A randomized, open-label, phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone in the second-line treatment of HER2 amplified advanced gastric cancer (AGC) in Asian population: Tytan study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 11-11 ◽  
Author(s):  
Yung-Jue Bang
Keyword(s):  
Randomized Study ◽  
Asian Population ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Open Label ◽  
Significant Prolongation ◽  
The Difference

11 Background: The use of trastuzumab has been established as the standard first-line treatment of HER2 positive (+) AGC. However, the role of anti-HER2 agents in the second-line treatment of HER2+ AGC has not been clearly established yet. TyTAN is the first randomized study to compare the efficacy and safety of adding lapatinib (L) to paclitaxel (P) vs P alone in the second-line treatment of HER2+ AGC. Methods: Eligibility required patients (pts) with AGC, amplification of HER2 by fluorescence in situ hybridization (FISH), and one prior regimen containing fluoropyrimidines and/or cisplatin. Pts were randomized 1:1 to L (1500mg QD) and P (80mg/m2, Day 1, 8, 15 q4w) or P alone. The treatments were given until disease progression or unacceptable toxicity. Stratification variables were prior trastuzumab treatment and gastrectomy status. Primary endpoint was overall survival (OS). Results: From March 2008 to June 2011, 1923 pts were screened and 430 pts were HER2+ AGC. 261 out of 430 pts were enrolled. All pts were from Asian countries: Japan (100), China (95), Korea (46), and Taiwan (20). Median OS was 11.0 months for L+P and 8.9 months for P alone in the intent-to-treat (ITT) population (HR 0.84; p=0.2088). In a pre-planned subgroup analysis, median OS in HER2 immunohistochemistry (IHC) 3+ subgroup was 14.0 months for L+P and 7.6 months for P alone (HR 0.59; p=0.0176). The endpoints in efficacy and AEs of special interest for L+P are summarized below (Table). Conclusions: Although OS was prolonged in L+P arm by 2 months, the difference was not statistically significant. HER2 IHC 3+ subgroup demonstrated statistically significant prolongation of OS by adding L. Clinical trial information: NCT00486954. [Table: see text]

Lapatinib Plus Paclitaxel Versus Paclitaxel Alone in the Second-Line Treatment ofHER2-Amplified Advanced Gastric Cancer in Asian Populations: TyTAN—A Randomized, Phase III Study

2014 ◽  
Vol 32 (19) ◽  
pp. 2039-2049 ◽  
Author(s):  
Taroh Satoh ◽  
Rui-Hua Xu ◽  
Hyun Cheol Chung ◽  
Guo-Ping Sun ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Iii ◽  
Similar Proportion ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Open Label ◽  
Significant Difference ◽  
Phase Iii Study

PurposeIn Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) –positive tumors. The role of anti-HER2 agents, including lapatinib, in this setting and population is unclear.Patients and MethodsTyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m2or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations.ResultsMedian OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%).ConclusionLapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.

Oxaliplatin Plus Irinotecan Compared With Irinotecan Alone as Second-Line Treatment After Single-Agent Fluoropyrimidine Therapy for Metastatic Colorectal Carcinoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4544-4550 ◽  
Author(s):  
Daniel G. Haller ◽  
Mace L. Rothenberg ◽  
Alfred O. Wong ◽  
Piotr M. Koralewski ◽  
Wilson H. Miller ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Sensory Disturbances ◽  
Previously Treated ◽  
Grade 3

Purpose To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. Patients and Methods A phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m2 plus oxaliplatin 85 mg/m2) or irinotecan alone (350 mg/m2) every 3 weeks. Results At the data cutoff (when 447 of 628 randomly assigned patients had died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related symptoms (32% v 19%, respectively; P = .0072) were also improved with IROX as compared with irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable between the IROX and irinotecan groups, respectively. Conclusion IROX is an effective treatment for metastatic CRC that has progressed after first-line fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone, providing an additional option in the postadjuvant or second-line treatment setting for patients who experience treatment failure with single-agent fluoropyrimidine therapy.

scholarly journals Late-line treatment in metastatic gastric cancer: today and tomorrow

2019 ◽  
Vol 11 ◽  
pp. 175883591986752 ◽  
Author(s):  
Elizabeth C. Smyth ◽  
Markus Moehler
Keyword(s):  
Gastric Cancer ◽  
Asian Population ◽  
Phase Iii ◽  
Response To Treatment ◽  
Evidence Based ◽  
Line Treatment ◽  
Second Line ◽  
Specific Patient ◽  
Line Therapy ◽  
Third Line

