Overall survival with everolimus, sunitinib, and placebo for advanced pancreatic neuroendocrine tumors: A matching-adjusted indirect comparison of randomized trials.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 237-237 ◽  
Author(s):  
James Signorovitch ◽  
Elyse Swallow ◽  
Evan Kantor ◽  
Xufang Wang ◽  
Peter Metrakos
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Performance Status ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Pancreatic Neuroendocrine Tumors ◽  
Early Stopping ◽  
Significant Difference ◽  
Prior Use

237 Background: Everolimus and sunitinib are approved in the US and EU for treating advanced pancreatic neuroendocrine tumors (pNET). No randomized trial has directly compared these treatments for pNET. This study indirectly compared overall survival (OS) with everolimus vs. 1) placebo and 2) sunitinib. Methods: Individual patient data were used from the RADIANT-3 trial of everolimus 10 mg/day vs. placebo (cutoff: April 4, 2010); published summary data were used from the A6181111 trial of sunitinib 37.5 mg/day vs. placebo (cutoff: June 1, 2010). To adjust for cross-trial differences, RADIANT-3 patients were subjected to exclusion criteria used in A6181111 and then re-weighted to match A6181111 in terms of baseline demographics, performance status, time since diagnosis, disease sites, distant metastases and prior therapy. After matching, OS was compared between balanced trial populations for everolimus in RADIANT-3 vs. 1) the placebo arm in A6181111, which had access to sunitinib after early stopping, and 2) the sunitinib arm in A6181111. Progression-free survival (PFS) was also assessed, but was confounded by early stopping of A6181111. Results: Analyses included 394 patients from RADIANT-3 (after excluding 15 with worse performance status than allowed in A6181111 and 1 with missing baseline data) and all 171 patients in A6181111. Before matching, patients in RADIANT-3 had better performance status, more prior use of somatostatin analogues and less prior use of systemic chemotherapy. After matching, these and all other baseline characteristics were well-balanced between trials. Everolimus was associated with prolonged OS vs. placebo in A6181111 (hazard ratio [HR] for death = 0.61, 95% CI = 0.38-0.98, p=0.04). No statistically significant difference was observed with everolimus vs. sunitinib in OS (HR for death = 0.81, 95%CI=0.49-1.31) or in PFS (HR for progression = 0.84, 95% CI=0.46-1.53). Conclusions: After adjusting for cross-trial differences, treatment of advanced pNET with everolimus was associated with prolonged OS compared to treatment with placebo.

Overall survival with everolimus, sunitinib, and placebo for advanced pancreatic neuroendocrine tumors: A matching-adjusted indirect comparison of randomized trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14621-e14621
Author(s):  
James E. Signorovitch ◽  
Elyse Swallow ◽  
Evan Kantor ◽  
Xufang Wang ◽  
Tomas Hass ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Performance Status ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Number Needed To Treat ◽  
Pancreatic Neuroendocrine Tumors ◽  
Early Stopping ◽  
Prior Use

