Update results of paclitaxel and cisplatin in combination with anlotinib as first-line regimen for advanced esophageal squamous cell carcinoma (ESCC): A multicenter, single-arm, open-label phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 181-181
Author(s):  
Junsheng Wang ◽  
Suxia Luo ◽  
Ning Li ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Locally Advanced ◽  
Response Assessment ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy

181 Background: The prognosis of pts with advanced ESCC remains dismal clinically. Paclitaxel and cisplatin were used as the standard first-line regimen in ESCC for almost two decades. As a novel multitarget tyrosine kinase inhibitor mainly targeting antiangiogenic single pathway, anlotinib was demonstrated to be an effective second-line monotherapy for pts with advanced or recurrent ESCC in China. Consequently, the aim of this study was to investigate the efficacy and toxicity of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC. Methods: Pts with previously untreated metastatic or unresectable, locally advanced ESCC, who had not received (neo) adjuvant therapy/radical surgery within 6 months were recruited in this study. Eligible subjects were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 4~6 cycles during initial therapy. For those without progressive disease, maintenance treatment was administrated with anlotinib monotherapy (10mg, po, d1~14, q3w) until progression or unacceptable toxicity. The tumor response was assessed by investigator according to RECIST version 1.1 using CT scans every two cycles. And the calculated sample size of this study was 47. The primary endpoint was PFS, secondary endpoints were safety, objective response rate (ORR), disease control rate (DCR) and duration of response (DOR). Results: From Oct 2019 to Aug 2020, 27 pts were available for efficacy and safety evaluation. In best overall response assessment, there were 7.4% CR (2/27), 66.7% PR (18/27) and 25.9% SD (7/27). ORR was 74.1% (95%CI: 53.7. ~ 88.9), and DCR was 100.0% (95%CI: 87.2~100.0). The median PFS of the 27 pts was not yet available. The safety profile indicated that the most common drug-related adverse events were myelosuppression, gastrointestinal reaction, fatigue, hypertension, constipation, hypokalemia and hepatotoxicity. The common grade 3-4 treatment-related adverse events were myelosuppression (18.5%), hypertension (7.4%). Conclusions: The current results indicated that paclitaxel and cisplatin combined with anlotinib as first line therapy for advanced ESCC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more pts consecutively. Clinical trial information: NCT04063683. [Table: see text]

Update results of paclitaxel and cisplatin in combination with anlotinib as first-line regimen for patients with advanced ESCC: A multicenter, single-arm, open-label phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16013-e16013
Author(s):  
Junsheng Wang ◽  
Tao Wu ◽  
Suxia Luo ◽  
Ning Li ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Safety Profile ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Common

e16013 Background: Paclitaxel combined with cisplatin regimen has been the standard first-line therapy in advanced Esophageal Squamous Cell Carcinoma (ESCC) for almost two decades. However, the 5-year survival rate was only 4.8% in advanced ESCC. Therefore, more effective therapeutic treatments were needed to prolong the survival urgently. Anlotinib was demonstrated to be an effective second-line monotherapy for patients with advanced or recurrent ESCC in China. And the preliminary results of our trial had been reported in 2020 ESMO (Abs 1448) and 2021 ASCO-GI Symposium (Abs 181). Consequently, this study was to investigate the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC and report the update results regularly. Methods: Pts with previously untreated metastatic or unresectable, locally advanced ESCC, who had not received (neo) adjuvant therapy/radical surgery within 6 months were recruited in this study. Eligible patients were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60̃75mg/m2, iv, d1̃3, q3w) plus anlotinib (10mg, po, d1̃14, q3w) for 4̃6 cycles as initial therapy. For those who did not have disease progression, maintenance treatment was treated with anlotinib monotherapy (10mg, po, d1̃14, q3w) until progression or unacceptable toxicity. The tumor response was assessed by investigator according to RECIST version 1.1 criteria using computed tomography scans every two cycles. The predefined sample size was 47. The primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Dec 2020, a total of 45 patients were enrolled. Among 34 pts who were available for efficacy and safety evaluation. there were 1 confirmed CR (2.9%), 26 confirmed PR (76.5%), 2 unconfirmed PR (5.9%) and 5 SD (14.7%). Consequently, ORR was 79.4% (95%CI: 62.1̃91.3) and DCR was 100.0% (95%CI: 89.7̃100.0). At the data cut-off date, 11 patients discontinued treatment due to PD, the preliminary prognostic result indicated that the median PFS of the 34 patients was 9.76 months (95%CI: 8.44-13.08). And the median OS was not yet available. Additionally, safety profile exhibited that the common drug-related adverse events were myelosuppression, gastrointestinal reaction, fatigue, hypertension, constipation, hypokalemia, hepatotoxicity and hemoptysis. And the common grade ≥3 adverse events were myelosuppression (20.6%), hypertension (8.8%), nausea and vomit (5.9%), fatigue (5.9%) and hypokalemia (5.9%). Conclusions: The update results suggested that the regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04063683.

