Octreotide LAR dosage and survival among elderly patients with distant-stage neuroendocrine tumors.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 392-392
Author(s):  
Chan Shen ◽  
Ya-Chen T. Shih ◽  
Ying Xu ◽  
James C. Yao
Keyword(s):  
Elderly Patients ◽  
Neuroendocrine Tumors ◽  
Dosage Level ◽  
Population Based ◽  
Rank Test ◽  
P Value ◽  
Octreotide Lar ◽  
The Difference ◽  
Long Acting ◽  
The Impact

392 Background: Octreotide long-acting repeatable (LAR) is approved for the management of symptoms due to carcinoid syndrome and may delay tumor progression among patients with neuroendocrine tumors (NETs). It is unknown whether dosage of octreotide LAR has an impact on survival. The current analysis evaluates the impact of initial octreotide LAR dosage on survival of elderly patients with NETs. Methods: Distant stage NET patients diagnosed between 1/1999 and 12/2009 who had received octreotide LAR treatment within 12 months of diagnosis were identified from the SEER-Medicare database. Those under age 65, enrolled in HMOs, or without continuous enrollment in Medicare Parts A and B were excluded. We compared the five-year survival of NET patients based on dose per 28 days averaged over the initial 3 months: Group A, <= 20 mg; B, 21 to 30 mg; C, > 30 mg. Kaplan-Meier estimations and Cox proportional hazard modeling were used to examine the association between octreotide LAR dose and survival. Results: Among 214 distant stage patients (mean and median age at 74 years old) with octreotide LAR treatment, 73 (34%) received <= 20 mg, 82 (38%) received 21 – 30 mg, while 59 (28%) received >30 mg. Median survival for patients who received low, medium and high dosage levels were 20.8 (95% CI: 13.2 – 31.5), 32.6 (95% CI: 20.5 – 51.1), and 36.3 (95% CI: 24.8 – N/A) months respectively. The log rank test had a p-value of 0.006. Multivariate analyses showed that higher octreotide LAR dosage levels were associated with significant survival improvement for distant stage patients. Compared to patients with the low dosage level, patients with medium dosage (HR=0.52, P=0.002) and patients with high dosage (HR=0.48, P=0.004) had better five-year survival. The difference in survival between Groups B and C was not statistically significant. Conclusions: This population-based study suggests potential survival benefits for octreotide LAR 30 mg dosage level among elderly distant stage NET patients.

Abstract 17276: Implantable Cardioverter-Defibrillator Therapy in Women: Population-based Outomes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Simone Cowan ◽  
Maja Grubisic ◽  
Lillian Ding ◽  
Nathaniel Hawkins ◽  
Adam Raymakers ◽  
...  
Keyword(s):  
Implantable Cardioverter Defibrillator ◽  
Survival Benefit ◽  
Heart Surgery ◽  
Population Based ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
P Value ◽  
Cardioverter Defibrillator ◽  
Operation Rate ◽  
The Impact

Background: Due to the low enrolment of women in implantable cardioverter-defibrillator (ICD) trials, there is controversy whether the survival benefit of ICDs applies to both sexes. Population-based data examining sex differences in ICD outcomes may provide further clarification. Methods: Study data were derived from a provincial registry in British Columbia (BC), the Cardiac Services BC Registry, where all ICD recipients are recorded. Patients ≥18 years with a new ICD implant from Jan 2003 to Dec 2012 were included. Data were linked to BC Vital Statistics to determine all-cause mortality. Survival was assessed using Kaplan-Meier methods stratified by sex and compared using the log-rank test. The Cox proportional-hazards model was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) between sexes. The effect of demographics, comorbidities and medication use were explored and only factors with a p-value < 0.15 were included in the final model. Statistical analyses were performed with SAS software, version 9.3 (Cary, NC). Results: There were 3905 new ICD implants; of these, 704 were women (18%). Women were younger and had a lower prevalence of comorbidities. Except for beta-blockers, women were less likely to be prescribed cardiac medications. The overall survival of women was greater than men; however, women had a higher re-operation rate for complications (Figure). After adjusting for age, diabetes, coronary artery disease, congestive cardiomyopathy, peripheral vascular disease, acquired heart surgery, and anti-arrhythmic drug use, the sex difference in mortality was attenuated, adjusted HR 0.91, (95% CI: 0.75,1.12). Conclusions: Women may derive the same survival benefit as men but have a higher re-operation rate for complications. Ongoing analyses will determine whether the impact of sex on mortality differs among patients receiving an ICD for primary versus secondary prevention.