e14621 Background: No randomized trial has compared everolimus (EVE) and sunitinib (SUN) for treatment of advanced pancreatic neuroendocrine tumors (pNET). This study indirectly compared overall survival (OS) with EVE vs. placebo (PBO), and OS and progression-free survival (PFS) with EVE vs. SUN. Methods: Individual patient data were used from the RADIANT-3 trial of EVE 10 mg/day vs. PBO (cutoff: April 2010); published summary data were used from the A6181111 trial of SUN 37.5 mg/day vs. PBO (cutoff: June 2010). To adjust for cross-trial differences, RADIANT-3 patients were subjected to A6181111 exclusion criteria and weighted to match A6181111 baseline demographics, performance status, time since diagnosis, disease sites, distant metastases and prior therapy. After matching, OS was compared between balanced trial populations for EVE vs. the PBO arm from A6181111 (which had access to SUN after progression or early stopping) and vs. the SUN arm. PFS was also compared. Analyses did not adjust for early stopping of A6181111, which may bias towards longer PFS and OS with SUN vs. PBO. Results: 394 patients from RADIANT-3 (after excluding 15 with worse performance status than allowed in A6181111 and 1 missing baseline data) and all 171 patients in A6181111 were included. RADIANT-3 patients differed from A6181111 patients in baseline performance status, prior use of somatostatin analogues, and prior use of systemic chemotherapy before matching. After matching, all baseline characteristics were well-balanced between trials. EVE was associated with significantly prolonged OS vs. PBO in A6181111 (hazard ratio [HR] for death = 0.61, 95% CI = 0.38-0.98, p=0.04), corresponding to a 1-year number needed to treat of 8.3 patients to prevent 1 death. OS and PFS were longer, but not statistically different, with EVE vs. SUN (HR for death = 0.81, 95%CI=0.49-1.31, HR for progression = 0.84, 95% CI=0.46-1.53). Conclusions: After adjusting for cross-trial differences, treatment of advanced pNET with everolimus was associated with significantly prolonged OS compared to placebo. OS and PFS were longer, but not statistically different, with everolimus compared to sunitinib.

Association of complete pathologic response after neoadjuvant chemoradiotherapy and esophagectomy with overall survival that is independent of the timing of the surgery.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 200-200
Author(s):  
Smit Singla ◽  
Moshim Kukar ◽  
Raed Alnaji ◽  
William Du ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Pathological Response ◽  
Timing Of Surgery ◽  
Survival Outcomes ◽  
Cardiac Complications ◽  
Histologic Subtype ◽  
Significant Difference

200 Background: Esophagectomy after neoadjuvant chemoradiation (nCRT) is known to improve survival outcomes, however the timing of esophagectomy is not well defined. We sought to determine if delayed esophagectomy after nCRT would result in increased likelihood of complete pathological response (cPR) and improve outcomes. Methods: A single institution analysis of all patients treated with nCRT followed by esophagectomy between 2004 and 2014. Patients were divided into four groups based on the timing of surgery (<50 days & >50 days) and pathological response (complete and incomplete), and the data was analyzed for association with survival outcomes Results: Amongst 227 patients (M: 211, F: 16; median age, 61 years) included in our study, the most common site of tumor origin was distal esophagus (n=210, 92.5%), and the most common histologic subtype was adenocarcinoma (n=205, 90.7%). Barretts esophagus was seen in 119 (52.7%), while signet cells were identified in 52 patients (22.9%) on pathology. Most patients had performance status of ECOG 0 or 1 (n=213, 93.8%), and majority of esophagectomies were performed using an open technique (n=157, 69.2%). Most esophagectomies (77.1% vs 22.9%) were performed >50 days after completion of nCRT. These patients had higher proportional incidence of anastomotic leak (11.4% vs 5.8%, p=0.302), conduit necrosis (3% vs 0%, p=0.591), need for reoperation (16% vs 9.6%, p=0.369), and pulmonary (29.7% vs 21.2%, p=0.290) and cardiac complications (18.9% vs 13.5%, p=0.415), but these increases were not significant. There was no significant difference in overall survival (OS) between the groups (median, 48.9 vs 42.6 months in <50 days and >50 days, respectively; p=0.726); however when evaluated by PR, patients with tumors with a cPR were found to have better OS compared to non-cPR (NR vs 33 months, p<0.001). When survival outcomes were compared between the timing of surgery and PR, the difference was not significant (p=0.211). Conclusions: Patients with cPR after nCRT and esophagectomy have improved overall and progression free survival, however, this is independent of the timing of the surgery.

