Development of a nomogram to predict overall survival in patients with locally advanced or metastatic gastrointestinal stromal tumor receiving first-line treatment with imatinib.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 10054-10054 ◽  
Author(s):  
D. Goldstein ◽  
C. Lee ◽  
Y. Hui ◽  
B. Shah ◽  
D. Yip ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gastrointestinal Stromal Tumor ◽  
Locally Advanced ◽  
Stromal Tumor ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Penpulimab in combination with anlotinib as first-line treatment in advanced nonsquamous non-small-cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21072-e21072
Author(s):  
Baohui Han ◽  
Jianhua Chen ◽  
Ziping Wang ◽  
Xingya Li ◽  
Lin WANG ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Drug Binding ◽  
Line Treatment ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Metastatic Nsclc ◽  
First Line Treatment

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.

Determinants of first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 468-468
Author(s):  
Hui-Li Wong ◽  
Ying Wang ◽  
Yaling Yin ◽  
Hagen F. Kennecke ◽  
Winson Y. Cheung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Locally Advanced ◽  
Treatment Selection ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
The Impact ◽  
First Line Treatment

468 Background: Chemotherapy options currently available for the first-line treatment of advanced PDAC include FOLFIRINOX (FX), gemcitabine with nab-paclitaxel (GP) and single agent gemcitabine (Gem). GP was introduced most recently and funded for clinical use in British Columbia (BC) in September 2014. In this retrospective analysis, we explore the impact of GP availability on first-line treatment selection and overall survival (OS) in advanced PDAC. Methods: The BC Cancer Agency provincial pharmacy database was used to identify patients (pts) who started FX, GP or Gem between January and August 2014 (pre-GP) or January and August 2015 (post-GP). Pts were eligible for inclusion if they received at least one cycle of first-line therapy for locally advanced or metastatic PDAC. Clinical data were extracted from electronic medical records. OS was defined as time from diagnosis of advanced PDAC to death and compared by treatment era, adjusting for age, ECOG, comorbidities, disease extent and baseline CA19-9. Results: 286 pts fulfilled eligibility criteria: 88 (31%) with locally advanced and 198 (69%) with metastatic disease. 131 and 155 pts were treated in the pre- and post-GP eras respectively. Prior to GP approval, 44% and 49% of pts received Gem and FX; this decreased to 21% and 33% after GP funding, with 46% of pts receiving GP in the latter period. Nine (7%) pts received GP in the pre-GP era, either through self-pay or addition of nab-paclitaxel after approval. There were no significant differences in pt characteristics across both eras. 46% of pts who received GP post approval had ECOG ≥ 2. The proportion of pts receiving second-line therapy was lower in the post-GP era (22% vs. 38%). Median OS in the post-GP era was 8.1 vs. 10.1 months in the pre-GP era; adjusted HR 1.28 (95% CI 0.96–1.71). Pts with ECOG ≥ 2 who received GP had a median OS of 6.5 months. Conclusions: After GP was funded, it became the preferred first-line regimen for advanced PDAC. Its more frequent use instead of FX did not appear to compromise overall survival even though a substantial proportion of pts were ECOG ≥ 2 and few pts received second-line therapy.

A phase I dose escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS453-TPS453
Author(s):  
Marcus Smith Noel ◽  
Philip Agop Philip ◽  
Mohamedtaki Abdulaziz Tejani ◽  
John Marshall ◽  
Aiwu Ruth He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

TPS453 Background: FOLFIRINOX remains the standard of care for the first line treatment of patients with locally advanced and metastatic pancreatic adenocarcinoma, however the prognosis remains poor, thus novel treatment options are indicated. 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. A randomized phase IIb study in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180) was previously conducted. 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. A second line pivotal randomized phase III trial (Trybeca-1) is currently enrolling (NCT03665441). We design this phase I study to determine the safety of mFOLFIRINOX combined with Eryaspase in the first line of treatment. Methods: Patients with locally or metastatic biopsy proven pancreatic adenocarcinoma will be treated with the combination of mFOLFIRINOX plus Eryaspase. This will be a standard 3+3 design with 4 possible doing levels. mFOLFIRINOX dosing will include 5-Fluorouracil 2400 mg/m2 over 46 hours, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 plus Eryaspase 75 Units/kg at dose level 0. Eryaspase will be dose escalated up to 100 Units/kg. The study will enroll at three academic centers. Key eligibility criteria include performance status 0 or 1; locally advanced or metastatic tumor disease; adequate organ function. The primary objective is to determine the maximum tolerated dose and safety of this novel combination. Key secondary objectives include objective response rate, progression-free survival, overall survival, pharmacokinetics, pharmacodynamics, and biomarker research. A data safety monitoring committee will review data every 3 months. Clinical trial information: 04292743.

