One-year (yr) recurrence-free survival (RFS) from a randomized, open label phase II study of neoadjuvant (neo) talimogene laherparepvec (T-VEC) plus surgery (surgx) versus surgx for resectable stage IIIB-IVM1a melanoma (MEL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9520-9520 ◽  
Author(s):  
Reinhard Dummer ◽  
David E. Gyorki ◽  
John Robert Hyngstrom ◽  
Adam C. Berger ◽  
Robert Martin Conry ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Surgical Outcome ◽  
Distant Recurrence ◽  
Stage Iiib ◽  
Primary Analysis ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
One Year

9520 Background: We previously reported that neo T-VEC + surgx resulted in a pathologic CR rate of 21% and an OR rate of 14.7% in a randomized trial of neo T-VEC + surgx vs upfront surgx in pts with resectable stage IIIB/C/IVM1a MEL (Andtbacka et al, ASCO 2018; NCT02211131). Here, we present results from an interim 1-yr analysis of RFS. Methods: Patients (pts) with resectable stage IIIB/C/IVM1a MEL, ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions ≥ 10 mm, and no systemic tx 3 mos prior were randomized 1:1 to 6 doses/12 wks of T-VEC followed by surgx during wks 13-18 (Arm 1) vs upfront surgx during wks 1-6 (Arm 2). T-VEC was given at standard dosing until surgx, no injectable tumors, or intolerance. This analysis conducted on the ITT set estimated a between-group difference in 1-yr RFS per protocol. An RFS event was defined as the first of local, regional or distant recurrence or death due to any cause after surgx. Pts without a R0 surgical outcome or withdrew prior to surgx were considered an event at randomization for RFS. In a sensitivity analysis, RFS was calculated from randomization to the date of the first post-surgx event regardless of surgical outcome. Results: 150 pts were randomized (76 Arm 1, 74 Arm 2). Median (range) follow-up time was 20.6 (0.1, 38.5) mos in Arm 1 and 20.0 (0.1, 35.3) mos in Arm 2. 75% in Arm 1 and 93% in Arm 2 had surgx as planned. R0, R1, and R2 rates, respectively, for Arm 1 were 42.1%, 31.6%, and 1.3% and for Arm 2 were 37.8%, 51.4%, and 4.1%. At 1 yr, 33.5% of pts in Arm 1 and 21.9% of pts in Arm 2 remained recurrence free (HR 0.73, P= 0.048). From the sensitivity analysis, 55.8% of pts in Arm 1 and 39.3 % in Arm 2 remain recurrence free at 1 yr (HR 0.63, P= 0.024). OS rates at 1 yr were 95.9% in Arm 1 and 85.8% in Arm 2 (HR 0.47, P= 0.076). Pts receiving subsequent adjuvant tx was 8 (11%) in Arm 1 and 20 (29%) in Arm 2- most common was immunotherapy 6 (8.2%) and 8 (11.6%), respectively. Conclusions: In the largest randomized neo trial to date in resectable stage IIIB-IVM1a MEL, the following outcomes were improved with neo T-VEC monotherapy vs surgx: R0 surgical resections, 1-yr RFS, and OS. Primary analysis of RFS at 2 yrs is expected. Clinical trial information: NCT02211131.

scholarly journals 432 3-year results of the phase 2 randomized trial for talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery vs surgery in patients with resectable stage IIIB-IVM1a melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A458-A458
Author(s):  
Reinhard Dummer ◽  
David Gyorki ◽  
John Hyngstrom ◽  
Adam Berger ◽  
Robert Conry ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Neoadjuvant Treatment ◽  
Anticancer Therapy ◽  
Distant Recurrence ◽  
Advanced Melanoma ◽  
Stage Iiib ◽  
List Type ◽  
Talimogene Laherparepvec ◽  
Free Survival