A retrospective comparison study of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received fluoropyrimidine and platinum-based chemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 112-112 ◽  
Author(s):  
Tsuyoshi Shirakawa ◽  
Ken Kato ◽  
Naoki Takahashi ◽  
Hirokazu Shoji ◽  
Tetsuji Terazawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Febrile Neutropenia ◽  
Performance Status ◽  
Progression Free Survival ◽  
Hospital Performance ◽  
Standard Regimen ◽  
Platinum Based Chemotherapy ◽  
Significant Difference ◽  
Grade 3

112 Background: Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer (EC). Although the taxanes have shown efficacy in esophageal cancer after FP-based chemotherapy, there is no standard regimen for second-line chemotherapy (SLC). We conducted a retrospective study to investigate the clinical features of taxane therapy in SLC of EC. Methods: The selection criteria were pathologically proven EC; advanced or recurrent disease that had previously been treated with FP at our hospital; performance status 0-2; and adequate organ functions. The FP regimens used included 5-FU or S-1 and cisplatin or nedaplatin. Docetaxel (DTX) was administerd at 70mg/m2 triweekly for 6 weeks with 1 week’s rest. Paclitaxel (PTX) was administered at 100mg/m2 weekly with the same schedule. Overall survival of PTX was compared to DTX with baseline prognostic factors adjusted, using Cox proportional hazard model. Results: The analysis covered 110 patients over the period from August 2006 to June 2012. The median age was 64 years (range 39-83); 97 males and 13 females; 108 squamous cell carcinomas and 2 adenocarcinomas; 34 advanced and 76 recurrent; cStage I/II/III/IV at diagnosis 8/21/49/32; PS 0/1/2 score 20/81/9; DTX treatment 82 patients and PTX treatment 28. Progression-free survival and overall survival were 2.3 & 6.1 months with PTX and 2.8 and 6.9 months with DTX (no significant difference). The response rates were PTX/DTX/Total 11.1%/3.7%/5.5%. Hazard ratio of overall survival between DTX and PTX was 1.054 with adjusted by PS, sex and number of metastasis. The rate of grade 3-4 neutropenia was higher with DTX (28%) than with PTX (7%). Grade 3 febrile neutropenia was seen in 3.7% of DTX-treated patients but in no PTX patients. Grade 2 or more fatigue was seen in 16% of DTX patients and 10% of PTX ones, and grade 2 or more neuropathy was seen in 1.2% of DTX patients and 32% of PTX ones. Conclusions: PTX and DTX were both effective in SLC of EC, but the toxicity profiles of the two regimens differed. In terms of febrile neutropenia or fatigue, PTX seems more appropriate for SLC of EC.

scholarly journals Sunitinib-Induced Hypothyroidism and Survival in Pancreatic Neuroendocrine Tumors

2021 ◽  
Vol 53 (12) ◽  
pp. 794-800
Author(s):  
Annie Mathew ◽  
Dagmar Führer ◽  
Harald Lahner
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
Neuroendocrine Tumors ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumor ◽  
Thyroid Stimulating Hormone ◽  
Pancreatic Neuroendocrine Tumors ◽  
Tumor Patients ◽  
Free Survival

AbstractSunitinib has been approved for the treatment of pancreatic neuroendocrine tumors, renal-cell carcinoma, and gastrointestinal stromal tumors. The elevation of thyroid-stimulating hormone serum levels is a common side effect. Studies suggest a correlation between sunitinib-induced hypothyroidism and treatment outcome in patients with renal-cell carcinoma and gastrointestinal stromal tumors. This study assessed whether sunitinib-induced hypothyroidism is a predictive marker of the objective response rate, progression-free survival, and overall survival in pancreatic neuroendocrine tumor patients. Twenty-nine patients treated with sunitinib for advanced pancreatic neuroendocrine tumors were included. The incidence of sunitinib-induced hypothyroidism was 33%. The median progression-free survival of patients who developed hypothyroidism was 16 months (95% confidence interval: 6.2–25.8 months) as compared with six months among euthyroid patients (95% confidence interval: 0.1–12.2 months) (p=0.02). The median overall survival was 77 months (95% confidence interval: 31.4–122.6 months) in hypothyroid patients but 12 months (95% confidence interval: 5.9–18.1 months) in subjects with euthyroidism (p=0.001). The median overall survival from the time of initial diagnosis ranged from 247 months in patients with hypothyroidism to 65 months in euthyroid subjects (p=0.015). Elevated thyroid-stimulating hormone levels are a prognostic biomarker of improved outcomes of sunitinib therapy in pancreatic neuroendocrine tumor patients.

