scholarly journals Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 525
Author(s):  
Daphne W. Dumoulin ◽  
Robin Cornelissen ◽  
Koen Bezemer ◽  
Sara J. Baart ◽  
Joachim G. J. V. Aerts
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Survival Data ◽  
Ex Vivo ◽  
Tumor Cell Line ◽  
Autologous Tumor ◽  
Term Survival ◽  
Long Term Survival ◽  
Three Phase

Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions.

Abstract 18567: Impact of Participation in Cardiac Rehabilitation on Long-term Survival after Coronary Artery Bypass Graft Surgery

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jong-Young Lee ◽  
Eun-Kyung Park ◽  
Jung-Min Ahn ◽  
Heesoon Park ◽  
Sang Soo Cheon ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Cardiac Rehabilitation ◽  
Phase I ◽  
Coronary Artery Bypass ◽  
Phase Ii ◽  
Artery Bypass ◽  
Term Survival ◽  
Long Term Survival ◽  
All Cause Mortality

Background: Although cardiac rehabilitation (CR) is recommended after coronary artery bypass grafting (CABG) surgery, there are still deficient data about the long-term benefit of CR after CABG. Methods: We analyzed a single-center prospective registry, which included patients who had undergone CABG between 2000 and 2011. We evaluated the relationship between participation in CR and long-term survival. We identified 3975 patients (62.4±9.1 years old, 74.3% male) who survived for at least 3 months after surgery. Results: Of these, 2419 (60.9%) participated in phase I of CR while hospitalized, and 383 (9.6%) participated in phase II of CR at an outpatient clinic. During a median follow-up of 6.0 years (IQR, 4.3 to 9.5), the all-cause Kaplan-Meier mortality rate was 28.8% (616 deaths). Based on the propensity score matching method, participation in phase I CR was associated with a 20% relative risk reduction in all-cause mortality (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.64 to 0.98; p=0.043) and a 40% reduction in all-cause mortality after participation in phase II CR (HR, 0.60; 95% CI, 0.40 to 0.90; p=0.012). After multivariate Cox-proportional analysis, participation in any CR phase was associated with a significant reduction in mortality (HR, 0.77; 95% CI, 0.64 to 0.93; p=0.006 in phase I CR and HR, 0.57; 95% CI, 0.39 to 0.84, p=0.004 in phase II CR). Conclusions: CR participation is associated with a significant reduction in all-cause mortality after CABG. As well as outpatient CR participation, early CR during hospitalization has a beneficial impact in reducing mortality.

Long-term survival in patients with metastatic melanoma who received ipilimumab in four phase II trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9053-9053 ◽  
Author(s):  
Celeste Lebbé ◽  
Jeffrey S. Weber ◽  
Michele Maio ◽  
Bart Neyns ◽  
Kaan Harmankaya ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Disease Progression ◽  
Phase Ii ◽  
Survival Data ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Long Term Survival

9053 Background: Ipilimumab (Ipi) has shown improved overall survival (OS) in two phase III trials of patients (pts) with metastatic melanoma (MM), with survival follow-up of >4 years in one trial. The present analyses provide survival follow-up of >5 years in four phase II trials of Ipi in MM. Methods: Pts with MM were enrolled in one of four phase II trials: (1) CA184-004, a biomarker study with Ipi at 3 or 10 mg/kg in treatment-naive (TN) and previously treated (PT) pts; (2) CA184-007, with Ipi at 10 mg/kg +/- prophylactic budesonide in TN and PT pts; (3) CA184-008, a single-arm study with Ipi at 10 mg/kg in PT pts; and (4) CA184-022, a dose-ranging study of Ipi at 0.3, 3, or 10 mg/kg in PT pts (crossover from lower dose groups to 10 mg/kg was allowed upon disease progression). Ipi was administered q3 wk x4 (induction), followed by maintenance (q12 wk from week 24) in eligible pts. Some pts were retreated with Ipi at 10 mg/kg upon disease progression. Along with survival data collected through March 2012 for studies 007, 008, and 022, we report updated 5-year OS data for study 004 collected through September 2012. Results: Five-year OS rates for TN and PT pts are reported in studies 007, 008, and 022, with combined analyses for TN and PT pts within each dose group in study 004 (Table). The results show that survival rates reach a plateau beginning at year 3. Conclusions: In pts who received Ipi at 3 or 10 mg/kg in phase II studies, regardless of prior treatment, a proportion (12.3–49.5%) remained alive 5 years after the start of treatment. These results demonstrate long-term survival with Ipi therapy in MM. An ongoing phase III trial will compare OS for Ipi at 3 vs 10 mg/kg in pts with MM. Clinical trial information: NCT00162123. [Table: see text]

