Evaluation of safety and efficacy of somatuline autogel in combination with molecular targeted therapies (MTT) in patients with neuroendocrine tumors (NETs): Data from one Spanish cohort.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14671-e14671
Author(s):  
Jaume Capdevila ◽  
Isabel Sevilla ◽  
Vicente Alonso ◽  
Luis Anton Aparicio ◽  
Paula Jimenez ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Synergistic Effects ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Hormonal Control ◽  
Phase Iii ◽  
Free Survival ◽  
Phase Iii Studies ◽  
Spanish Cohort

e14671 Background: Analysis of the mechanisms of action of somatostatin analogs (SSAs) and mTOR inhibitors or tyrosine kinase inhibitors suggest that they may provide synergistic effects when used in combination for the treatment of pts with NETs. Methods: This is a Spanish multicenter cohort of pts with NETs treated with the SSAs lanreotide (LAN) and MTTs at 35 Spanish referral centers. Data of 159 combined treatments (133 pts) was retrospectively collected in order to evaluate the efficacy and safety of such combinations. Results: 133 pts (52,6% M) with a median age of 59,9 years; ECOG 0/1/2/3: 34%/49%/16%/1%; Lung/Pancreas/Gastrointestinal//Unknown(UK) origin: 9%/48% /32%/11%; G1/G2/G3/UK: 41%/32%/1%/26%; Non Functioning/ Functioning (69%/31%) received treatment with MTT + LAN for synergistic antiproliferative purpose in 85% of the cases, hormonal control (13,5%) or both objectives (1,5%). 115 pts received one combination treatment and 18 pts received between 2 (12 pts) and 5 (1 pt). LAN was administrated in combination with sunitinib (61), everolimus (73), bevazucimab (9), sorafenib (8) and pazopanib (8). The reported toxicity was determined by the MTT profile with no significant additional severe adverse events related to the combination with LAN. The probability of progression-free survival (PFS) at 6, 12 and 18months was 89%, 73% and 67% respectively for those pts who received LAN and sunitinib (n=50) and 78%, 69% and 57%, respectively for those pts who received LAN and everolimus (n=56). Median PFS was not reached at the time of analysis. Conclusions: The combination of LAN and MTT, mainly everolimus and sunitinib, is widely used in clinical practice without unexpected toxicities. Median PFS will be higher than data observed in phase III studies with sunitinib and everolimus, raising the hypothesis of enhanced efficacy combining SSAs and MTT that should be confirmed in randomized prospective clinical trials. [Table: see text]

scholarly journals Predictive factors of response to mTOR inhibitors in neuroendocrine tumours

2015 ◽  
Vol 23 (3) ◽  
pp. R173-R183 ◽  
Author(s):  
Maria Chiara Zatelli ◽  
Giuseppe Fanciulli ◽  
Pasqualino Malandrino ◽  
Valeria Ramundo ◽  
Antongiulio Faggiano ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Neuroendocrine Tumours ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Free Survival ◽  
Development Of Resistance ◽  
Imaging Markers ◽  
Intensive Investigation ◽  
Recent Demonstration

Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

scholarly journals Kinase Inhibitors and Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1357 ◽  
Author(s):  
Katopodis ◽  
Chudasama ◽  
Wander ◽  
Sales ◽  
Kumar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Phase Iii ◽  
Free Survival ◽  
Gynecological Malignancy ◽  
Phase Iii Trials ◽  
Chemotherapy Agents ◽  
Multiple Signaling

Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a combinatorial treatment that includes TKIs and chemotherapy agents seems promising in terms of PFS despite some adverse effects recorded; whereas the use of mTOR inhibitors seems less effective. There is a need for further research into the inhibition of multiple signaling pathways in ovarian cancer and progression to phase III trials for drugs that seem most promising.

Difference between duration of treatment (DOT) and progression-free survival (PFS) as a marker of unbalanced censoring.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2548-2548
Author(s):  
Laleh Amiri-Kordestani ◽  
Julia Wilkerson ◽  
Sanjeeve Balasubramaniam ◽  
Susan Elaine Bates ◽  
Antonio Tito Fojo
Keyword(s):  
Breast Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Clinical Trial Results ◽  
And Control ◽  
Phase Iii Studies ◽  
The Ideal

