scholarly journals Safety and Efficacy of Everolimus in Adult Patients with Neuroendocrine Tumors

2012 ◽  
Vol 6 ◽  
pp. CMO.S7319 ◽  
Author(s):  
Paul E. Oberstein ◽  
M. Wasif Saif
Keyword(s):  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Significant Advance ◽  
Low Grade ◽  
Mtor Inhibition ◽  
Free Survival ◽  
Disease Stabilization ◽  
To Receive

Neuroendocrine tumors (NETs) consist of a diverse family of tumors which are derived from the neuroendocrine system. Most NETs are well or moderately differentiated tumors with a relatively indolent growth pattern. However, these tumors can cause significant clinical disease due to release of functional products that mediate the carcinoid syndrome and other diverse sequela. They also can grow progressively and cause symptoms from local invasion or distant metastasis. NETs are optimally treated with surgery and somatosatin analogs (SSAs) to control symptoms but are relatively insensitive to systemic chemotherapy. As a result, patients with advanced unresectable NETs have a poor prognosis. In 2011, two targeted therapies, sunitinib and everolimus were approved in the subset of progressive pancreatic NETs (pNETs). Everolimus is an oral inhibitor of the growth stimulatory mTOR pathway. In Phase 2 trials in NETs and pNETs, everolimus was well tolerated and associated with some response and widespread disease stabilization. In follow-up, randomized Phase 3 trials, everolimus was compared to placebo. In the RADIANT-2 trial, everolimus and a somatostatin analog were used in patients with functional NETs and treatment was associated with an an improvement in progression-free survival (PFS). In the RADIANT-3 trial, patients with pNET were randomized to receive everolimus or placebo along with best supportive care. Everolimus was again associated with improvement in PFS compared to placebo and it has been approved by the FDA for patients with progressive pNET. Everolimus is associated with frequent low grade toxicity but is also notable for increased rates of infection as well as non-infectious pneumonitis. mTOR inhibition with everolimus represents a significant advance in the treatment of advanced neuroendocrine tumors.

Activity of Bevacizumab in Patients With Low-Grade Serous Ovarian Carcinoma

2016 ◽  
Vol 26 (6) ◽  
pp. 1048-1052 ◽  
Author(s):  
Peter G. Rose ◽  
Haider Mahdi ◽  
Amelia Jernigan ◽  
Bin Yang
Keyword(s):  
Ovarian Carcinoma ◽  
Median Overall Survival ◽  
Single Agent ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Low Grade ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Disease Stabilization

ObjectivesThe aim of this study was to evaluate the antitumor activity of bevacizumab in low-grade serous ovarian carcinoma (LGSOC).MethodsWe retrospectively identified patients with LGSOC treated with bevacizumab.ResultsTwelve patients with LGSOC who received bevacizumab were identified. Eleven patients received bevacizumab alone. Only 1 (8.3%) of 12 patients had evidence of a partial response. Ten (90.9%) of the 11 patients were progression free at 6 months. All but 1 patient who received only 2 courses before treatment interruption had a progression-free survival (PFS) of greater than 6 months. The median PFS was 48 months (range, 5–123+ months). Three of the patients reported in this series had extended disease stabilization that lasted for 123+, 48, and 15+ months after progression-free intervals on prior chemotherapy regimens of 2.5, 4, and 7 months, respectively. The median overall survival was not reached at a median follow-up of 32 months, with only 1 of the 12 patients dying of disease.ConclusionsIn our series, in patients with LGSOC treated primarily with bevacizumab, primarily as a single agent, a low response rate but very long PFS is observed. In addition, patients have had secondary PFS durations that exceeded their prior PFS, which is a sign of anticancer activity.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5015-5015
Author(s):  
F. B. Stehman ◽  
S. Ali ◽  
D. G. Gallup ◽  
H. Key
Keyword(s):  
Cervical Carcinoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ib ◽  
Long Term Follow Up ◽  
Weekly Cycles ◽  
To Receive ◽  
Weekly Cisplatin

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p < 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p < 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.