Survival for patients with unresectable advanced or recurrent gastric cancer (GC) remains poor and the historical lack of evidence-based therapeutic options after second-line therapy is reflected in current clinical guidelines for this condition. Despite uncertainty about optimal therapeutic strategies, further treatment is appropriate for some patients after failure of second line and may prolong survival. This approach has been reported in clinical trials and is becoming more common in real-world clinical settings. Several prognostic factors may increase the likelihood that a patient will be eligible for treatment in the third-line setting, including geographic location, status at diagnosis and response to treatment. There has been little progress over the last decade until the results from two large phase III randomized controlled trials completed in the last year: the ATTRACTION-2 trial with the programmed cell death-1 (PD-1) inhibitor, nivolumab, in an Asian population; and the TAGS trial with the oral chemotherapy trifluridine/tipiracil in a global population. Both ATTRACTION-2 and TAGS reported positive results in third-line treatment in advanced GC in specific patient groups. A further recently reported study, KEYNOTE-059, which was a single-arm phase II trial of the PD-1 inhibitor pembrolizumab in a mainly non-Asian population, has provided evidence supporting the use of this immunotherapy in patients with advanced GC. As further third-line options become available, more GC patients are expected to benefit from an individualized evidence-based approach to later-line therapy, with a common goal of extending survival and improving outcomes for their refractory disease.

scholarly journals Efficacy and Safety of Docetaxel and Sodium Cantharidinate Combination vs. Either Agent Alone as Second-Line Treatment for Advanced/Metastatic NSCLC With Wild-Type or Unknown EGFR Status: An Open-Label, Randomized Controlled, Prospective, Multi-Center Phase III Trial (Cando-L1)

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Wu ◽  
Chao Deng ◽  
Hui Zhang ◽  
Jie Weng ◽  
Youhua Wu ◽  
...  
Keyword(s):  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Metastatic Nsclc ◽  
Significant Difference ◽  
Nsclc Patients

Second-line treatment options for advanced/metastatic non-small cell lung cancer (NSCLC) patients are limited. We aimed to evaluate the efficacy and safety of docetaxel/sodium cantharidinate combination vs. either agent alone as second-line treatment for advanced/metastatic NSCLC patients with wild-type or unknown EGFR status. A randomized, open-label, phase III study was performed at 12 institutions. Patients with failure of first-line platinum regimens were randomized to receive either single-agent sodium cantharivsdinate (SCA) or single-agent docetaxel (DOX) or docetaxel/sodium cantharidinate combination (CON). The primary endpoints were centrally confirmed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. A total of 148 patients were enrolled in our study between October 2016 and March 2020. After a median follow-up time of 8.02 months, no significant difference was observed among the three groups in ORR (SCA vs. DOX vs. CON: 6.00% vs. 8.33% vs. 10.00%, respectively; p=0.814) and DCR (74.00% vs. 52.00% vs. 62.50%, respectively; p=0.080). In additional, the mOS was significantly higher in the CON group, compared with the single-agent groups (7.27 vs. 5.03 vs. 9.83 months, respectively; p=0.035), while no significant differences were observed in terms of PFS (2.7 vs. 2.9 vs. 3.1 months, respectively; p=0.740). There was no significant difference in the baseline QoL scores between the three groups (p&gt;0.05); after treatment, life quality in SCA and CON group was significantly better than that in the DOX group (p&lt;0.05). Furthermore, the incidence of adverse events (AEs) in the SCA group was significantly lower (46.00 vs. 79.17 vs. 25.00%, respectively; p=0.038) and the incidence of grade ≥3 AEs was also significantly lower in the SCA group compared with the DOX and CON groups (10.00 vs. 82.00 vs. 30.00%, respectively; p=0.042). Single-agent SCA and single-agent DOX has similar therapeutic efficacy in the second-line treatment of advanced/metastatic NSCLC with wild-type or unknown EGFR status, but single-agent SCA has fewer AEs and better QoL. Also, SCA plus DOX can significantly improve OS and exerted a significant synergistic effect, with good safety and tolerance profile.

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4666-TPS4666
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Geert-Yan Creemers ◽  
Antonio Cubillo ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

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