BackgroundNeoadjuvant immunotherapies and targeted therapies for advanced melanoma are an active area of investigation. This is the first clinical trial of an approved oncolytic viral immunotherapy as a neoadjuvant treatment in advanced melanoma and the largest randomized controlled neoadjuvant trial including all types of resectable regional metastases to date. Previously published 2-year primary analysis results reported improved recurrence-free survival (RFS, HR 0.66, P=0.038) and overall survival (OS, HR 0.49, P=0.050) for neoadjuvant T-VEC plus surgery vs immediate surgery in resectable stage IIIB-IVM1a melanoma patients.1 Here, we report the 3-year interim analysis results.MethodsPatients with resectable stage IIIB-IVM1a melanoma and ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions were randomized 1:1 to receive 6 doses/12 weeks of neoadjuvant T-VEC then surgery (Arm 1) vs immediate surgical resection (Arm 2). T-VEC was administered until surgery, no remaining injectable tumors, or intolerance. RFS was defined as time from randomization to the first of local, regional, or distant recurrence, or death, where patients who did not receive surgery were imputed as events at baseline. Key secondary and exploratory endpoints include safety, an RFS sensitivity analysis that censored events at the start of subsequent anticancer therapy, OS, and event-free survival (EFS), defined as time from randomization to disease progression that precludes surgery, or local, regional or distant recurrence post-surgery, or death from any cause, whichever occurs first. All P values are descriptive. NCT02211131.ResultsAs of April 30, 2020, median follow-up for all patients was 41.3 months. For Arm 1 vs. Arm 2, the 3-year KM estimates of RFS were 46.5% vs. 31.0% (HR 0.67, P=0.043). In the RFS sensitivity analysis that removed the potential effect of subsequent anticancer therapy on RFS, the 3-year Kaplan-Meier (KM) estimates of RFS were 49.1% for Arm 1 and 22.9% for Arm 2 (HR 0.60, P=0.022). The 3-year KM estimates of EFS were 50.3% for Arm 1 and 32.7% for Arm 2 (HR 0.58, P=0.015). For OS, the 3-year KM estimates were 83.2% for Arm 1 and 71.6% for Arm 2 (HR 0.54, P=0.061). No new safety signals were detected.ConclusionsAt 3-year follow up, we continued to observe improved RFS and OS and observed improved EFS with neoadjuvant T-VEC plus surgery compared with surgery alone. These results build upon the prior 2-year results to support the treatment effect of neoadjuvant T-VEC on advanced resectable melanoma. The final analysis will occur at 5 years.Acknowledgements• The authors thank the investigators, patients, and study staff who are contributing to this study.• The study was sponsored and funded by Amgen Inc. • Medical writing support was provided by Christopher Nosala (Amgen Inc.).Trial RegistrationNCT02211131Ethics ApprovalThe study was approved by all institutional ethics boards.ReferenceDummer R, Gyorki DE, Hyngstrom J, et al. Primary 2-year (yr) results of a phase II, multicenter, randomized, open-label trial of efficacy and safety for talimogene laherparepvec (T-VEC) neoadjuvant (neo) treatment (tx) plus surgery (surg) vs surg in patients (pts) with resectable stage IIIB-IVM1a melanoma. Ann Oncol 2019;30;V903.

Updated results from the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L) or their combination (L+T) in the adjuvant treatment of HER2-positive early breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
Alvaro Moreno-Aspitia ◽  
Eileen McCormick Holmes ◽  
Christian Jackisch ◽  
Evandro De Azambuja ◽  
Frances M. Boyle ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Distant Recurrence ◽  
Phase Iii ◽  
Primary Analysis ◽  
Her2 Positive ◽  
Time To Recurrence ◽  
Long Term Follow Up ◽  
One Year ◽  
Treatment Comparisons

