scholarly journals A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

2019 ◽  
Vol 23 (3) ◽  
pp. 510-519 ◽  
Author(s):  
Li-Tzong Chen ◽  
Taroh Satoh ◽  
Min-Hee Ryu ◽  
Yee Chao ◽  
Ken Kato ◽  
...  
Keyword(s):  
Placebo Group ◽  
Gastroesophageal Junction ◽  
Phase 3 ◽  
Double Blind ◽  
Term Survival ◽  
Gastroesophageal Junction Cancer ◽  
Programmed Death ◽  
Previously Treated

Abstract Background Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. Methods ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. Results Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60–6.37] vs 4.14 [3.42–4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51–0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. Conclusions Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

Long-Term Survival Is Comparable between Palifermin-Treated and Placebo-Treated Patients (Pts) with Hematologic Malignancies (HM) Undergoing High-Dose Chemotherapy and Total Body Irradiation Followed by Autologous Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2925-2925 ◽  
Author(s):  
Ricardo Spielberger ◽  
Christos Emmanouilides ◽  
William Bensinger ◽  
Alan Rong ◽  
Alessandra Cesano ◽  
...  
Keyword(s):  
Controlled Study ◽  
Secondary Malignancies ◽  
Double Blind ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Double Blind Placebo ◽  
Disease Outcomes ◽  
Long Term Follow Up

Abstract Oral mucositis (OM) is a severely debilitating side effect of chemoradiotherapy that often causes significant pain, diminished quality of life, and increased risk of infections. Palifermin decreases the incidence and duration of severe OM in HM pts receiving myelotoxic therapy and HSCT. Palifermin safety and efficacy have not been established in the non-HM setting. Since the rHuKGF receptor is not expressed by HM, palifermin is not expected to interfere with long-term disease outcomes in this pt population. Aim: We assessed palifermin’s effects on the long-term disease outcomes (survival, disease progression, secondary malignancies) in pts with HM. Methods: Long-term follow-up data were pooled from a 1998 phase 2, double-blind, placebo-controlled study (n=86) and a 2000 double-blind, placebo-controlled phase 3 study (n=212). The analysis included 152 pts treated with palifermin and 146 pts treated with placebo. Pts were assessed at 6-month intervals during the first year and annually thereafter until death or loss to follow-up. The Kaplan-Meier (K–M) method provided estimates of the safety endpoints. Data reported here are as of August 2004. Results: There were 298 pts (152 palifermin: 146 placebo) monitored for long-term follow-up. The median follow-up period was 23.3 months for palifermin and 23.5 months for placebo. The overall survival and progression-free survival curves (p=0.474 and p=0.253, respectively) are similar between the palifermin and placebo groups. Secondary malignancies occurred in only 6 of 152 (3%) palifermin and 5 of 146 (4%) placebo pts. All secondary malignancies were myelodysplastic syndromes: 9 patients with diagnoses of Non-Hodgkin’s lymphoma and 2 patients of Hodgkin’s Disease. The number of deaths was similar between the groups (30% palifermin; 27% placebo); most deaths occurred within 12 months of randomization and were attributable to the underlying HM disease. Conclusion: Use of palifermin for the prevention of severe OM has shown no negative impact on long-term disease outcomes, including survival, in the HSCT setting for patients with HM.

Estimating long-term survival of PD-L1-expressing, previously treated, non-small cell lung cancer patients who received pembrolizumab in KEYNOTE-001 and -010.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 77-77 ◽  
Author(s):  
Matthew David Hellmann ◽  
Junshui Ma ◽  
Edward B. Garon ◽  
Rina Hui ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Survival Rate ◽  
Survival Models ◽  
Small Cell Lung ◽  
Stat Assoc ◽  
Term Survival ◽  
Long Term Survival ◽  
Previously Treated ◽  
Term Benefit

