility criteria were patients who received at least one SCT as 3rd-line or beyond, following progression after platinum-based chemotherapy and ICI and for whom efficacy data were available between January 2017 and September 2019. We evaluated efficacy outcomes to each therapy, including ORR by RECIST version 1.1, progression-free survival (PFS), and overall survival (OS). Results: In total, 35 patients met the inclusion criteria and were included in the analyses. ICIs were given as monotherapy and they were administrated as second-line in 48% and as later line in 52%. Twenty-six patients (74%) received a anti-PD-L1 inhibitor and 9 (26%) did a anti-PD-1 inhibitor. SCT included single paclitaxel (60%), MVAC (26%), gemcitabine/platinum combination (9%), and pemetrexed (6%). The ORR to SCT was 26%. Among 9 patients who received MVAC, 5 (55.5%) achieved a partial response. Median progression-free survival was 2.5 months and median overall survival was 7.8 months. A number of prior chemotherapy regimens was associated with response to SCT on univariate analysis. Conclusions: In urothelial cancer patients, the confirmed ORR (26%) to SCT after ICI exposure was higher as compared to historical data from the pre-ICI era. These data indicate that anti–PD-1/PD-L1 inhibitors could make tumors more vulnerable to subsequent chemotherapy.

Preliminary analysis of a phase II, multicenter, randomized, active-control study to evaluate the efficacy and safety of eganelisib (IPI 549) in combination with nivolumab compared to nivolumab monotherapy in patients with advanced urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 436-436
Author(s):  
Piotr Tomczak ◽  
Lazar Popovic ◽  
Philippe Barthelemy ◽  
Aleksander Janicic ◽  
Elena Sevillano Fernandez ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Preliminary Data ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Suppressor Cells ◽  
Progression Free Survival ◽  
Transaminase Elevation ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma ◽  
To Receive

436 Background: Inhibition of the PD-1 pathway has demonstrated clinical benefit in metastatic urothelial carcinoma (mUC); however, response rates of 15% to 29% highlight the need for more effective therapies, especially for PD-L1- patients. Eganelisib is a first-in-class, novel, oral agent which selectively inhibits PI3K-γ, with the goal of improving the immune response to checkpoint inhibitors (CPI). Methods: Eligible patients (pts) with mUC who progressed on > 1 platinum-based chemotherapy regimen and were CPI naïve were enrolled. Pts were randomized 2:1 to receive eganelisib in combination with nivolumab (EN) or placebo with nivolumab (PN). Pts were stratified by baseline circulating monocytic myeloid derived suppressor cells (mMDSC) level. The primary endpoint was objective response rate (ORR) per RECIST v1.1 in pts with high baseline mMDSC levels. Other endpoints included ORR, progression free survival (PFS) and overall survival (OS) in all pts and PD-L1 +/- pts. Results: We report preliminary data (as of 9/1/2020) for the first 49 pts with 33 randomized to receive EN and 16 PN. Preliminary ORR/PFS is presented in the table below. Except for the mMDSC high subgroup, ORR and PFS were improved in the EN arm compared to the PN arm. The duration of exposure was a median of 15 weeks for EN and 11 for PN. Most common all-Gr AEs (EN vs PN %) were pyrexia (33 vs 0), decreased appetite (30 vs 19), pruritis (24 vs 6), rash (24 vs 6), asthenia (21 vs 31), and transaminase elevation (21 vs 6). Most common Gr≥3 AEs (EN vs PN %) include hepatotoxicity (15 vs 0), transaminase elevation (12 vs 6), and rash (9 vs 0). Following an early safety review, eganelisib dose was reduced from 40 to 30 mg, resulting in a reduction of hepatic AEs. Conclusions: Preliminary data demonstrates that the combination of eganelisib, once reduced to 30 mg, and nivolumab was well tolerated with hepatic and skin-related toxicities more common in the EN arm. When compared to PN, the combination demonstrated an improved ORR and PFS, especially in the PD-L1- subset. Updated efficacy, including PFS and OS, safety and translational data will be presented. Clinical trial information: NCT03980041 . [Table: see text]

Real-World Clinical Outcomes of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

2020 ◽  
Author(s):  
Yoshifumi Kadono ◽  
Shohei Kawaguchi ◽  
Takahiro Nohara ◽  
Kazuyoshi Shigehara ◽  
Kouji Izumi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Second Line ◽  
Real World Data ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma

Abstract Background: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.Methods: The study included 98 patients with advanced UC who were treated with pembrolizumab after platinum-based chemotherapy at eight hospitals. The efficacy, safety, and risk factors for prognosis were evaluated. Results: The median age was 73 years. Nineteen patients (19%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Poor PS, liver metastasis, and higher C-reactive protein were poor prognostic factors. Hyperprogression was observed in nine patients (9%), who were mostly of poor PS and had high-volume lesions. Severe adverse events (AEs) were observed in 18 patients (19%), and five patients died because of AEs (5%). Atypical AEs, such as pneumocystis pneumonia and acute myeloid leukemia, were observed in our cohort. Conclusion: The efficacy of pembrolizumab for advanced UC in our cohort was better than a previous phase III trial (KEYNOTE-045), possibly owing to lower cancer volume and fewer visceral metastases in our patients.

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