Effect of ipilimumab treatment on 18-month survival: Update of patients (pts) with advanced melanoma treated with 10 mg/kg ipilimumab in three phase II clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9033-9033
Author(s):  
S. O'Day ◽  
J. Weber ◽  
C. Lebbe ◽  
M. Maio ◽  
H. Pehamberger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Survival Benefit ◽  
Survival Rates ◽  
Advanced Melanoma ◽  
Controlled Study ◽  
Term Survival ◽  
Long Term Survival

9033 Background: The monoclonal antibody ipilimumab targets cytotoxic T lymphocyte antigen-4. Updated survival data (≤32.5 months follow-up) from 3 Phase II trials of ipilimumab in pts with mostly pretreated advanced melanoma are reported. Methods: Study CA184008 was an open-label, single-arm study of ipilimumab 10 mg/kg. Study CA184022 was a randomized, dose-ranging study of ipilimumab 0.3, 3, or 10 mg/kg. Study CA184007 was a randomized, placebo-controlled study of the effect of budesonide on gastrointestinal immune-related adverse events in pts receiving ipilimumab 10 mg/kg. In all studies, ipilimumab was given every 3 weeks (Q3W) × 4 (induction); eligible pts could continue to receive maintenance ipilimumab Q12W from week 24. Pts continue to be followed-up to determine long-term survival. Results: With a median follow-up ranging from 10.1 to 16.3 months and reaching up to 32.5+ months, pts receiving 10 mg/kg ipilimumab showed durable survival; 12- and 18-month survival rates are presented [ Table ]. The tail of the Kaplan-Meier curve flattened at 18 months, indicating that a substantial proportion of patients continued to survive beyond the updated follow-up period in all three studies. Long-term survivors include pts with disease progression (PD) per modified World Health Organization (mWHO) criteria. Conclusions: Ipilimumab may result in a long-term survival benefit in pts with advanced melanoma, where 18-month survival rates across 3 Phase II studies range from 34.5% to 39.4% for previously treated pts. These results indicate that more than 1/3 of ipilimumab-treated pts with advanced melanoma experience a long-term survival benefit, including some pts characterized as PD by mWHO. The survival data continue to mature, and follow-up is ongoing. [Table: see text] [Table: see text]

scholarly journals Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3390
Author(s):  
Mats Enlund
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Retrospective Studies ◽  
Breast Cancer Surgery ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Long Term Survival ◽  
Significant Difference ◽  
One Year

Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

scholarly journals Long-term survival data from a clinical trial on resin-bonded bridges

1997 ◽  
Vol 25 (3-4) ◽  
pp. 239-242 ◽  
Author(s):  
N.H.J. Creugers ◽  
R.J.A.M. De Kanter ◽  
M.A. van't Hof
Keyword(s):  
Clinical Trial ◽  
Survival Data ◽  
Term Survival ◽  
Long Term Survival

CURE OF THREE PATIENTS WHO HAD SKELETAL METASTASES IN DISSEMINATED NEUROBLASTOMA

PEDIATRICS ◽  
1968 ◽  
Vol 41 (1) ◽  
pp. 47-51
Author(s):  
Douglas Reilly ◽  
Mark E. Nesbit ◽  
William Krivit
Keyword(s):  
Overall Survival ◽  
Survival Data ◽  
Specific Treatment ◽  
Skeletal Metastases ◽  
University Of Minnesota ◽  
Term Survival ◽  
Long Term Survival ◽  
Skeletal Involvement ◽  
The University