Genomic biomarker discovery of first-line gemcitabine/nabpaclitaxel treatment in Chinese advanced pancreatic carcinoma patients.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 436-436
Author(s):  
Juan Du ◽  
Qiuyue Pan ◽  
Huizi Sha ◽  
Zhengyun Zou ◽  
Weiwei Kong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Amino Acid ◽  
Pancreatic Carcinoma ◽  
Locally Advanced ◽  
Single Amino Acid ◽  
Current Evidence ◽  
Amino Acid Substitutions ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

436 Background: Pancreatic carcinoma is one of the most lethal malignancies worldwide and is characterized by extremely poor prognosis. Gemcitabine plus Nab-paclitaxel (GNp) has been recommended by international guidelines for first-line treatment of locally advanced or metastatic pancreatic carcinoma. However, exploration into molecular biomarkers of GNp treatment is still limited. This study aims to observe and evaluate the efficacy and safety of first-line GNp treatment of pancreatic carcinoma, and to explore potential predictive and prognostic biomarkers to screen advantageous population. Methods: From December 20, 2018 to July 6, 2020, patients with metastatic pancreatic carcinoma, who received first-line GNp treatment, were enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AE). Patients were collected formalin fixed paraffin embedded (FFPE) samples and sequenced by a next-generation sequencing (NGS)-based 450 gene panel carried out by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: In this study, tissue samples from 101 patients were assessed by NGS, including 58 (57.4%) primary tissues and 43 (42.6%) metastasis tissues. So far, 72 patients were available for efficacy analysis, the ORR and DCR were 38.2% and 77.9%, respectively, and were similar between patients sampled from primary lesions and metastasis lesions. The PFS and OS were 176 days and 308 days, respectively. The most frequently mutated genes were KRAS (91.9%), TP53 (76.8%), CDKN2A (32.3%) and SMAD4 (26.3%). Germline pathogenic BRCA2 mutations were detected in 3 (3.0%) patients, while somatic mutations of BRCA2 were found in 2 (2.0%) patients. For KRAS, missense mutations resulted in single amino acid substitutions primarily at G12 (88.1%), and lower frequencies at Q61 (4.0%) and V14 (1.0%). At G12, five different amino acid substitutions have been identified, with G12D (37.6%) the predominant mutation, G12V (32.7%), G12R (11.9%), G12C (3.0%) and G12A (1.0%). The ORR to AG treatment was significantly higher in TP53-alteration (-alt, 47.1%) than in TP53-wild-type (-WT, 11.1%) subgroups (p=0.01). Median OS times in CDKN2B-alt and CDKN2B-WT patients were 180 days and 323 days (p=0.029), respectively. Conclusions: Current evidence indicates that GNp is a valuable option for the first-line treatment of metastatic pancreatic cancer. TP53 may serve as a novel response-predictive gene for GNp treatment in pancreatic carcinoma. Overall survival was significantly prolonged in CDKN2B-WT patients compared with CDKN2B-alt patients. This study provided insights in identifying patients who might potentially benefit from GNp therapy. Clinical trial information: NCT03768687.

scholarly journals Cetuximab: a standard approach to the first-line treatment of recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck

2011 ◽  
pp. 247-256
Author(s):  
Jacques Bernier
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
First Line Treatment

The burden of squamous cell carcinoma of the head and neck (SCCHN) on healthcare systems is expected to rise in line with projected increases in population sizes in general, and the relative proportion of elderly individuals in particular, underlining the need for effective, well tolerated treatment strategies. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab, is the only EGFR-targeted agent currently approved for use in the treatment of SCCHN. Adding cetuximab to standard first-line platinum-based chemotherapy in the treatment of recurrent and/or metastatic SCCHN significantly improved overall survival (hazard ratio [HR] 0.80; P = 0.04), progression-free survival (HR 0.54; P\0.001) and response rates (odds ratio 2.33; P\0.001), compared to platinum-based chemotherapy alone. This was the first time in 30 years that a significant increase in overall survival had been achieved over platinum- based therapy alone and established cetuximab plus platinum-based chemotherapy as the new standard first-line treatment approach for recurrent and/or metastatic disease. In locally advanced SCCHN, cetuximab plus radiotherapy significantly improved locoregional control (HR 0.68, P = 0.005) and overall survival (HR 0.74; P = 0.03) compared to radiotherapy alone. In both recurrent and/or metastatic disease and locally advanced disease, adding cetuximab to standard therapy was generally well tolerated and did not affect patients’ quality of life. The clinical benefits seen with the addition of cetuximab to standard chemotherapy or radiotherapy make it one of the most significant advances made in SCCHN treatment in recent years.

scholarly journals Cetuximab: a standard approach to the first-line treatment of recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck

2011 ◽  
Vol 3 (4) ◽  
pp. 247
Author(s):  
Jacques Bernier
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
First Line Treatment

The burden of squamous cell carcinoma of the head and neck (SCCHN) on healthcare systems is expected to rise in line with projected increases in population sizes in general, and the relative proportion of elderly individuals in particular, underlining the need for effective, well tolerated treatment strategies. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab, is the only EGFR-targeted agent currently approved for use in the treatment of SCCHN. Adding cetuximab to standard first-line platinum-based chemotherapy in the treatment of recurrent and/or metastatic SCCHN significantly improved overall survival (hazard ratio [HR] 0.80; P = 0.04), progression-free survival (HR 0.54; P\0.001) and response rates (odds ratio 2.33; P\0.001), compared to platinum-based chemotherapy alone. This was the first time in 30 years that a significant increase in overall survival had been achieved over platinum- based therapy alone and established cetuximab plus platinum-based chemotherapy as the new standard first-line treatment approach for recurrent and/or metastatic disease. In locally advanced SCCHN, cetuximab plus radiotherapy significantly improved locoregional control (HR 0.68, P = 0.005) and overall survival (HR 0.74; P = 0.03) compared to radiotherapy alone. In both recurrent and/or metastatic disease and locally advanced disease, adding cetuximab to standard therapy was generally well tolerated and did not affect patients’ quality of life. The clinical benefits seen with the addition of cetuximab to standard chemotherapy or radiotherapy make it one of the most significant advances made in SCCHN treatment in recent years.

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