2548 Background: In the conduct of randomized trials Kaplan and Meier envisioned rates of censoring as similar between arms, providing accurate assessment of clinical trial results. Censoring is used when patients withdraw consent, leave study due to toxicity, or reach data cut-off without disease progression or death. Censoring can lead to erroneous conclusions as it can be either beneficial or detrimental to the arm under study. Such censoring can also explain how a statistically valid difference in PFS “disappears” when overall survival (OS) is examined. We hypothesized that censoring, especially that due to toxicity, would lead to a discrepancy between DOT and PFS since two different patient populations would be scored. Methods: We reviewed all phase III randomized studies of drugs approved by FDA since 2005 for pts with metastatic solid tumors, looking for DOT and PFS. We used standard statistical analyses using SAS. Results: We identified 55 Phase III studies conducted with abiraterone, axitinib, bevacizumab, cabazitaxel, cetuximab, eribulin, erlotinib, everolimus, ipilimumab, ixabepilone, lapatinib, panitumumab, pazopanib, sorafenib, sunitinib, temsirolimus and vandetinib. DOT was not provided in 27%. Forty-four comparisons (88 arms) were included in the analysis. The median PFS, DOT, delta PFS (difference in PFS between experimental and control arms) and delta DOT were: 161, 126, 51 and 36 days, respectively. The slopes of PFS vs DOT and delta PFS vs delta DOT were 1.16 and 1.03, respectively close to the ideal of 1.0. Five trials fell above the 90% CI boundary with delta PFS/delta DOT of 3 to 36, including two everolimus studies (PNET and breast cancer) two sunitinb studies (RCC and PNET) and one bevacizumab study (E2100, breast cancer). Conclusions: PFS and DOT as well as delta PFS and delta DOT should be concordant. The most likely explanation for a discordance between these values is toxicity-driven censoring and its occurrence raises concerns regarding the degree of efficacy. A greater utilization of “Time to Treatment Failure”, an endpoint that includes toxicity in its definition would be valuable in oncology trials, particularly those with high levels of toxicities.

Magenkarzinom: Kombination aus Zolbetuximab und Chemotherapie bietet neuen therapeutischen Ansatz

2021 ◽  
pp. 1-2
Author(s):  
Georg Martin Haag
Keyword(s):  
Progression Free Survival ◽  
Tumour Cells ◽  
Phase Iii ◽  
Oesophageal Adenocarcinoma ◽  
Normal Gastric Mucosa ◽  
First Line ◽  
Free Survival ◽  
Immune Effector ◽  
Grade 3 ◽  
Phase Iii Studies

<b>Background:</b> Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. <b>Patients and methods:</b> The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/m<sup>2</sup> then 600 mg/m<sup>2</sup> Q3W) (arm 2, n = 77). Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m<sup>2</sup> Q3W, n = 85). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. <b>Results:</b> In the overall population, both PFS [hazard ratio (HR) = 0.44; 95% confidence interval (CI), 0.29–0.67; P &#x3c; 0.0005] and OS (HR = 0.55; 95% CI, 0.39–0.77; P &#x3c; 0.0005) were significantly improved with zolbetuximab + EOX (arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells (HR = 0.38; 95% CI, 0.23–0.62; P &#x3c; 0.0005). Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR = 0.58; 95% CI, 0.39–0.85; P = 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1–2. Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone). <b>Conclusions:</b> In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab + EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m<sup>2</sup> is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells.

Magnitude of progression-free survival (PFS) improvement and treatment (Tx) duration in metastatic colorectal cancer (mCRC) for bevacizumab (BV) in combination with oxaliplatin-containing regimens: An analysis of two phase III studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
B. J. Giantonio ◽  
N. J. Meropol ◽  
P. J. Catalano ◽  
V. Ng ◽  
R. Oliver ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Two Phase ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Phase Iii Studies

4073 Background: In trials of BV with FOLFOX (fluorouracil, leucovorin, oxaliplatin) for mCRC, variability in the magnitude of PFS improvement has been reported [HR=0.61 in E3200 vs HR= 0.83 (FOLFOX or CAPOX (capecitabine and oxaliplatin)) in NO16966]. We propose that differences in rates of treatment discontinuation (D/C) for adverse events (AE) between these studies may have resulted in differences in the observed benefits associated with BV. We explored Tx duration (proportion of patients on Tx) and Tx D/C data at median PFS for the BV containing arms of each study. Methods: ECOG study E3200 randomized previously treated patients with mCRC to FOLFOX ± BV (10 mg/kg). NO16966 employed a 2x2 design that randomized previously untreated patients with mCRC to CAPOX vs FOLFOX and to BV (5 mg/kg) or placebo. In both trials, study Tx was defined as any component of the prescribed regimen. PFS was estimated from Kaplan-Meier curves, and hazard ratios (HR) for PFS were estimated by Cox regression. Results: Median PFS for the BV containing arm of the study: 30 weeks for E3200; 42 weeks for NO16966 Conclusion: These data suggest possible differences between the two studies in Tx duration and Tx D/C patterns with a greater proportion of patients on NO16966 discontinuing Tx for any AE. Duration of study Tx might have affected both the incidence of AEs and the magnitude of PFS benefit observed for the addition of bevacizumab to oxaliplatin-based chemotherapy in these studies. Attention to Tx duration and Non-PD Tx D/C in future clinical trials will be important when considering PFS as a primary efficacy endpoint. [Table: see text] No significant financial relationships to disclose.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study

2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  
Keyword(s):  
Performance Status ◽  
Real Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Ecog Ps ◽  
Prognostic And Predictive Markers

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

Sign in / Sign up

Export Citation Format

Share Document