scholarly journals A Peptide-Based Neoantigen Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment

2020 ◽  
Author(s):  
Zheling Chen ◽  
Shanshan Zhang ◽  
Ning Han ◽  
Jiahong Jiang ◽  
Yunyun Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Clinical Efficacy ◽  
Peripheral Blood ◽  
Cancer Vaccines ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Vaccine Treatment ◽  
Potential Biomarker ◽  
New Strategy

Abstract Background: Tumor-specific neoantigens are considered as personalized and potential ultimate targets for cancer immunotherapy. Recently, neoantigen cancer vaccines have been designed to train the patient's immune system to specifically target and kill tumor cells. However, the safety and efficacy of neoantigen vaccines in pancreatic cancer treatment remain poorly understood. Methods: Personalized peptide neoantigen cancer vaccines were successfully designed and manufactured for pancreatic cancers with low tumor mutation burden. Seven patients with advanced pancreatic cancer refractory to standard treatments were enrolled and treated with personalized peptide neoantigen vaccine, iNeo-Vac-P01. Besides the evaluation of the safety and clinical efficacy of iNeo-Vac- P01, pre- and post-vaccination peripheral blood samples were collected to analyze the vaccine’s immunogenicity.Results: For all 7 patients, none sever vaccine-related adverse effects was witnessed. The mean progression free survival, overall survival (OS) and OS associated with vaccine treatment were 3.1, 24.1 and 8.3 months, respectively. For Patient P01, who had a 21-month OS associated with vaccine treatment, the abundance of the TCR clone remarkably increased after vaccination, indicating the potential of iNeo-Vac-P01 to specifically induce a subset of T cells to kill tumor cells. This study also demonstrated that the quantity of IFN-γ in peripheral blood might be a potential biomarker for OS.Conclusions: We believed that it was the first tentative study focused in the application of peptide-based neoantigen cancer vaccine in advanced pancreatic cancer. Promisingly, personalized peptide neoantigen vaccine might provide a new strategy to improve the limited clinical efficacy for pancreatic cancer.Trial registration: ClinicalTrials.gov, NCT03645148. Registered August 24, 2018 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03645148?term=neoantigen&cond=Pancreatic+Cancer&cntry=CN&draw=2&rank=1

scholarly journals A peptide-based neoantigen vaccine for patients with advanced pancreatic cancer refractory to standard treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14563-e14563
Author(s):  
Liu Yang ◽  
Shuqing Chen ◽  
Fan Mo ◽  
Zheling Chen ◽  
Jiahong Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Clinical Efficacy ◽  
Peripheral Blood ◽  
Cancer Vaccines ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Vaccine Treatment ◽  
Potential Biomarker ◽  
New Strategy

e14563 Background: Tumor-specific neoantigens are considered as personalized and potential ultimate targets for cancer immunotherapy. Recently, neoantigen cancer vaccines have been designed to train the patient's immune system to specifically target and kill tumor cells. However, the safety and efficacy of neoantigen vaccines in pancreatic cancer treatment remain poorly understood. Methods: Personalized peptide neoantigen cancer vaccines were successfully designed and manufactured for pancreatic cancers with low tumor mutation burden. Seven patients with advanced pancreatic cancer refractory to standard treatments were enrolled and treated with personalized peptide neoantigen vaccine, iNeo-Vac-P01. Besides the evaluation of the safety and clinical efficacy of iNeo-Vac- P01, pre- and post-vaccination peripheral blood samples were collected to analyze the vaccine’s immunogenicity. Results: For all 7 patients, none sever vaccine-related adverse effects was witnessed. The mean progression free survival, overall survival (OS) and OS associated with vaccine treatment were 3.1, 24.1 and 8.3 months, respectively. For Patient P01, who had a 21-month OS associated with vaccine treatment, the abundance of the TCR clone remarkably increased after vaccination, indicating the potential of iNeo-Vac-P01 to specifically induce a subset of T cells to kill tumor cells. This study also demonstrated that the quantity of IFN-γ in peripheral blood might be a potential biomarker for OS. Conclusions: We believed that it was the first tentative study focused in the application of peptide-based neoantigen cancer vaccine in advanced pancreatic cancer. Promisingly, personalized peptide neoantigen vaccine might provide a new strategy to improve the limited clinical efficacy for pancreatic cancer. Clinical trial information: NCT03645148.