The long-term survival of three children with disseminated skeletal metastases due to neuroblastoma is reported. These three patients are added to eight other patients reported in the literature who have survived longer than 2 years after the development of their metastatic osseous lesions. A review of the cases did not reveal a specific treatment regime which provided the success in these cases. The presence of skeletal involvement, therefore, should not indicate a hopeless prognosis. A review of 33 patients with neuroblastoma at the University of Minnesota from 1956-1966 is also given to provide overall survival data.

Identification of characteristics associated with long-term survival in patients with metastatic urothelial carcinoma (mUC) who received durvalumab (D) with or without tremelimumab (T) in clinical studies.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 441-441
Author(s):  
Marie Alt ◽  
Carlos Stecca ◽  
Shaum Kabadi ◽  
Benga Kazeem ◽  
Srikala S. Sridhar
Keyword(s):  
Logistic Regression ◽  
Phase I ◽  
Regression Model ◽  
Clinical Studies ◽  
Logistic Regression Model ◽  
Multivariate Logistic Regression Model ◽  
Multivariate Logistic Regression ◽  
Term Survival ◽  
Long Term Survival

441 Background: Immune checkpoint inhibitors (ICI) have changed the landscape of mUC, yet outcomes are variable as some patients (pts) do not respond to treatment while others have a durable response. To optimally select pts who may derive benefit from ICIs, predictive factors are required. This retrospective, post-hoc analysis evaluated pt characteristics to determine differences between short and long-term survivors among pts with mUC who received D (anti–PD-L1) with or without T (anti–CTLA-4) in two clinical studies. Methods: Pts with platinum-refractory mUC who received D monotherapy in the phase I/II study 1108 (10 mg/kg Q2W, up to 12 mo) or D+T in the phase I study 10 (D at 20 mg/kg + T at 1 mg/kg Q4W for 4 mo, then D at 10 mg/kg Q2W for 12 mo) were included. Pt characteristics, tumor characteristics, radiological assessments, and biological assessments were collected. The primary outcome measure was long-term overall survival (OS). Pts were categorized as OS ≥2 yrs (from 1st dose of study drug) or OS <2 yrs. A univariate analysis was conducted on each baseline characteristic to assess independent associations with long-term OS; a multivariate logistic regression model was employed including each variable with a p-value ≤0.1 as factors or covariates. Results: A total of 367 pts with mUC were included in the analysis: 88 (24.0%) had OS ≥2 yrs (range: 2.09–4.99) and 279 (76.0%) had OS <2 yrs (range: 0.03–1.98). Pts with OS ≥2 yrs had a significantly higher objective response rates than those with OS <2 yrs (71.6% vs 5.7%; p<0.0001) and a significantly longer duration of response (median 2.3 yrs vs 0.39 yrs; p<0.0001). The characteristics included in the multivariate logistic regression model are listed in the Table. Long-term OS was significantly associated with ECOG PS, PD-L1 status, baseline hemoglobin level, and baseline absolute neutrophils count. Conclusions: Our analyses show that several characteristics, including tumor response to treatment, are associated with long-term OS for pts with mUC treated with D or D+T. Further investigation into these and other characteristics may provide additional insights into long-term survival outcomes with ICIs. [Table: see text]

scholarly journals Evolving impact of long-term survival results on metastatic melanoma treatment

2020 ◽  
Vol 8 (2) ◽  
pp. e000948 ◽  
Author(s):  
Olivier Michielin ◽  
Michael B Atkins ◽  
Henry B Koon ◽  
Reinhard Dummer ◽  
Paolo Antonio Ascierto
Keyword(s):  
Targeted Therapies ◽  
Survival Data ◽  
Long Term Results ◽  
Tumor Type ◽  
Term Survival ◽  
Long Term Survival ◽  
The Past ◽  
Number Of Patients ◽  
Melanoma Treatment

Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

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