scholarly journals AGIG Chemo-Immunotherapy in Patients With Advanced Pancreatic Cancer: A Single-Arm, Single-Center, Phase 2 Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Wangshu Dai ◽  
Xin Qiu ◽  
Changchang Lu ◽  
Zhengyun Zou ◽  
Huizi Sha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Option ◽  
Performance Status ◽  
Interleukin 2 ◽  
Advanced Pancreatic Cancer ◽  
Common Adverse Event ◽  
Efficacy And Safety ◽  
First Line ◽  
Clinical Trial Registration ◽  
Gm Csf

BackgroundTo date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the past few years, the interest in immunological anticancer therapy rises sharply. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen.MethodsNab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 (1000000U) and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions along with the efficacy and safety were assessed every two cycles.ResultsBetween 11/2018 and 01/2020, sixty-four patients were enrolled. In the sixty-four evaluable patients, the disease control rate (DCR) and overall response rate (ORR) were 76.6% and 43.75%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months. The median PFS was 5.7 (range 1.63–15.8) months. The median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of III/IV grade neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival.ConclusionsThe AGIG chemo-immunotherapy regimen has presented favorable ORR, OS, and manageable toxicities as first-line therapeutic strategy of advanced pancreatic cancer treatment. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response.Clinical Trial Registrationhttps://clinicaltrials.gov/. identifier NCT03768687.

AGIG chemo-immunotherapy in patients with advanced pancreatic cancer: A single-arm, single-center, phase II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 384-384
Author(s):  
Wangshu Dai ◽  
Xin Qiu ◽  
Changchang Lu ◽  
Zhengyun Zou ◽  
Huizi Sha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Therapeutic Option ◽  
Performance Status ◽  
Interleukin 2 ◽  
Advanced Pancreatic Cancer ◽  
Efficacy And Safety ◽  
First Line ◽  
Gm Csf

384 Background: To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the last few years, the interest in the use of immunological anticancer strategies is greatly increased. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen. Methods: Nab-paclitaxel (120 mg/m2) and gemcitabine (1000 mg/m2) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: Between 11/2018 and 01/2020, 64 patients were enrolled. In the 64 evaluable patients, the ORR and DCR were 43.75% and 76.6%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months, the median PFS was 5.7 (range 1.63–15.8) months, and the median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of grade 3/4 neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival. Conclusions: The AGIG Chemo-immunotherapy regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response. Clinical trial information: NCT0376867. Research Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School. [Table: see text]

PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4665-TPS4665
Author(s):  
Jiujie Cui ◽  
Jiayu Yao ◽  
Yu Wang ◽  
Yiyi Liang ◽  
Yongchao Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Tumor Therapy ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .

Efficacy and safety of nab-paclitaxel plus s-1 in the first-line treatment of advanced pancreatic cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16217-e16217
Author(s):  
Wen Zhang ◽  
Chun-Xia Du ◽  
Yongkun Sun ◽  
Lin Yang ◽  
Chengxu Cui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

scholarly journals Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1746 ◽  
Author(s):  
Kun-I Lin ◽  
Jia-Lian Yang ◽  
Yu-Chao Lin ◽  
Che-Yi Chou ◽  
Jin-Hua Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Current Evidence ◽  
P Value ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

scholarly journals Efficacy and Safety of Gemcitabine as First-Line Therapy in Patients Aged 65 and Older with Advanced Pancreatic Cancer

2014 ◽  
Vol 25 ◽  
pp. v73
Author(s):  
Yosuke Kito ◽  
Akiko Todaka ◽  
Akira Fukutomi ◽  
Kenji Kunieda ◽  
Takahiro Tsushima ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

First-line drug selection versus sequential treatment in advanced pancreatic cancer: Does it really matter? Multi-institutional Canadian perspective.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 673-673
Author(s):  
Ivan Barrera ◽  
Neha Papneja ◽  
Jill Ranger ◽  
Abhishek Papneja ◽  
Petr Novotny ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Performance ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
First Line ◽  
Log Rank Test ◽  
Canadian Perspective ◽  
Grade 3 ◽  
Line Drug