Safety and efficacy of maintenance therapy (MT) with a nonspecific cytochrome-P 17 inhibitor (CYP17i) after response/stabilization to docetaxel in metastatic castratation-resistant prostate cancer (mCRPC) patients.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 145-145
Author(s):  
Ignacio Gil-Bazo ◽  
Ainhoa Castillo ◽  
Maria E. Zudaire ◽  
Estefania Arevalo ◽  
Omar Esteban Carranza ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Front Line ◽  
Free Survival ◽  
The Usa ◽  
Small Cohort ◽  
Daily Prednisone ◽  
To Receive

145 Background: ACRPC causes >30,000 deaths/year in the USA. The front-line treatment consists of docetaxel-based chemotherapy (D). 50% of patients (pts) show at least a 50% PSA decline during D and >15% show a partial response (R) in measurable disease. However, most of these pts present progression (P) after a median of 6-8 months (m). mCRPC remains driven by ligand-dependent androgen (A) receptor signaling. Ketoconazole (K) is a nonspecific cytochrome-P 17 inhibitor (CYP17i) able to block adrenal A synthesis. Low-dose K (LDK), (200 mg, t.d.s) has shown interesting activity in mCRPC after P to androgen deprivation therapy (ADT). The FDA recently granted approval to Abiraterone acetate, a selective CYP17i showing a survival benefit after P to D. The role of a CYP17i in the maintenance setting after response/stabilization to D has never been studied. Methods: 38 mCRPC pts starting D after P to ADT maintained LHRHa and additionally received a median of 7 cycles (3-12) of front-line three-weekly D (75 mg/m2) plus daily prednisone (10 mg). 20/38 pts showing no progression to D were enrolled. One month after the last D cycle 10 pts were assigned to MT with LDK plus prednisone (10 mg daily) and continued to receive LHRHa while the 10 pts in the control arm continued on LHRHa alone. Progression-free survival (PFS) was the primary endpoint of the study. Results: After a median follow-up of 27 m, all pts in the control arm progressed after D treatment while 8/10 pts progressed to MT. PFS from D initiation was 11.4 m for MT and 8.9 m for control arm (p=0.025). Toxicity profiles showed no significant differences between both arms. No pts discontinued LDK for toxicity reasons. Conclusions: To our knowledge, this is the first study testing a CYP17i for MT after response/stabilization to D in mCRPC. Although this is a small cohort of pts and a longer follow-up is needed, these preliminary data show a significant benefit in PFS of more than 2 months with LDK MT compared to no MT after D with a favorable toxicity profile. Thus, a further analysis in a larger series and the potential impact of this PFS benefit on the overall survival is warranted.

Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 514-514
Author(s):  
Alberto Pimentel ◽  
Abdel Karim Dip Borunda ◽  
Luis Jonathan Bueno Rosario ◽  
Gloria Martinez Martinez ◽  
Miguel Angel Pluma ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Symptom Control ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Low Grade ◽  
Common Symptom ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Long Acting

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.

Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic

2012 ◽  
Vol 117 (5) ◽  
pp. 825-830 ◽  
Author(s):  
Julia J. Compton ◽  
Nadia N. Issa Laack ◽  
Laurence J. Eckel ◽  
David A. Schomas ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Mayo Clinic ◽  
Progression Free Survival ◽  
Low Grade ◽  
Term Survival ◽  
Free Survival

Object Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. Methods Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. Results The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9–416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). Conclusions This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

scholarly journals Efficacy and safety of regorafenib versus dinutuximab with chemotherapy in Chinese children with neuroblastoma

2019 ◽  
Vol 14 (1) ◽  
pp. 32-35
Author(s):  
Kun Dong ◽  
Guan Wang ◽  
Zeng Liang Wang ◽  
Xueyan Wang
Keyword(s):  
Overall Survival ◽  
Supportive Care ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Best Supportive Care ◽  
Hazard Ratio ◽  
Chinese Children ◽  
Efficacy And Safety ◽  
Free Survival ◽  
To Receive

The objective of the present study was to evaluate the efficacy and safety of regorafenib in comparison with dinutuximab with chemotherapy in Chinese children with advanced neuroblastoma. The patients aged less than 16 years who were histologically diagnosed with advanced neuroblastoma were enrolled and randomized to receive either regorafenib plus best supportive care or dinutuximab plus chemotherapy plus best supportive care in a 1:1 ratio. The tumor response assessment was made in accordance with modified international neuroblastoma response criteria. Adverse events were also assessed. Regorafenib showed prolonged overall survival and progression-free survival than who received dinutuximab plus chemotherapy (overall survival: median 32.3 months versus 27.2 months; hazard ratio = 0.45; 95% CI 0.11-0.13, p<0.001; progression-free survival: stratified hazard ratio = 0.48; 95% CI 0.11-0.14; p<0.01).  Moreover, the overall response rate was greater in patients treated with regorafenib as compared to dinutuximab group. Regorafenib appears efficacious and has a manageable safety profile in Chinese children with advanced neuroblastoma.

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