Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 409-409
Author(s):  
Deniz Tural ◽  
Omer Fatih Olmez ◽  
Ahmet Taner Sümbül ◽  
Mehmet Artac ◽  
Nail Ozhan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Benefit ◽  
Progressive Disease ◽  
Univariate Analysis ◽  
First Line ◽  
Exact Test ◽  
Best Response ◽  
Metastatic Urothelial Carcinoma ◽  
Line Chemotherapy

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p <0.001). In addition, Patients with clinical benefit from first-line chemotherapy (HR= 0.39; 95% CI 0.24-0.65; p <0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factor on OS in patients' use of atezolizumab as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

scholarly journals Response to first line chemotherapy regimen is associated with efficacy of Immune Checkpoint Blockade Therapies in Patients with Metastatic Urothelial Carcinoma

2021 ◽  
Author(s):  
Deniz Tural ◽  
Fatih Selçukbiricik ◽  
Ömer Fatih Ölmez ◽  
Ahmet Taner Sümbül ◽  
Mustafa Erman ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Blockade ◽  
First Line ◽  
Kaplan Meier ◽  
Line Chemotherapy

Abstract Background Atezolizumab (ATZ) has demonstrated antitumor activity in the previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and Methods In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experience clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases (Hazard Ratio [HR] = 1.9; p = 0.04), ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. Conclusions Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy

scholarly journals Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2–Positive Metastatic Bladder Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Thomas Powles ◽  
Robert A. Huddart ◽  
Tony Elliott ◽  
Shah-Jalal Sarker ◽  
Charlotte Ackerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
First Line ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Line Chemotherapy

Purpose To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2–positive metastatic urothelial bladder cancer (UBC). Methods Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS). Results Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each). Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

Retrospective cohort study on the risk factors of admission due to serious adverse events during S-1 (tegaful, gimeracil, oteracil potassium) containing chemotherapy for gastric cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 141-141
Author(s):  
Yasuyuki Kawamoto ◽  
Satoshi Yuki ◽  
Yoshimitsu Kobayashi ◽  
Koji Oba ◽  
Hideyuki Hayashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Adverse Events ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Multivariate Logistic Regression Model ◽  
First Line ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Line Chemotherapy

141 Background: S-1 (tegaful, gimeracil, oteracil potassium) containing regimens are widely used as first line chemotherapy for metastatic or unresectable gastric cancer in Japan. Because patients often need admission due to serious adverse events (SAE) during chemotherapy, it is important to predict admission. We retrospectively investigated the risk factors of admission due to SAE during first line chemotherapy which contained S-1. Methods: We retrospectively analyzed the patients who began to receive S-1 containing chemotherapy for the first line chemotherapy at our institution from January 2005 to December 2010 by medical records. Association between baseline characteristics and admission due to SAE were evaluated by Fisher’s exact test, t-test or Mann-Whitney test. Age, sex, S-1 dose (mg/m2) and other factors which significantly associated in the univariate analysis were evaluated in the multivariate logistic regression model. Results: One hundred nine patients were assessed. Admission due to SAE were observed in 24 patients (34 times), and tended to occur before 2nd cycle had ended. Multivariate analysis suggested that hypoalbuminemia was a risk factor of admission due to all SAE (Odds ratio 0.15, 95% C.I. 0.05 - 0.44, P = 0.0005). It is suggested that S-1 dose was a risk for admission due to FU-induced colitis (Odds ratio 1.30, 95% C.I. 1.12 - 1.50, P=0.0004). Conclusions: Hypoalbuminemia might constitute a marker of admission due to SAE. FU-induced colitis occurred in S-1 dose-related fashion, and the patients had lost their weight before appropriate course. It is suggested that clinicians should pay attention to patients’ weight loss during chemotherapy, notably time of initiation of chemotherapy.

Response to first-line chemotherapy regimen to predict efficacy of nivolumab in lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3026-3026 ◽  
Author(s):  
Coureche Guillaume Kaderbhai ◽  
Corentin Richard ◽  
Jean david Fumet ◽  
Anne Aarnink ◽  
Sandra Ortiz-Cuaran ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Surrogate Marker ◽  
Chemotherapy Response ◽  
First Line ◽  
Metastatic Nsclc ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Line Chemotherapy

3026 Background: Nivolumab is a monoclonal antibody, targeting PD-1 receptor and demonstrating durable clinical benefit in 20% of metastatic NSCLC patients in second and further treatment lines. The expression of one of the PD-1 ligand, PD-L1 assessed by IHC is associated with better outcome. However, robust predictive markers of efficacy are lacking. Methods: 115 pts with stage IV NSCLC (42 squamous, 73 adenocarcinoma) were included in this retrospective study in 4 different institutions. They received nivolumab (3 mg/kg IV Q2W) after at least one line of systemic platinum-based chemotherapy. Response to first line chemotherapy and to nivolumab (RECIST 1.1) was determined on CT scan by two physicians. Association between best response to first-line regimen and PFS, OS or response to nivolumab was determined using both Chi2 and Cox analysis. Results: 46 (40%), 44 (38%) and 25 (22%) patients experimented PR, SD and PD to first-line platinum-based chemotherapy. 25 (22%), 34 (29.5%), 56 (48.5%) experimented PR, SD and PD to nivolumab. 59.5% (53/89) of patients who experimented clinical benefit (SD+PR) to first-line also experimented clinical benefit to nivolumab while only 20% (5/25) of patients with PD as best response to chemotherapy experimented clinical benefit to nivolumab (Chi2 test p = 0.002). The type of first-line doublet chemotherapy did not influence the response rate to nivolumab. Cox uni and multivariate models included age, histology and performance status underlined that patients with clinical benefit from chemotherapy had improved PFS with nivolumab (P = 0.002) (median PFS on nivolumab regimen of 4.9, 3.3 and 1.8 months for patients with PR, SD and PD to first-line, respectively). Similar results were obtained for OS (P = 0.03). Conclusions: Our data suggest that response to first-line chemotherapy may be a good surrogate marker of response, PFS and OS to post-platinum nivolumab in metastatic NSCLC.

scholarly journals A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

Blood ◽  
2017 ◽  
Vol 129 (9) ◽  
pp. 1143-1154 ◽  
Author(s):  
Steven Knapper ◽  
Nigel Russell ◽  
Amanda Gilkes ◽  
Robert K. Hills ◽  
Rosemary E. Gale ◽  
...  
Keyword(s):  
Overall Survival ◽  
Inhibitory Activity ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Newly Diagnosed ◽  
First Line ◽  
Standard Chemotherapy ◽  
Key Points ◽  
Line Chemotherapy

Key Points No overall clinical benefit was seen after the addition of lestaurtinib to standard chemotherapy for newly diagnosed FLT3-mutated AML. Lower rates of relapse and improved overall survival were seen in patients who achieved sustained levels of FLT3 inhibitory activity.

scholarly journals Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma

2020 ◽  
Vol 28 (11) ◽  
pp. 5271-5279 ◽  
Author(s):  
Shuichi Mitsunaga ◽  
Eiji Kasamatsu ◽  
Koji Machii
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cachexia ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
First Line ◽  
Timing Of Onset ◽  
Line Chemotherapy

Abstract Purpose Cachexia influences the patient’s physical wellbeing and quality of life, and the patient’s ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. Results A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. Conclusion Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

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