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.

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.

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.

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 < 0.001), and the estimated blood loss was also significantly lesser (P < 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 Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

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.

CTIM-14. RANDOMIZED PHASE II OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM). NIVOLUMAB BENEFITS OLDER POPULATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi52-vi52
Author(s):  
Manmeet Ahluwalia ◽  
David Peereboom ◽  
Yasmeen Rauf ◽  
Patrick Wen ◽  
David Reardon
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Standard Dose ◽  
Performance Status ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Dose Effect ◽  
Open Label ◽  
Anti Vegf

Abstract BACKGROUND Approaches using anti-PD1 therapy alone in rGBM is of limited efficacy. VEGF is upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. RESULTS 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall Survival was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p=0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P=0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P=0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab seem to benefit patients older than 60 years old.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 71-71
Author(s):  
Azim Jalali ◽  
Hui-Li Wong ◽  
Rachel Wong ◽  
Margaret Lee ◽  
Lucy Gately ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

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