PLATFORM: Planning treatment of oesophago-gastric (OG) cancer—A randomised maintenance therapy trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS187-TPS187 ◽  
Author(s):  
Catherine Cafferkey ◽  
Ian Chau ◽  
Fiona Thistlethwaite ◽  
Russell D. Petty ◽  
Naureen Starling ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
First Line ◽  
Her2 Positive ◽  
Open Label ◽  
Line Chemotherapy

TPS187 Background: Outcomes for patients with advanced OG cancer remain poor, median overall survival for fit patients treated with platinum and fluoropyrimidine based chemotherapy is less than one year, with second line chemotherapy resulting in a modest (approximately 6 weeks) survival benefit for selected patients. Evidence from NSCLC trials suggests a survival benefit from maintenance treatment following first line chemotherapy. Emerging data also supports the use of immunotherapy in previously treated OG cancer. The PLATFORM study aims to evaluate maintenance therapy in patients with advanced OG cancer. Methods: This is a prospective, open label, multicentre, randomised phase II clinical trial which will recruit at multiple UK cancer centres. Eligible patients are those who have measurable stable disease or better following completion of first line chemotherapy (at least 6 cycles) for locally advanced unresectable or metastatic disease. First line chemotherapy regime should contain a platinum and 5-fluoropyridimine (with trastuzumab if HER2 +), doublet or triplet drug combinations are permitted. Maintenance strategies are split by HER 2 status. For HER2 negative patients these are: Arm A1: surveillance, Arm A2: capecitabine, Arm A3: MEDI 4736 (anti PDL1 inhibitor) and for HER2 positive patients; Arm B1: trastuzumab, Arm B2: in development. Target recruitment is six hundred and sixteen patients, 154 patients will be recruited to each arm, with an interim analysis following recruitment of 61 patients to each arm. An adaptive trial design enables ineffective treatments to be discontinued early, with the opportunity to add novel treatment arms as the trial progresses. Primary endpoint is progression free survival. Secondary endpoints are progression free rate at 3, 6 & 12 months, overall survival, objective response rate by RECIST 1.1, toxicity and analysis of efficacy endpoints according to biomarker status for selected arms. Thirty two patients have been registered for the study with 3 patients randomised, recruitment is ongoing. Clinical trial information: EUDRACT: 2014-002169-30.

KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS185-TPS185 ◽  
Author(s):  
Josep Tabernero ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Atsushi Ohtsu ◽  
Uma Kher ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Phase Iii ◽  
Primary Study ◽  
First Line ◽  
Open Label ◽  
Double Blind ◽  
End Points ◽  
First Line Therapy ◽  
Line Therapy