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-Acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-Analysis of the COPE Trial

2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Rank Test ◽  
Vascular Events ◽  
Treatment Groups ◽  
Β Blocker ◽  
The Difference ◽  
Long Acting

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.

scholarly journals 177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

2021 ◽  
pp. 1167-1175
Author(s):  
Swayamjeet Satapathy ◽  
Bhagwant R. Mittal ◽  
Ashwani Sood ◽  
Apurva Sood ◽  
Rakesh Kapoor ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Octreotide Lar ◽  
Treatment Naïve ◽  
Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

scholarly journals Glycemic Control & Morbidity in Diabetics With COPD Exacerbation. A Retrospective Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A414-A414
Author(s):  
Ibrahim Naoum ◽  
Abedalghani Abedalhalim ◽  
Amir Aker ◽  
Luai Khalaili ◽  
Sameer Kassem
Keyword(s):  
Mechanical Ventilation ◽  
Glycemic Control ◽  
Population Based ◽  
Chronic Obstructive ◽  
P Value ◽  
Diabetic Patients ◽  
Copd Exacerbation ◽  
Copd Exacerbations ◽  
Significant Difference ◽  
The Impact

Abstract Background: Diabetes and chronic obstructive pulmonary disease (COPD) are widely prevalent and comorbidity with these diseases is quite common. However, there is limited data on the interrelation between glycemic control and COPD exacerbations in diabetic patients. Objective: To study the association between pre-admission glycemic control and COPD clinical outcomes including mortality, risk of hospital readmission and the need for mechanical ventilation. Methods: A retrospective population-based cohort study. We screened for patients with both diabetes and COPD exacerbation aged 35 years and above. Pre-admission glycemic control was defined by the last HBA1C level prior to hospitalization. Patients with HBA1C&gt;8% were defined as uncontrolled. We evaluated the difference between controlled and uncontrolled groups in the rates of mortality, readmission and the need for mechanical ventilation. We examined demographic and clinical parameters that might reflect COPD severity including: COPD medication use, blood hemoglobin, platelets, LDH and CRP levels. Results: 513 hospitalizations with diabetes and COPD were screened. 222 hospitalization were excluded either due to unestablished diagnosis of COPD or due to lack of HBA1C test in the preceding year. Of the remaining 291, 208 admissions were with controlled diabetes whereas 83 were uncontrolled. Although not statistically significant, the rate of re-hospitalization was higher in the uncontrolled group (OR 1.99, CI 0.99–4.0, p-value 0.051). There was no statistically significant difference in mortality (OR 1.6, CI 0.73–3.5, p-value 0.243). The use of oxygen and the need for noninvasive mechanical ventilation were significantly higher in the uncontrolled group (67.5% vs. 52.4%, p-value 0.019, 33.7% versus 18.8%, p-value 0.006, respectively). There was no significant difference in possible confounders tested between the groups. Conclusion: Uncontrolled diabetes may adversely affect patients with COPD exacerbation. Larger studies are needed to conclusively determine the impact of glycemic control on COPD morbidity and mortality.

scholarly journals Effects of Extracorporeal Membrane Oxygenation Initiation on Oxygenation and Pulmonary Opacities

2021 ◽  
Vol 7 (1) ◽  
pp. 6-13
Author(s):  
Kiran Batra ◽  
Manish Mohanka ◽  
Srinivas Bollineni ◽  
Vaidehi Kaza ◽  
Prabhakar Rajiah ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
P Value ◽  
Limited Data ◽  
Hospital Survival ◽  
Membrane Oxygenation ◽  
Pulmonary Physiology ◽  
Before And After ◽  
Laboratory Variables ◽  
The Difference ◽  
The Impact