502 Background: Pre-specified 5-year analyses of the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial defined in Amendments 11&12. Methods: From June 2007 to July 2011, 8381 patients (pts) were randomised from 946 sites in 44 countries to receive either L+T, T→L, L, or T. In 2011, due to futility the L arm was closed and is not included in this analysis. The primary end point is disease-free survival (DFS). Secondary objectives include treatment comparisons with respect to overall survival (OS), time to recurrence (TTR), time to distant recurrence (TDR), cardiac and overall safety and tolerability. Primary analysis results of the study were published in JCO 2015 34:1034-1042. This updated analysis occurs at a 6.9 yrs median follow up (MFU). Results: All patients have reached 5-years of follow-up. 705 DFS events for L+T vs T have been observed. HR for DFS was 0.86 (95% CI, 0.74-1.00; 6-yr DFS%=85% vs 82%) for L+T vs T and 0.93 (95% CI, 0.81-1.08; 6-yr DFS%=84% vs 82%) for T→L vs. T. The 6-year OS was 93%, 92%, and 91% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T vs. T and 0.88 (95% CI, 0.71-1.08) for T→L vs. T. DFS differences for L+T vs. T were slightly higher for the hormone-receptor(ER)-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS%=84% vs. 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS%=83% vs.79%)] subgroups. There were no differences in sites of first DFS events according to treatment arm for CNS, loco-regional, or distant recurrences. There were more AEs related to study treatment (L+T 93% vs T 64%). The incidence of primary cardiac end points was low: 1% for L+T, 0.5% for T→L and 0.9% for T. Conclusions: The HRs for this updated analysis are similar to those from the Primary Analysis and the event rate remains lower than anticipated (705 vs 850 planned). Cardiac toxicity remains low. This analysis suggests that HER2+/ER- tumors may have a different biology than HER2+/ER+ and may benefit more from dual HER2 blockade. Long-term follow up continues. Clinical trial information: NCT00490139.

IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 267-267
Author(s):  
Richard S. Finn ◽  
Shukui Qin ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Treatment Benefit ◽  
Recist 1.1 ◽  
Open Label Phase ◽  
Phase Iii Study

267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial

2017 ◽  
Vol 35 (23) ◽  
pp. 2639-2646 ◽  
Author(s):  
Bent Ejlertsen ◽  
Malgorzata K. Tuxen ◽  
Erik Hugger Jakobsen ◽  
Maj-Britt Jensen ◽  
Ann Soegaard Knoop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Normal Breast ◽  
Phase Iii ◽  
Open Label ◽  
Distant Disease ◽  
Free Survival ◽  
Open Label Phase ◽  
Disease Free

Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non–anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease–free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease–free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.

Primary results from a randomized (1:1), open-label phase II study of talimogene laherparepvec (T) and ipilimumab (I) vs I alone in unresected stage IIIB- IV melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9509-9509 ◽  
Author(s):  
Jason Alan Chesney ◽  
Igor Puzanov ◽  
Merrick I. Ross ◽  
Frances A. Collichio ◽  
Mohammed M. Milhem ◽  
...  
Keyword(s):  
Oncolytic Virus ◽  
Randomized Study ◽  
Stage Iiib ◽  
Primary Analysis ◽  
Open Label ◽  
Activated T Cells ◽  
Gm Csf ◽  
Visceral Lesion ◽  
Open Label Phase ◽  
Duration Of Response

9509 Background: T is a HSV-1-based oncolytic virus designed to selectively replicate in tumors and produce GM-CSF to stimulate antitumor immune responses. I is an anti-CTLA-4 Ab that blocks inhibition of activated T cells. This is the first randomized study to evaluate the addition of an oncolytic virus to a checkpoint inhibitor. Methods: The 1o endpoint was ORR by immune-related response criteria. Key 2o endpoints: duration of response, disease control rate (DCR), PFS, OS, and safety. Prior treatment was allowed but not required. Pts had unresected stage IIIB-IV melanoma with measurable/injectable tumor(s) and no evidence of immunosuppression. T was given at approved dosing until no injectable tumors, disease progression (PD), or intolerance. I was started at w6 in T+I and at w1 in I at 3 mg/kg IV q3w x 4. Primary analysis occurred 6 m after last pt enrolled. Results: 198 pts were randomized: 98 T+I; 100 I. Characteristics were similar: 54% stage IIIB-IVM1a, 46% IVM1b/c. Median follow up time was 68 w (T+I) and 58 w (I). ORR was 38.8% (T+I) and 18.0% I, P = 0.002, Odds ratio (OR) 2.9. 89% T+I and 83% I pts remain in response. Unconfirmed visceral lesion response was 35.5% T+I vs 13.6% I. OS is immature. Of 190 pts (safety set: 95 T+I, 95 I), most common adverse events (AEs) for T+I, I (%) were fatigue (59, 42), chills (53, 3), and diarrhea (42, 35). 28% T+I and 18% I pts had gr ≥3 tx-related AE. There were 3 deaths (all unrelated) in T+I: 1 myocardial infarction and 2 PD. Conclusions: The study met the 1o endpoint. ORR was significantly higher for T+I vs I; responses were not limited to injected lesions. Toxicity of T+I combination was tolerable with no unexpected AEs. Clinical trial information: NCT01740297. [Table: see text]

Radium-223 retreatment in an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases: 2-year follow-up.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
A. Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
María José Méndez-Vidal ◽  
Daniel Keizman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Phase 1 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival ◽  
Castration Resistant ◽  
Radium 223 ◽  
Open Label Phase

178 Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating pts with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.