77 Background: Pembrolizumab showed promising activity in patients with advanced non–small cell lung cancer (NSCLC) in the KEYNOTE-001 study (NCT01295827) and significantly prolonged overall survival (OS) compared with docetaxel in the randomized KEYNOTE-010 study (NCT01905657). Responses to pembrolizumab appear to be remarkably durable, making long-term survival possible in some patients. Typical parametric survival models do not account for the possibility of long-term survival. An alternative, well-established class of statistical models called long-term survival models can be used to directly estimate the percentage of patients achieving long-term survival (>5 years), called “long-term survival rate.” (Berkson J, Gage RP. J Am Stat Assoc. 1952;47:501-515.)(Tsodikov AD et al. J Am Stat Assoc. 2003;98:1063-1078.) Methods: Data from patients with PD-L1–expressing (tumor proportion score ≥1%), previously treated, advanced NSCLC in KEYNOTE-001 and KEYNOTE-010 were used. KEYNOTE-001 data were used to initially estimate the long-term survival rate of pembrolizumab, while KEYNOTE-010 data were used for subsequent independent validation. Point estimates of long-term survival rates with their 95% CIs based on the model described above are reported. Results: Based on the long-term survival model, the estimated long-term survival rate in pembrolizumab-treated population in KEYNOTE-001 (n = 306) is 25.4% (95% CI, 15.2%-33.3%) and the intention-to-treat population who received pembrolizumab in KEYNOTE-010 (n = 690) is 25.3% (95% CI, 8.9%-36.9%). In contrast, the long-term survival rate of docetaxel arm (n = 343) in KEYNOTE-010 is estimated to be 3.2% (95% CI, 0%-17.4%). Conclusions: In 2 independent data sets, it is estimated that 25% of patients with previously treated PD-L1–expressing NSCLC may achieve long-term benefit from pembrolizumab monotherapy. Long-term survival models can provide an early estimate of long-term benefit from pembrolizumab using data with limited follow-up time. Long-term follow-up from these trials will further validate this finding. MDH and JM are co-first authors.

Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4013-4013
Author(s):  
Yelena Y. Janjigian ◽  
Akihito Kawazoe ◽  
Patricio Eduardo Yanez ◽  
Suxia Luo ◽  
Sara Lonardi ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Standard Of Care ◽  
Geographic Region ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
End Points ◽  
New Treatment ◽  
Ecog Ps

4013 Background: Trastuzumab (tras) plus chemotherapy (chemo) is standard-of-care (SOC) 1L therapy for HER2+ metastatic G/GEJ cancer. In two phase 2 studies, tras, chemo, and pembrolizumab (pembro) in combination showed promising efficacy and manageable safety. The ongoing global, randomized, double-blind, placebo-controlled phase 3 KEYNOTE-811 study is assessing whether adding pembro to SOC improves efficacy vs SOC alone for HER2+ metastatic G/GEJ cancer (NCT03615326). Methods: Eligible patients (pts) with previously untreated, unresectable or metastatic HER2+ G/GEJ cancer and ECOG PS 0 or 1 are randomized 1:1 to pembro 200 mg IV Q3W or placebo IV Q3W. All pts receive tras and investigator’s choice of 5-fluorouracil and cisplatin (FP) or capecitabine and oxaliplatin (CAPOX). Treatment is given up to 2 y or until intolerable toxicity or PD. Dual primary end points are PFS per RECIST v1.1 by blinded, independent central review (BICR) and OS. Secondary end points are ORR and DOR per RECIST v1.1 by BICR and safety. Planned enrollment in the global cohort is 692 pts; accrual is almost complete. The protocol-specified first interim analysis (IA1) was to occur when the first 260 pts enrolled had ≥8.5 mo of follow-up and tested whether pembro + SOC significantly improved ORR; the superiority boundary was P = 0.002. The ORR difference was calculated using the Miettinen and Nurminen method stratified by the randomization stratification factors of geographic region, PD-L1 status, and chemo choice. Efficacy is presented for the first 264 pts enrolled. Safety is presented for all treated pts enrolled as of Jun 17, 2020. Results: Among the first 264 pts enrolled, 133 were randomized to pembro + SOC, 131 to placebo + SOC; 0.8% had MSI-H tumors, CAPOX was chosen for 87.1%, and median study follow-up was 12.0 mo (range, 8.5-19.4). Confirmed ORR (95% CI) was 74.4% (66.2-81.6) for pembro + SOC vs 51.9% (43.0-60.7) for placebo + SOC (difference, 22.7 percentage points [95% CI, 11.2-33.7], P = 0.00006); CR rate was 11.3% vs 3.1% and DCR (95% CI) was 96.2% (91.4-98.8) vs 89.3 (82.7-94.0). Median (range) DOR was 10.6 mo (1.1+ to 16.5+) for pembro + SOC vs 9.5 mo (1.4+ to 15.4+) for placebo + SOC; KM estimates of DOR ≥6 mo and ≥9 mo were 70.3% vs 61.4% and 58.4% vs 51.1%. As of data cutoff, 433/434 enrolled pts were treated (217/217 pembro + SOC, 216/217 placebo + SOC). AEs were grade 3-5 in 57.1% of pts with pembro + SOC vs 57.4% with placebo + SOC, led to death in 3.2% vs 4.6%, and led to discontinuation of any drug in 24.4% vs 25.9%. Conclusions: Adding pembro to tras and chemo resulted in a substantial, statistically significant increase in ORR versus trastuzumab and chemo alone as 1L therapy for HER2+ metastatic G/GEJ cancer; responses were durable and safety was manageable. These initial data support pembro plus tras and chemo as a potential new treatment option for this population. Clinical trial information: NCT03615326.