Abstract Introduction There is limited data on the impact of extracorporeal membrane oxygenation (ECMO) on pulmonary physiology and imaging in adult patients. The current study sought to evaluate the serial changes in oxygenation and pulmonary opacities after ECMO initiation. Methods Records of patients started on veno-venous, or veno-arterial ECMO were reviewed (n=33; mean (SD): age 50(16) years; Male: Female 20:13). Clinical and laboratory variables before and after ECMO, including daily PaO2 to FiO2 ratio (PFR), were recorded. Daily chest radiographs (CXR) were prospectively appraised in a blinded fashion and scored for the extent and severity of opacities using an objective scoring system. Results ECMO was associated with impaired oxygenation as reflected by the drop in median PFR from 101 (interquartile range, IQR: 63-151) at the initiation of ECMO to a post-ECMO trough of 74 (IQR: 56-98) on post-ECMO day 5. However, the difference was not statistically significant. The appraisal of daily CXR revealed progressively worsening opacities, as reflected by a significant increase in the opacity score (Wilk’s Lambda statistic 7.59, p=0.001). During the post-ECMO period, a >10% increase in the opacity score was recorded in 93.9% of patients. There was a negative association between PFR and opacity scores, with an average one-unit decrease in the PFR corresponding to a +0.010 increase in the opacity score (95% confidence interval: 0.002 to 0.019, p-value=0.0162). The median opacity score on each day after ECMO initiation remained significantly higher than the pre-ECMO score. The most significant increase in the opacity score (9, IQR: -8 to 16) was noted on radiographs between pre-ECMO and forty-eight hours post-ECMO. The severity of deteriorating oxygenation or pulmonary opacities was not associated with hospital survival. Conclusions The use of ECMO is associated with an increase in bilateral opacities and a deterioration in oxygenation that starts early and peaks around 48 hours after ECMO initiation.

A Measure to Detect Sleep Onset Using Statistical Analysis of Spike Rhythmicity

2014 ◽  
Vol 3 (1) ◽  
pp. 27-41 ◽  
Author(s):  
B.R. Purnima ◽  
N. Sriraam ◽  
U. Krishnaswamy ◽  
K. Radhika
Keyword(s):  
Statistical Analysis ◽  
Sleep Onset ◽  
Rank Test ◽  
P Value ◽  
Sleep State ◽  
Statistical Measures ◽  
Plot Analysis ◽  
Significant Difference ◽  
Signed Rank Test ◽  
The Impact

Electroencephalogram (EEG) signals derived from polysomnography recordings play an important role in assessing the physiological and behavioral changes during onset of sleep. This paper suggests a spike rhythmicity based feature for discriminating the wake and sleep state. The polysomnography recordings are segmented into 1 second EEG patterns to ensure stationarity of the signal and four windowing scheme overlaps (0%, 50%, 60% and 75%)of EEG pattern are introduced to study the influence of the pre-processing procedure. The application of spike rhythmicity feature helps to estimate the number of spikes from the given pattern with a threshold of 25%.Then non parametric statistical analysis using Wilcoxon signed rank test is introduced to evaluate the impact of statistical measures such as mean, standard deviation, p-value and box-plot analysis under various conditions .The statistical test shows significant difference between wake and sleep with p<0.005 for the applied feature, thus demonstrating the efficiency of simple thresholding in distinguishing sleep and wake stage .

scholarly journals Poststroke Cognitive Decline: A Longitudinal Study from a Tertiary Care Center

2019 ◽  
Vol 10 (03) ◽  
pp. 459-464 ◽  
Author(s):  
Rameshwar Nath Chaurasia ◽  
Jitendra Sharma ◽  
Abhishek Pathak ◽  
Vijay Nath Mishra ◽  
Deepika Joshi
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Care Center ◽  
Tertiary Care ◽  
Rank Test ◽  
P Value ◽  
Stroke Patients ◽  
Stroke Registry ◽  
Chi Squared ◽  
The Difference