308 Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A335-A335
Author(s):  
Jeffrey Weber ◽  
Paolo Ascierto ◽  
Mark Middleton ◽  
Delphine Hennicken ◽  
Roberto Zoffoli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Lower Risk ◽  
Phase 3 ◽  
Free Survival ◽  
Intention To Treat ◽  
Risk Of Death ◽  
Link Type ◽  
Indirect Treatment ◽  
Resected Stage

BackgroundWe have previously performed indirect treatment comparisons (ITCs) to demonstrate improvements in recurrence-free survival (RFS) and distant metastasis-free survival with nivolumab versus placebo as adjuvant treatment for resected melanoma; however, overall survival (OS) data were not available at the time. Recently, results of the phase 3 CheckMate 238 trial in patients with resected stage IIIB–IIIC/IV melanoma (American Joint Committee on Cancer [AJCC], 7th edition) showed no statistically significant difference in OS between nivolumab and ipilimumab; however, OS events were fewer than expected. In the phase 3 EORTC 18071 trial in patients with resected stage IIIA–IIIC melanoma (AJCC, 6th edition), OS was improved with ipilimumab versus placebo. Here, we provide an update on RFS and an analysis of OS in ITCs of nivolumab and placebo using data from these 2 trials with a common comparator arm: ipilimumab 10 mg/kg.MethodsITCs of nivolumab versus placebo were conducted using 4-year minimum follow-up data from CheckMate 238 (NCT02388906) and 5.3-year median follow-up data from EORTC 18071 (NCT00636168). Bucher ITCs were performed to estimate RFS and OS in the intention-to-treat populations. A sensitivity analysis of OS adjusting for subsequent therapy options was conducted in 2 steps: (1) after controlling for possible confounders and assuming that the only difference was the effect of different subsequent therapies, postrecurrence survival was compared between the 2 ipilimumab arms in each study, and (2) after adjusting for differences in postrecurrence survival, ITCs of nivolumab versus adjusted placebo were performed.ResultsIn these ITC analyses, RFS and OS results with nivolumab suggested an improvement compared with placebo. In the intention-to-treat population, nivolumab was associated with a lower risk of recurrence or death (RFS HR, 0.55; 95% CI, 0.43–0.70) and a lower risk of death (OS HR, 0.62; 95% CI, 0.44–0.88) than placebo. In the sensitivity analysis, a 63% average increase in postrecurrence survival benefit was estimated with ipilimumab in CheckMate 238 compared with ipilimumab in EORTC 18071. After adjusting for this increase in both the ipilimumab and placebo arms in EORTC 18071, nivolumab was associated with a lower risk of death than placebo (OS HR, 0.65; 95% CI, 0.45–0.91), similar to the unadjusted analysis.ConclusionsDespite the changing treatment landscape and the increased number of therapeutic options for metastatic melanoma, these ITCs suggested clinically meaningful improvement in RFS and OS with adjuvant nivolumab compared with a wait-and-watch strategy in high-risk patients with resected melanoma.AcknowledgementsWriting and editorial assistance were provided by Kakoli Parai, PhD, and Andrea Lockett of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.Trial RegistrationNCT02388906 (CheckMate 238), NCT00636168 (EORTC 18071)

scholarly journals One-Year Progression-Free Survival of Therapy-Naive Patients With Malignant Pheochromocytoma and Paraganglioma

2013 ◽  
Vol 98 (10) ◽  
pp. 4006-4012 ◽  
Author(s):  
Ségolène Hescot ◽  
Sophie Leboulleux ◽  
Laurence Amar ◽  
Delphine Vezzosi ◽  
Isabelle Borget ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Malignant Pheochromocytoma ◽  
Inherited Disease ◽  
High Power Field ◽  
Free Survival ◽  
History Of ◽  
Wait And See ◽  
One Year