scholarly journals DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Sandhia Ponnarambil ◽  
John Downie ◽  
Karin Bowen ◽  
Åsa Hellqvist ◽  
...  
Keyword(s):  
High Dose ◽  
Treatment Cessation ◽  
Uncontrolled Asthma ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Long Term Treatment ◽  
To Receive

Abstract Background Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. Methods DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. Discussion DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial registration NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

KEYNOTE-001: 3-year overall survival for patients with advanced NSCLC treated with pembrolizumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9011-9011 ◽  
Author(s):  
Natasha B. Leighl ◽  
Matthew David Hellmann ◽  
Rina Hui ◽  
Enric Carcereny Costa ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Safety Data ◽  
Current Data ◽  
Smoking History ◽  
First Line ◽  
Term Survival ◽  
Previously Treated ◽  
Nsclc Patients

9011 Background: Pembrolizumab (pembro) is approved as first-line (1L) treatment for advanced NSCLC patients (pts) with PD-L1 tumor proportion score (TPS) ≥50% and as treatment for previously treated advanced NSCLC pts with PD-L1 TPS ≥1%. Here we present 3-y OS results for pts enrolled in KEYNOTE-001 (NCT01295827), the first trial evaluating pembro in advanced NSCLC pts. Methods: 550 pts received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable toxicity, progression, or investigator or pt decision to withdraw. PD-L1 expression was assessed by IHC using the 22C3 antibody. Survival was assessed every 2 mo after treatment discontinuation. Results: 550 advanced NSCLC pts enrolled; 101 were first line (1L), and 449 were previously treated. As of the Sept 1, 2016, data cutoff, median follow-up duration was 34.5 mo (range, 25.7-51.5 mo); 8 (7.9%) 1L pts and 28 (6.2%) previously treated pts were still on treatment. 3-y OS was 26.4% (95% CI, 14.3%-40.1%) in 1L pts and 19% (95% CI, 15.0%-23.4%) in previously treated pts. 3-y OS rate and median OS by PD-L1 status are in the Table. Additional description of the pts with long-term survival, including updated safety data as well as 3-y OS by smoking history, histology, EGFRstatus, and prior radiation therapy, will be presented. Conclusions: Pembro provides promising long-term OS benefit for 1L and previously treated advanced NSCLC pts expressing PD-L1. The current data represent the longest efficacy and safety follow-up for pts with advanced NSCLC treated with pembro. Clinical trial information: NCT01295827. [Table: see text]

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