Abstract Objectives Poststroke cognitive decline (PSCD) is a serious disabling consequence of stroke. The purpose of this study is to find the prevalence of PSCD and sociodemographic and clinical determinants of risk factors of PSCD. Materials and Methods This study was a prospective, hospital-based study conducted on 200 stroke patients from stroke registry during October 2015 to April 2017. Detailed clinical evaluation was done. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were used to determine PSCD after 3 and 6 months as per the Diagnostic and Statistical Manual of Mental Disorders V. Chi-squared test was used to find the association between two variables. The Wilcoxon signed-rank test was used to compare the difference in cognitive impairment between two follow-ups at 3 and 6 months, respectively. A p-value < 0.05 was considered statistically significant. Results The prevalence of PSCD measured by MoCA scale at 3 and 6 months was 67 and 31.6%, respectively. By MMSE scale, cognitive decline prevalence at 3 months was found to be 87 (46.3%), which reduced to 22 (17.1%) at 6 months. The association between MMSE scale and type of stroke was significant at 3 months. Conclusion One-third of the stroke patients developed PSCD within 3 months of onset of stroke, with different levels of severity. The major predictors of new-onset poststroke cognitive impairment were diabetes and hypertension. The prevalence of PSCD reduced significantly at 6 months of stroke on follow-up.

The Follicular Lymphoma International Prognostic Index (FLIPI) Can Be a Useful Prognostic Indicator for Patients with Follicular Lymphoma Treated with Combination of Rituximab and Epratuzumab.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4796-4796
Author(s):  
Sandra J. Strauss ◽  
Franck Morschhauser ◽  
Martin Gramatzki ◽  
Philippe Solal-Celigny ◽  
Pier L. Zinzani ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Objective Response ◽  
Prognostic Index ◽  
Response Duration ◽  
Rank Test ◽  
P Value ◽  
Open Label ◽  
Median Response ◽  
The Impact

Abstract Background: FLIPI has been proposed as an accurate, simple, and validated prognostic index on the basis of routinely performed tests (age &gt; 60 yrs, Ann Arbor stage III-IV, serum LDH level increased, Hg &lt; 12g/dL, and more than four nodal areas involved (Solal-Céligny et al., Blood2004; 104: 1258–1265). FLIPI has reliably predicted outcome for many follicular lymphoma (FL) patients (pts) treated with chemotherapy and rituximab. Currently, monoclonal antibody (Mab) therapy and a number of radioimmunoconjugates are considered important components of the treatment of FL; therefore, evaluating FLIPI in clinical trials of these modalities is of interest for optimizing therapy. Methods: A subset analysis was performed to assess the impact of FLIPI on the outcome of patients with relapsed/refractory FL enrolled in a larger, multi-center, open label, single-arm study of epratuzumab (humanized anti-CD22 Mab) in combination with rituximab (chimeric anti-CD20 Mab) (Strauss et al., ASCO 2004). Results: A total of 32 pts with FL were treated according to this protocol (4 weekly infusions at full dose of each agent), including 16 pts who had received &gt; 2 prior chemotherapy regimens and 11 pts who had previously received rituximab. Twenty pts (62%) achieved an objective response (OR), including 8 pts (25%) with complete responses (CR, CRu) and 12 (37%) with partial responses, with a median response duration of 16.5 months (95% CI: 6.3 - 25.4) and median time-to-progression (TTP) of 11 months (95% CI: 9.9 - 19.2). Conclusion: Our data indicate that high OR rates and durable CR/CRu’s can be achieved with a combination of rituximab and epratuzumab in pts with low- (0–1) and intermediate-risk (2) FL, who failed multiple prior therapies. OR, CR rates and TTP are similar to rituximab front-line therapy for pts with low tumor burden FL (Solal-Céligny et al., Blood104: 169a, 2004). The combination of rituximab and epratuzumab was significantly less efficacious for pts with high-risk (3–5) FLIPI (P=.0.0023 for TTP). This small Phase-II study supports the prognostic value of FLIPI for pts with recurrent FL who are treated with MAbs. Prospective use of FLIPI may facilitate the optimal design of randomized trials using rituximab in combination with epratuzumab in pts with FL. Results stratified by FLIPI risk groups FLIPI score (No. of pts) OR (%) CR/CRu (%) Median Duration in months (95% CI) Median TTP in months (95% CI) TTP P-value* N/A - Not available due to patients with long TTPs that are still censored (i.e. not reached progression of disease). * - Patients with high (3–5) FLIPI scores versus others, based on the log-rank test. 0–1 (11) 9 (82) 4 (36) 15.7 (N/A) 19.2 (10.3 – 21.3) 0.0023 2 (9) 6 (67) 3 (33) 18.3 (17.2 – 25.4) 18.8 (10 – 26.7) 3–5 (12) 5 (42) 1 (8) 6.3 (N/A) 7.7 (7.1 – 10.2)