Retrospective analysis of glioblastoma multiforme (GBM) patients treated initially with BCNU compared to temozolomide (TMZ) with concomitant radiation therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2071-2071
Author(s):  
M. Vinjamuri ◽  
R. Adumala ◽  
R. Altaha ◽  
J. Hobbs ◽  
E. Crowell
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Retrospective Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Survival Curves ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Significant Difference

2071 Background: TMZ and radiation as initial treatment has become the standard of care for GBM. There are no randomized studies comparing TMZ to BCNU in GBM. Methods: We did a retrospective analysis of all 100 GBM patients (pts) diagnosed by our pathology department in the last 10 years. 20 pts were excluded, in 12 pts no chemotherapy was given and there was no data available for 8 pts. BCNU treatment was given in earlier years than TMZ generally. Overall survival (OS), progression free survival (PFS) and four prognostic factors were compared between BCNU and TMZ treated groups. Results: Results show that there is no significant difference in OS and PFS between the two groups. Survival curves were superimposable. This is despite the fact that tumor size and ECOG performance status were worse, though not significantly so in the BCNU group. Age was the only variable that correlated with survival. After correcting for age there was still no difference in PFS and OS between the BCNU and TMZ group. Conclusions: Our study fails to shows superiority of TMZ over BCNU despite the fact that the BCNU group had worse prognostic factors. A randomized comparison of these two agents seems justifiable. [Table: see text] No significant financial relationships to disclose.

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study

2021 ◽  
Author(s):  
Zhen Yang ◽  
Hengjun Gao ◽  
Jun Lu ◽  
Zheyu Niu ◽  
Huaqiang Zhu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Neuroendocrine Tumors ◽  
Disease Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Estimated Blood Loss ◽  
Disease Free

Abstract Objective There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. Methods Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n = 89) or regular pancreatectomy (n = 138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. Results The median follow-up period was 60.76 months in the enucleation group and 43.29 months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94 ± 42.39 min versus 217.94 ± 74.60 min, P &lt; 0.001), and the estimated blood loss was also significantly lesser (P &lt; 0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P = 0.765), and a comparable length of hospital stay (11.12 ± 3.90 days versus 9.94 ± 2.62 days, P = 0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. Conclusion Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

scholarly journals Clinical Characteristics and Prognostic Factors of Early-Onset Pancreatic Neuroendocrine Tumors

2021 ◽  
Vol 28 ◽  
pp. 107327482098682
Author(s):  
Min Shi ◽  
Biao Zhou
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Early Onset ◽  
Older Patients ◽  
Clinical Characteristics ◽  
Clinicopathological Characteristics ◽  
Pancreatic Neuroendocrine Tumors ◽  
Chi Square ◽  
Younger Patients ◽  
Significant Difference

Background: The incidence of pancreatic neuroendocrine tumors (PNETs) has increased significantly. The purpose of this study was to analyze the clinical characteristics and prognosis of patients under 50 years old. Methods: Patients with PNETs recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 were analyzed. The clinical characteristics were analyzed by Chi-square test. The Kaplan-Meier method was used to estimate overall survival (OS). Multivariate Cox proportional risk regression analysis was used to determine independent prognostic factors. Results: 2,303 patients included, of which 547 (23.8%) patients were younger than 50 years old. The number of younger patients has increased steadily, while the proportion in total PNETs decreased recently. Compared with older group, the proportion of the Black, grade I/II, and surgery were higher in early-onset PNETs. Liver was the most frequent metastatic site. There was no significant difference in the incidence of different metastatic sites between younger and older PNETs patients, while younger patients had better OS (P < 0.05). Grade, N stage, M stage, and surgery were independent prognostic factors for OS in early-onset PNETs. Conclusions: Younger patients have unique clinicopathological characteristics compared with older patients in PNETs. Better OS was observed in younger patients which might due to the higher proportion of well-differentiated tumor and surgery than older patients.

Sign in / Sign up

Export Citation Format

Share Document