TPS185 Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 designed to block its interaction with PD-L1 and PD-L2 and permit an antitumor immune response. In KEYNOTE-012, pembro showed a 22% ORR (RECIST v1.1, central review) and a manageable safety profile in patients (pts) with advanced gastric cancer. The randomized, phase 3 KEYNOTE-062 study (NCT02494583) is designed to compare the efficacy and safety of pembro alone or in combination with cisplatin + a fluoropyrimidine with those of cisplatin + a fluoropyrimidine as first-line therapy for PD-L1+/HER2– advanced gastric or GEJ adenocarcinoma. Methods: Key eligibility criteria include age ≥ 18 y, locally advanced or metastatic PD-L1+/HER2– gastric or GEJ adenocarcinoma, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for advanced disease. Pts are randomized 1:1:1 to pembro 200 mg Q3W (arm 1), pembro + cisplatin 80 mg/m2 Q3W + 5-fluorouracil (5-FU) 800 mg/m2 on days 1-5 of each Q3W cycle (arm 2), or placebo Q3W + cisplatin + 5-FU (arm 3); 5-FU may be replaced with capecitabine 1000 mg/m2 twice daily on days 1-14 of each cycle. Randomization is stratified by region (Europe/North America/Australia vs Asia vs rest of world), disease status (locally advanced vs metastatic), and chosen fluoropyrimidine (5-FU vs capecitabine). Arm 1 is open label; in arms 2 and 3, assignment to pembro vs placebo is double blind. In all arms, treatment will continue for 35 cycles or until progressive disease, unacceptable toxicity, or pt/investigator decision. Response will be evaluated every 6 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns; eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 3 mo. OS and PFS per RECIST v1.1 are the primary study end points; secondary end points include ORR and duration of response. Enrollment in KEYNOTE-062 is ongoing and will continue until ~750 pts have enrolled. Clinical trial information: NCT02494583.

Camrelizumab combined with capecitabine and oxaliplatin followed by camrelizumab and apatinib as first-line therapy for advanced or metastatic gastric or gastroesophageal junction cancer: Updated results from a multicenter, open label phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4031-4031 ◽  
Author(s):  
Lin Shen ◽  
Zhi Peng ◽  
Yan-Qiao Zhang ◽  
Jia Wei ◽  
Feng Wang ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy ◽  
Open Label Phase

4031 Background: Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for advanced or metastatic gastric cancer. Camrelizumab (SHR-1210, an anti–PD-1 antibody) shows promising anti-tumor activity in patients (pts) with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Camrelizumab combined with CAPOX for untreated G/GEJ cancer was assessed as a part of an ongoing multicenter, open-label phase 2 trial (cohort 1), and encouraging preliminary results were reported. Here, we present the updated safety and efficacy data. Methods: In this cohort, systemic treatment naïve pts with HER2– advanced or metastatic G/GEJ adenocarcinoma were given camrelizumab 200 mg on Day 1, capecitabine 1000 mg/m2 bid on Days 1–14 and oxaliplatin 130 mg/m2 on Day 1 of each 21-day-cycle for 4 to 6 cycles followed by camrelizumab 200 mg every 3 weeks plus apatinib 375 mg qd until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Results: At data cutoff (Jan 20, 2019), 43 of the 48 enrolled pts were evaluable. Partial response was observed in 28 pts (65%), and 19 (44%) were confirmed. Stable disease in 14 pts and progressive disease in 10 pts were reported. Median estimates for duration of response and progression-free survival were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 9 pts (21%), included neutropenia, diarrhea, rash and elevated ALT, whereas none of the TRAEs was fatal. Ten pts without progression after 4–6 cycles of camrelizumab and CAPOX combination therapy all received camrelizumab plus apatinib as sequential therapy, and no new safety signals were observed. Conclusions: The updated results confirmed that camrelizumab plus CAPOX followed by camrelizumab plus apatinib was well tolerated with noteworthy responses as first-line therapy in advanced or metastatic G/GEJ cancer pts. Expansion of this cohort in a phase 3 study are under way. Clinical trial information: NCT03472365.

Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16199-e16199
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Ming Lu ◽  
Xing Zhang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

Margetuximab (M) combined with anti-PD-1 (MGA012) or anti-PD-1/LAG-3 (MGD013) +/- chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS468-TPS468
Author(s):  
Daniel V.T. Catenacci ◽  
Minori Koshiji Rosales ◽  
Jon M. Wigginton ◽  
Hyun Cheol Chung ◽  
Harry H. Yoon ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy

TPS468 Background: Trastuzumab (T), a monoclonal antibody (mAb) targeting HER2, is standard of care palliative 1st-line therapy for advanced HER2+ GEJ/GC patients (pts). M, an Fc-engineered anti-HER2 mAb, targets the same HER2 epitope but with higher affinity for both 158V (high binding) and 158F (low binding) alleles of activating Fc receptor CD16A. M coordinately enhanced both innate and adaptive immunity, including antigen-specific T-cell responses to HER2. PD-1 and LAG-3 are T-cell checkpoint molecules that suppress T-cell function. MGA012 (INCMGA00012) is a humanized, hinge-stabilized, IgG4 κ anti-PD-1 mAb blocking binding of PD-L1 or PD-L2 to PD-1. MGD013 is a humanized Fc-bearing bispecific tetravalent protein that binds to both PD-1 and LAG-3, inhibiting their respective ligand binding. We previously reported that a CTX-free regimen of M+PD-1 blockade was well tolerated in GEJ/GC pts, and induced a 30% objective response rate (ORR). This was 2- to 3-fold greater than in historical controls with checkpoint inhibitors alone. This registration-directed trial assesses efficacy, safety, and tolerability of M+checkpoint inhibition ± CTX in metastatic/locally advanced, treatment-naïve, HER2+ GEJ/GC pts. Methods: This is a 2-cohort, adaptive open-label phase 2/3 study. The first single arm, CTX-free cohort A evaluates M+MGA012 in HER2+ (immunohistochemistry [IHC] 3+) and PD-L1+ (excluding microsatellite instability high) pts. After 40 pts are evaluated for response/safety, 60 more pts will be enrolled if the threshold for continuation is met. In randomized cohort B, HER2+ (IHC 3+ or 2+/fluorescent in situ hybridization+) pts are enrolled irrespective of PD-L1 status. Part 1 randomizes pts to 1 of 4 arms (50 pts each): control arm (T+CTX) or 1 experimental arm (M+CTX; M+CTX+MGA012; M+CTX+MGD013). CTX is investigator’s choice XELOX or mFOLFOX-6. Part 2 consists of control (T+CTX) vs 1 experimental arm (M+CTX) + either MGA012 or MGD013, depending on results from part 1; with 250 pts each. The primary efficacy endpoint for cohort A (both parts) is ORR per RECIST 1.1; for cohort B part 2 it is overall survival.

Randomized phase II study of weekly versus every-3-week ixabepilone plus bevacizumab (ixa/bev) versus paclitaxel plus bev (pac/bev) as first-line therapy for metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1029-1029
Author(s):  
H. S. Rugo ◽  
M. Campone ◽  
D. Amadori ◽  
A. Wardley ◽  
E. Villa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Human Tumor ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

1029 Background: Pac/bev is superior to pac alone as first-line therapy for MBC. Ixa/bev has greater preclinical activity than pac/bev in human tumor models. The primary objective of this trial was to evaluate objective response rates (ORR) of ixa/bev given weekly or every 3 weeks relative to pac/bev as 1st line therapy for women with advanced breast cancer. Methods: Women with measurable disease and no prior chemotherapy for advanced breast cancer (locally advanced or MBC) were randomized in a 3:3:2 ratio to Arm A (ixa 16 mg/m2 IV on days 1, 8 & 15 q28 days/ bev 10 mg/kg IV q 2 wks), Arm B (ixa 40 mg/m2 IV q3 wks / bev 15 mg/kg IV q 3 wks) or Arm C (pac 90 mg/m2 IV, schedule/bev as in Arm A). Treatment was continued until disease progression or unacceptable toxicity. Results: Key efficacy and safety results from a pre-planned analysis of all randomized subjects after at least 24 weeks of follow-up are presented. Baseline characteristics were balanced between arms except for liver metastasis. Conclusions: The combination of ixa/bev weekly or q 3 wks demonstrated encouraging clinical activity and safety comparable to 1st line pac/bev in E2100. Final PFS will be provided when data is mature. These results support ongoing clinical trials of ixa given weekly or q 3wk in 1st line MBC, and in combination with bev. [Table: see text] [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document