The IC50 Assay Is Predictive of Molecular Response, and Indicative of Optimal Dose in De-Novo CML Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1109-1109
Author(s):  
Deborah L White ◽  
Verity A Saunders ◽  
Thea Kalebic ◽  
Timothy P Hughes
Keyword(s):  
De Novo ◽  
Statistical Significance ◽  
Continuous Variable ◽  
Rank Test ◽  
P Value ◽  
Molecular Response ◽  
Optimization Strategy ◽  
Log Reduction ◽  
Significant Difference ◽  
The Impact

Abstract We have previously demonstrated significant interpatient variability in the IC50imatinib, a measure of the intrinsic sensitivity of a patient to imatinib induced kinase inhibition. Furthermore, this measure is predictive of the achievement of major molecular response (MMR &gt; 3 log reduction in BCR-ABL) in de-novo CML patients treated with imatinib (n=60)1. In an expanded patient pool (n=116) we now perform an evaluation of the IC50 as a predictor of response, and address the IC50imatinib as a guide to dose selection. Samples were obtained with informed consent from de novo CML patients enrolled to either the TIDEL (600mg imatinib) or TOPS (randomised 400mg vs 800mg imatinib) trials. Blood was collected pre therapy, and the IC50 was performed as previously1. Outcome data was assessed using Kaplan Meier Analysis and the log rank test was used to assess statistical significance. In our previous analysis the IC50imatinib was divided about the median value for the cohort (0.6μM) into low and high IC50, with a significantly greater proportion of patients with low IC50imatinib achieving MMR by 12 months. In this expanded patient pool, we confirm this finding (&lt;median of 0.7μM for this patient group) (low IC50 65% of patients achieve MMR by 12 mo vs high IC50 39% of patients p=0.014) Dividing the IC50’s into quartiles we now demonstrate that the IC50imatinib is a continuous variable with a greater proportion of patients in the lower quartile achieving MMR than those in the higher (Table 1 Total). Addressing the issue of dose we demonstrate that no patients with IC50&gt;0.95uM achieve MMR on 400mg, and that this is statistically significantly when compared to all other groups. At 600mg while there is no overall significant difference there is a statistically relevant difference between groups 1, 2 and 4 as indicated. In contrast, at 800 mg the effect of IC50imatinib is overcome. MMR by 12 months Total 400mg 600mg 800mg p value Group1 &lt;0.5μM 67% (27) 83% (12)* 50% (8)* 86% (7) 0.470 Group 2 &gt;0.5&lt;0.7μM 63% (30) 67% (6)* 53% (17)* 71% (7) 0.337 Group 3 &gt;0.7&lt;0.95μM 45% (31) 40%(5)* 30% (10) 56% (16) 0.139 Group 4&gt;0.95μM 32% (28) 0% (7)* 22% (9)* 58% (12) 0.016 P value 0.042 0.018 0.108 0.778 Table 1: Dividing the patients into quartile based on the IC50 imatinib and assessing the Impact of dose on the achievement of MMR by 12 month. *p value &lt;0.05 between groups (n). The failure to achieve a Complete Cytogenetic Response by 12 months is considered a suboptimal response. Assessing the molecular equivalent (≥2 log reduction in BCR-ABL) we demonstrate that a significantly greater proportion of patients with IC50imatinib&gt;0.7μM fail to achieve a 2 log reduction when treated with 400mg (IC50 &lt;0.7μM 11%: &gt;0.7μM 33% p=0.034), and 600mg (IC50 &lt;0.7μM 12%: &gt;0.7μM 22% p=0.036). However, there is no significant difference in the 800mg patient cohort (IC50 &lt;0.7μM 7%: &gt;0.7μM 14% p=0.79). This analysis confirms that the IC50imatinib, is predictive of imatinib response. Patients with an IC50imatinib &lt;0.7μM are likely to respond well to doses of 400mg imatinib, as suggested by evaluation of statistically relevant outcome benefit. In contrast patients with higher IC50imatinib (&gt;0.7μM) may benefit from higher dosing regimens (p=0.012). Thus, the accurate assessment of IC50imatinib could support dose optimization strategy for patients with a suboptimal response.