673 Background: Folfirinox (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine (G) in the first line treatment (1LTx) for advanced pancreatic cancer (APC). Yet, the optimal 1LTx selection nor sequential Tx (ST) has not been fully established. Therefore, the best choice for 1LTx is a matter of debate often influenced by access to drugs. This analysis was conducted to compare outcomes based on 1Ltx selection and ST in APC. Methods: We assessed patients (pts) with APC who received either FFX or GN as 1LTx during 2010-2019 at three Canadian institutions. As well as the ST used. The main objective was to assess survival. Kaplan method and log-rank test were used for survival curves. Results: This retrospective study included 231 pts; 1LTx included 143 pts on FFX and 88 pts on GN. FFX pts were predominantly male; 89(62.2%) vs 46(52.3%) and slightly younger (median age 62 vs 66) than GN. WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. There were more grade 3-4 toxicity in FFX vs GN group: GI 55 (38.5%) vs 15 (17%) and hematologic 51 (35.4%) vs 20 (22.7%) respectively. Grade 3-4 neutropenia rates were similar in both regimens. The median PFS of FFX was 5.5 months (95% CI: 5.0-6.7) vs 5.1 (95% CI: 3.8-7.1) with GN (p=0.37). The median OS with FFX was 9.3 months (95% CI: 7.5-11.1) vs 10.2 (95% CI: 6.8-11.3) with GN (p=0.81). There were not statically significant. Table shows Tx frequency across 4LTx. 2LTx and beyond regimens included G, GN, FFX, Capecitabine, Irinotecan liposome plus 5-FU, Irinotecan and clinical trials. Conclusions: Our results revealed that pts who received 1LTx FFX or GN had similar PFS and OS even though 1LTx FFX group was younger with better PS, allowing to continue 2-4LTx more frequently when compare with 1LTx GN group. Therefore, 1LTx selection appear to have more impact in our pts rather than ST, whereas GN is less toxic and seems a preferable 1LTx choice for most pts. FFX could be reserved for young high-performance pts. [Table: see text]

Investigating real-world treatment sequencing outcomes in advanced pancreatic cancer: A purple translational registry analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 386-386 ◽  
Author(s):  
Jordan Santucci ◽  
Belinda Lee ◽  
Shehara Ramyalini Mendis ◽  
Benjamin N Thomson ◽  
Michael Michael ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
De Novo ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Survival Outcomes ◽  
First Line ◽  
Treatment Sequencing

386 Background: Current standard combination first line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head trials. Data on optimum treatment sequencing is also lacking. Methods: To assess whether first line (1L) treatment with gemcitabine/nab-paclitaxel (Gem/Nab-P)(SEQ1) or FOLFIRINOX (SEQ2) in the palliative treatment setting impacts survival outcomes, data for patients receiving palliative intent combination chemotherapy between 2016 and May 2020 was extracted from PURPLE, a prospective pancreatic cancer registry enrolling consecutive patients across multiple institutions. Results: Of 637 patients, 180 (28%) who received 1L single agent therapy and/or palliative radiotherapy were excluded. Of the remaining 449 patients, 132 (29%) had locally advanced disease (LA PDAC), 67 had local recurrence (15%), and 250 (56%) had de novo metastatic disease (mPDAC). Patients receiving 1L Gem/Nab-P (n=376, 84%) were older (median 67 vs 59 years, P<0.001), had a higher Charlson Comorbidity Index (CCI) (CCI ≥2: 18% vs 3%, Odds Ratio [OR] 8.0, P=0.002), and poorer performance status (ECOG≥2: 10% vs 1%, OR 8.4, P=0.01) compared to the 1L FOLFIRINOX group (n=73, 16%). 140 (37%) patients receiving 1L Gem/Nab-P (SEQ1) and 32 (44%) patients receiving 1L FOLFIRINOX (SEQ2) received second line (2L) chemotherapy. SEQ1 2L regimens included FOLFIRINOX (n=14), FOLFIRI (n=49), FOLFOX (n=35) and 5FU alone (n=3). SEQ2 2L regimens included Gem/Nab-P (n=19), Gem/5FU (n=4), Gem/Cisplatin (n=1) and gemcitabine alone (n=5). Median progression free survival (mPFS) did not differ between patients receiving 1L Gem/Nab-P vs 1L FOLFIRINOX (5.7 vs 5.1 months, P=0.54); nor did median overall survival (mOS; 11.3 vs 12.3 months, P=0.37). In the subset of patients who went on to receive 2L chemotherapy, mPFS in 2L was shorter for SEQ1 compared to SEQ2 (2.9 vs 5.2 months, Hazard Ratio [HR] 1.3, P=0.03) but mOS did not differ (15.9 vs 17.3 months P=0.91). In the subset with LA PDAC, mPFS in 2L was comparable (2.9 vs 3.3 months, P=0.55) but mOS was significantly longer with SEQ1 (22.5 vs 13.8 months, HR 0.50, P=0.01). In mPDAC, mPFS in 2L was shorter with SEQ1 (2.3 vs 5.6 months, HR 1.64, P=0.03), but mOS did not differ by sequence (13 vs 17 months, P=0.23). Conclusions: There were no significant differences in survival outcomes between 1L choices of chemotherapy, despite patients offered 1L FOLFIRINOX (SEQ2) being younger and fitter. Survival differences observed for LA PDAC versus mPDAC will be further explored. Given the multiple potential confounders, randomised clinical trials are needed to make firmer conclusions regarding the optimal initial treatment for each patient subset.

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