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.

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.

Survival outcome segregated by KRAS mutation status in newly diagnosed stage IV non-small cell lung cancer (NSCLC) patients (pts) treated with first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
Anna K. Brady ◽  
Jonathan D McNeill ◽  
Brendan Judy ◽  
Tracey L. Evans ◽  
Roger B. Cohen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Predictive Marker ◽  
Smoking History ◽  
Newly Diagnosed ◽  
First Line ◽  
Kras Mutations ◽  
Line Chemotherapy

7595 Background: KRAS mutations (MT) form a distinct subset of NSCLC, generally considered to have poor prognosis. Although KRAS MT is a well-establised prognostic and predictive marker in colorectal cancer, its role in NSCLC remains ambiguous. Pts with KRAS MT NSCLC do not respond well to epidermal growth factor receptor (EGFR) directed tyrosine kinase inhibitor therapy, but little is known about the ability of KRAS MT to predict outcome after first-line chemotherapy in newly diagnosed advanced or recurrent NSCLC. Methods: We analyzed outcomes of consecutive pts with newly identified Stage IV non- squamous NSCLC treated at University of Pennsylvania (Penn) between 05/2008 and 7/2010 and then compared survival based on KRAS status [MT vs wild type (WT)] using chi square, Kaplan-Meier methods, and Cox regression models. Results: Of 106 consecutive new pts with Stage IV non squamous NSCLC treated at Penn, 49 (46%) underwent molecular analysis for KRAS MT. Fifteen (34%) were KRAS MT. Of 34 KRAS WT pts, 6 were positive for EGFR MT. The median age of all 49 pts was 61 years; 83% were Caucasian, 45% male and 60% had a >10 pack year smoking history. Median duration of follow up is 16.4 mos. Majority of pts (92%) had adenocarcinoma histology. Most pts (88%) had ECOG PS 0-1 at presentation. Forty three pts received first line platinum-based combination chemotherapy (platinum and pemetrexed in 31 pts). KRAS MT was associated with smoking (p=0.04), but not with gender or age. Overall survival (OS) of pts with KRAS MT was similar to KRAS WT pts [median OS 15.6 vs. 19.0 mos; HR 1.24 (95% CI 0.57-2.67)]. Univariate analyses demonstrated superior OS among women compared to men (HR 0.40, 95% CI 0.20-0.85) in the entire pt cohort. Conclusions: In our population of stage IV non squamous NSCLC, pts with KRAS MT had similar OS to those with KRAS WT tumors. OS was slightly higher in KRAS WT pts, but this may have been confounded by the inclusion of 6 EGFR MT pts in this cohort. The potential prognostic or predictive role of KRAS MT in NSCLC pts undergoing chemotherapy requires further prospective study.

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.

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

Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

2005 ◽  
Vol 23 (33) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ruth E. Langley ◽  
James Carmichael ◽  
Alison L. Jones ◽  
David A. Cameron ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Time ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
De Novo Aml

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.

scholarly journals P08.06 Clinical value scores for treatment of newly diagnosed glioblastoma with TTFields

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii38-iii38
Author(s):  
J Kelly ◽  
C Proescholdt
Keyword(s):  
Overall Survival ◽  
Cancer Treatment ◽  
Clinical Benefit ◽  
Health Benefit ◽  
Value Assessment ◽  
Toxicity Profile ◽  
Newly Diagnosed ◽  
Clinical Value ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND High quality and value of recommended treatments is of specific importance in cancer care. ESMO, ASCO and NCCN have developed tools intended to help assessing the clinical value of cancer treatments in a standardised way, allowing for a comparative discussion. Tumor treating fields (TTFields) is a novel, device based cancer treatment, that was recently demonstrated to be effective in newly diagnosed glioblastoma (GBM). This new modality augments the treatments discussed with glioblastoma patients today. MATERIAL AND METHODS ESMO and ASCO frameworks each calculate a score for the clinical value of a cancer treatment, called Magnitude of Clinical Benefit Scale (MCBS) by ESMO and the Net Health Benefit (NHB) by ASCO. NCCN self reports “evidence blocks” which are assessed by clinician panels and were recently published for the first line treatment of newly diagnosed GBM with TTFields. We apply and compare the ESMO, ASCO and NCCN tools for TTFields treatment of newly diagnosed GBM. RESULTS The resulting ASCO NHB score for TTFields treatment of newly diagnosed GBM is 56. ESMO MCBS scores for TTFields in GBM are resulting in A/5, these being the highest achievable scores for this framework. All frameworks value the increase in overall survival by TTFields and the moderate toxicity profile. ESMO additionally values quality of life, while ASCO values palliation and treatment free intervals. NCCN’s specific focus is on the quality and consistency of the evidence. NCCN evidence blocks also contain an affordability score. CONCLUSION All three frameworks consider the clinical efficacy of a treatment and it’s toxicity profile in their clinical value assessment. Beyond that, their respective focus is on slightly different aspects and their definition of clinical value therefore varies in detail. However, all value scores suggest that TTFields treatment of newly diagnosed GBM provides a substantial clinical benefit. The high ESMO and ASCO scores are based on the significantly extended progression free and overall survival for TTFields treated patients, without adding systemic toxicities. The NCCN evidence blocks strongly support the NCCN category 1 recommendation for the use of TTFields in newly diagnosed GBM.

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