Everolimus plus octreotide LAR (E+O) versus placebo plus octreotide LAR (P+O) in patients with advanced neuroendocrine tumors (NET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-2).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 159-159 ◽  
Author(s):  
J. C. Yao ◽  
J. D. Hainsworth ◽  
E. Baudin ◽  
M. Peeters ◽  
D. Hoersch ◽  
...  
Keyword(s):  
Cox Model ◽  
Single Agent ◽  
Informative Censoring ◽  
High Rate ◽  
Phase Iii ◽  
P Value ◽  
Phase Iii Trial ◽  
Octreotide Lar ◽  
Phase Ii Studies ◽  
The Impact

159 Background: Octreotide LAR has been the foundation of NET therapy; however, additional treatment options are needed. Everolimus, an oral inhibitor of mTOR, demonstrated promising antitumor activity in patients with NET as a single agent and in combination with octreotide LAR in two phase II studies. Methods: Patients (n = 429) with well or moderately differentiated advanced NET and history of carcinoid symptoms received oral everolimus 10 mg/d + octreotide LAR 30 mg IM q 28 days (n = 216) or placebo + octreotide LAR (n = 213). Common primary sites included the small intestine, lung, and colon. The primary endpoint was progression-free survival (PFS) per central review by RECIST. Crossover from P+O to open-label E+O was allowed at disease progression. Results: Median PFS (95% CI) with E+O was 16.4 months (13.67-21.19) vs. 11.3 months (8.44-14.59) for P+O. E+O was associated with a 23% reduction in risk of progression: HR = 0.77; 95% CI: 0.59-1.00; one-sided p-value = .026 (pre-specified significance boundary is p ≤ .0246). A high rate of informative censoring resulted in loss of power in central review results. Correcting for the informative censoring bias, the pre-specified marginal Cox model using inverse probability of censoring weights (IPCW) analysis showed a significant 5.5-month improvement in median PFS with E+O; HR = 0.60; 95% CI: 0.44-0.84, with one-sided p-value = .0014. The benefit of E+O was seen across all patient subgroups. Updated analyses of the impact of pre-study and post-progression octreotide LAR therapy will be reported. Most frequent drug-related adverse events (AEs) with E+O were stomatitis, rash, fatigue, and diarrhea; mostly grade 1-2. Grade 3-4 AEs reported in >5% were stomatitis, fatigue, diarrhea, infections, and hyperglycemia. Conclusions: In this large phase III trial, E+O provided a 5.1-month clinically meaningful increase in median PFS compared with P+O in the central adjudicated review. Correcting for the informative censoring bias, a significant PFS improvement of 5.5 months was seen, with a p value = .0014. The safety profile of E+O was acceptable. [Table: see text]

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