Abstract Context: The natural history of malignant pheochromocytoma or paragangliomas (MPP) remain unknown. Objective: The primary aim of this study was to define progression-free survival at 1 year in therapy-naive patients with MPP. Secondary objectives were to characterize MPP and to look for prognostic parameters for progression at 1 year. Design and Setting: The files of MPP followed up between January 2001 and January 2011 in two French Endocrine Networks were retrospectively reviewed. Therapy-naive patients were enrolled. Main Outcome Measures: The main outcome was progression-free survival at 1 year in therapy-naive MPP patients according to Response Evaluation Criteria In Solid Tumors 1.1 criteria. Results: Ninety files (46 men, 44 women, mean age of 47.5 ± 15 years) were reviewed on site by one investigator. MPP characteristics were as follows: presence of an adrenal primary, a mitotic count exceeding 5 per high power field, hypertension, inherited disease, and presence of bone metastases in 50%, 22%, 60%, 49%, and 56% patients, respectively. Fifty-seven of the 90 patients with MPP (63%) were classified as therapy-naive. The median follow-up of these 57 patients was 2.4 years (range, 0.4–5.7). At 1 year, progression-free survival was 46% (CI 95: 33–59). Twenty-six of 30 (87%) patients with progression at 1 year had exhibited progressive disease at the first imaging workup performed after a median of 5.7 months. No prognostic parameter was identified. Conclusions: Half of the therapy-naive patients with MPP achieved stable disease at 1 year. In symptom-free patients with MPP, a wait-and-see antitumor policy seems appropriate as first line. Modality for a prospective follow-up is proposed.

scholarly journals Impact of paliperidone palmitate one-month formulation on relapse prevention in patients with schizophrenia: A post-hoc analysis of a one-year, open-label study stratified by medication adherence

2018 ◽  
Vol 32 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tianmei Si ◽  
Nan Li ◽  
Huafei Lu ◽  
Shangli Cai ◽  
Jianmin Zhuo ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Hazard Ratio ◽  
Paliperidone Palmitate ◽  
Open Label ◽  
First Relapse ◽  
Continued Use ◽  
One Year ◽  
Long Acting ◽  
Post Hoc

Background: Limited data are available to help identify patients with schizophrenia who are most likely to benefit from long-acting injectable antipsychotics. Aim: To investigate the efficacy of long-acting injectable antipsychotic paliperidone palmitate one-month formulation for preventing relapses, factors influencing time to first relapse, and the effect of different antipsychotic adherence levels on time to first relapse in Chinese patients with schizophrenia. Methods: This was a post-hoc analysis from an open-label, single-arm study of stable patients (Positive and Negative Syndrome Scale total score <70; n=367) receiving paliperidone palmitate one-month formulation at the end of an acute 13-week treatment phase, who entered a naturalistic one-year follow-up period, either continuing with flexibly dosed paliperidone palmitate one-month formulation (75–150 mg eq.) or switching to another antipsychotic(s). Results: There were 362/367 patients (age=31.4±10.75 years) included in the analysis of time to first relapse (primary outcome) and 327/362 patients (39/327, poor antipsychotic adherence (<80%)) willing to receive antipsychotics were included in the exposure/adherence analysis. Overall, 84.6% (95% confidence interval=79.2–88.7) patients remained relapse-free. Poor adherence during follow-up (hazard ratio=2.97, 95% confidence interval=1.48–5.98, p=0.002) and frequent hospitalizations in the previous year (hazard ratio=1.29, 95% confidence interval=1.02–1.62, p=0.03) were associated with a significant risk of shorter time to first relapse in the univariate analysis. In patients with poor adherence, ‘no use’ (hazard ratio=13.13, 95% confidence interval=1.33–129.96, p=0.03) and ‘interrupted use’ (hazard ratio=11.04, 95% confidence interval=1.03–118.60, p=0.047) of paliperidone palmitate one-month formulation (vs continued use) showed a significantly higher risk of relapse; this was not observed in patients with good (≥80%) antipsychotic adherence. No new safety concerns were identified. Conclusion: Continued use of paliperidone palmitate one-month formulation/long-acting injectable antipsychotic was effective in preventing schizophrenia relapses, especially in patients with suboptimal antipsychotic adherence.

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