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>0.05); after treatment, life quality in SCA and CON group was significantly better than that in the DOX group (p<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.

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.

A phase III trial (ZJBIO009): CMAB009 plus irinotecan versus irinotecan alone as second-line treatment after fluoropyrimidine and oxaliplatin failure in wild-type K-ras metastatic colorectal cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3513-3513
Author(s):  
Yuankai Shi ◽  
Jin Li ◽  
Jianming Xu ◽  
Ying Cheng ◽  
Wei Liu ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Efficacy Evaluation ◽  
Open Label ◽  
Type K ◽  
Grade 3 ◽  
Colorectal Cancer Patients

3513 Background: More efficient second line treatment regimen for mCRC is urgently needed. CMAB009, a recombinant human/mouse chimeric monoclonal antibody, is specifically targeting human epidermal growth factor receptor. This study aimed to determine clinical efficacy and safety of CMAB009 plus irinotecan compared with irinotecan alone in wild-type K-ras mCRC patients (pts). Methods: This is a open-label, randomized, phase 3 trial. Patients had histologically confirmed wild-type K-ras mCRC, who previous failure of 5-fuorouracil plus oxaliplatin more than 1 month of the last-dose enrolled in study. Pts were randomly assigned on a 2:1 to receive CMAB009 (initial 400mg/m2 on day 1, and then 250 mg/m2 weekly) plus irinotecan (180mg/m2, every 2 weeks) (A arm) or irinotecan alone (B arm). B arm pts could switch to CMAB009 sequential treatment (C arm) on diseas progression. The primary end point was overall response rate (ORR). The secondary endpoints were PFS, OS, DCR, and DOR (NCT01550055). Results: From May 2009 to December 2012, 512 pts were assigned from 38 sites. Efficacy evaluation could be in 501 pts, ORR were 33.2% (112/337) and 12.8% (21/164) in A arm and B arm ( p <0.0001). C arm had 115 pts, DCR was 63.5% (73/115). DOR in A arm and B arm were 210 days and 109 days ( p=0.001). In C arm, DOR was 148 days . Median PFS was significantly longer in A arm than B arm (169 days vs 95 days; p < 0.0001). In C arm, median PFS was 84 days. Median OS was 425 days in A arm and 401 days in B arm ( p=0.94). 96.2% (484/503) pts experienced at least one adverse event (AE). 55.3%(187/338) and 37.6%(62/165) patients in A arm and B arm had at least one grade ≥3 AE respectively. The most common AE included diarrhea, emesis, leucopenia, neutropenia and fatigue. Adding CMAB009 to irinotecan increased the risk of rash (66.6% vs 5.5%, p <0.001) and paronychia (9.8% vs 0,p < 0.001). Conclusions: CMAB009 plus irinotecan significantly increased ORR and prolonged PFS compared with irinotecan alone. CMAB009 plus Irinotecan were efficient and well tolerated, which could be considered as a standard second-line treatment choice in wild-type K-ras mCRC pts. Clinical trial information: NCT01550055.

TAILOR: Phase III trial comparing erlotinib with docetaxel in the second-line treatment of NSCLC patients with wild-type (wt) EGFR.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. LBA7501-LBA7501
Author(s):  
Marina Chiara Garassino ◽  
Olga Martelli ◽  
Anna Bettini ◽  
Irene Floriani ◽  
Elena Copreni ◽  
...  
Keyword(s):  
Annual Meeting ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Daily News ◽  
Phase Iii Trial ◽  
Online Supplement ◽  
Nsclc Patients ◽  
Final Text

LBA7501 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.

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.

Phase III randomized sequential open-label study to evaluate the efficacy and safety of sorafenib followed by pazopanib versus pazopanib followed by sorafenib in the treatment of advanced/metastatic renal cell carcinoma (SWITCH-2 study).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4591-TPS4591 ◽  
Author(s):  
Juergen Gschwend ◽  
Aart Beeker ◽  
Maria de Santis ◽  
Bernhard Brehmer ◽  
Matthias R. Zaiss ◽  
...  
Keyword(s):  
Treatment Time ◽  
Research Programme ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy

TPS4591 Background: Sorafenib (SO) and pazopanib (PA) are both effective treatments for metastatic RCC (mRCC). For optimal treatment of mRCC patients (pts) it is essential to compare efficacy and safety of different sequential 1st and 2nd line treatments. The primary endpoint of this study is to evaluate if total PFS of SO followed by PA is non-inferior to PA followed by SO. Secondary objectives include time to progression during second-line treatment; time to first-line treatment failure in each arm, and PFS in first- and second-line treatment; overall survival; disease control rate in first- and second-line, safety and tolerability, and health-related quality of life. Also, a comprehensive translational research programme is integrated. Methods: Major inclusion criteria: pts with metastatic/advanced RCC not suitable for cytokines and for whom study medication constitutes first-line therapy; 18-85 years, ECOG PS 0 or 1, MSKCC score low or intermediate; at least one measurable lesion (RECIST 1.1). 544 pts will be randomized to the sequence SO→PA or PA→SO. Treatment under each drug continues until progression or intolerable toxicity. Between 1st and 2ndline therapy will be a treatment-free period of 1-4 wks. SO and PA are given in their registered doses. Pts undergo CT/MRI after every second cycle, i.e. after every 8 wks. The experimental arm will be considered to be non-inferior as long as the lower limit of the HR 95 % confidence interval (one-sided) excludes a median total PFS lower than 13.1 mos (=non inferiority margin). 383 events need to be observed to have 80% power to reject the null hypothesis of inferiority (HR ≥1.225) when the true HR=0.95. Recruitment started in June 2012. Study centers are in Germany, The Netherlands, and Austria. Clinical trial information: NCT01613846.

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]

A phase II trial comparing pemetrexed with gefitinib as the second-line treatment of nonsquamous NSCLC patients with wild-type EGFR (CTONG0806).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8042-8042 ◽  
Author(s):  
Jinji Yang ◽  
Ying Cheng ◽  
Mingfang Zhao ◽  
Qing Zhou ◽  
Hong hong Yan ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Line Setting ◽  
Nsclc Patients

8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (ORR), quality of life using the FACT-L questionnaire and safety, EGFR and K-ras mutation status were evaluated and correlated with outcomes. Results: From Feb. 2009 to Aug. 2012, 157 evaluable patients were randomized (81 cases in G arm and 76 in P arm). Baseline age, gender, and ECOG performance status were balanced between arms. The primary endpoint of PFS was met with 1.6 months for G arm versus 4.8 months for P arm, the HR is 0.51 (95% CI 0.36~0.73, P<0.001). Overall response rates were 14.7 % and 13.3 % (P=0.814) and DCR were 32.0% and 61.3% (P<0.001) for G arm and P arm, respectively. OS data were not yet mature. More skin rash and diarrhoea were seen in G arm, but more fatigue and ALT increased in P arm. CTCAE grade 3 or 4 of AEs was 12.3% in G arm and 32.9% in P arm (p=0.002). The further analyses of efficacy evaluated by IRR and biomarkers analysis will be presented on the ground. Conclusions: CTONG0806 is the first trial to show significant improvements in PFS and DCR with pemetrexed compared with gefitinib in second-line setting for advanced NSCLC with EGFR wild type. Patients with EGFR wild type did not benefit from EGFR TKI gefitinb in second-line setting. Clinical trial information: NCT00891579.

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