scholarly journals EVALUATING MMP-2 AND TGFß-RI EXPRESSION IN CIRCULATING TUMOR CELLS OF PANCREATIC CANCER PATIENTS AND THEIR CORRELATION WITH CLINICAL EVOLUTION

2019 ◽  
Vol 32 (2) ◽  
Author(s):  
José Luiz GASPARINI-JUNIOR ◽  
Marcello Ferretti FANELLI ◽  
Emne Ali ABDALLAH ◽  
Ludmilla Thomé Domingos CHINEN
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Clinical Characteristics ◽  
Epithelial Mesenchymal Transition ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Clinical Findings ◽  
Mesenchymal Transition

ABSTRACT Background: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. Aim: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). Method: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. Results: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. Conclusion: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.

scholarly journals Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

2020 ◽  
Vol 12 ◽  
pp. 175883592097715
Author(s):  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
Tingshi Su ◽  
Xixu Zhu ◽  
Xiaoping Ju ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Multicenter Cohort Study ◽  
Failure Patterns ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Contrast Ct

Objective: This study aims to compare recurrence patterns and outcomes of biologically effective dose (BED10, α/β = 10) of 60–70 Gy with those of a BED10 >70 Gy for locally advanced pancreatic cancer (LAPC). Methods: Patients from three centers with a biopsy and a radiographically proven LAPC were retrospectively included and data were prospectively collected from June 2012 to June 2019. Radiotherapy was delivered by stereotactic body radiation therapy. Recurrences were categorized as in-field, marginal, and outside-the-field recurrence. Patients in two groups were required to receive abdominal enhanced contrast CT or MRI every 2–3 months and CA19-9 examinations every month during follow-up. Treatment-related toxicities were evaluated every month. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: After propensity score matching, there were 486 patients in each group. The median prescription dose of the two groups was 37 Gy/5–8 f (range: 36–40.8 Gy/5–8 f) and 42 Gy/5–8 f (range: 40–49.6 Gy/5–8 f), respectively. The median OS of patients with a BED10 >70 Gy and a BED10 60–70 Gy was 20.3 months (95% CI: 19.1–21.5 months) and 18.2 months (95% CI: 17.8–18.6 months) respectively ( p < 0.001). The median PFS of the two cohorts was 15.4 months (95% CI: 14.2–16.6 months) and 13.3 months (95% CI: 12.9–13.7 months) respectively ( p < 0.001). A higher incidence of in-field and marginal recurrence was found in patients with BED10 of 60–70 Gy (in-field: 97/486 versus 72/486, p = 0.034; marginal: 109/486 versus 84/486, p = 0.044). However, more patients with BED10 >70 Gy had grade 2 or 3 acute (87/486 versus 64/486, p = 0.042) and late gastrointestinal toxicities (77/486 versus 55/486, p = 0.039) than those with BED10 of 60–70 Gy. Conclusion: BED10 >70 Gy was found to have the best survival benefits along with a higher incidence of acute and late gastrointestinal toxicities. Therefore, a higher dose may be required in the case of patients’ good tolerance.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

scholarly journals Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review

2019 ◽  
Vol 11 ◽  
pp. 175883591985036 ◽  
Author(s):  
Elena Gabriela Chiorean ◽  
Winson Y. Cheung ◽  
Guido Giordano ◽  
George Kim ◽  
Salah-Eddin Al-Batran
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Real World ◽  
Controlled Trial ◽  
Safety Data ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Grade 3

Background: No clinical trial has directly compared nab-paclitaxel/gemcitabine (nab-P/G) with FOLFIRINOX (fluorouracil/leucovorin/oxaliplatin/irinotecan) in metastatic or advanced pancreatic cancer (mPC or aPC). We conducted a systematic review of real-world studies comparing these regimens in the first-line setting. Methods: Embase and MEDLINE databases through 22 January 2019, and Gastrointestinal Cancers Symposium 2019 abstracts were searched for real-world, retrospective studies comparing first-line nab-P/G versus FOLFIRINOX in mPC or aPC that met specific parameters. Studies with radiotherapy were excluded. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Of 818 records initially identified, 35 were duplicates and 749 did not meet the eligibility criteria, mostly because they were either not comparative ( n = 356) or not first line ( n = 245). The remaining 34 studies (21 mPC; 13 aPC) assessed >6915 patients who received nab-P/G or FOLFIRINOX. In the studies identified, the median overall survival (OS) reached 14.4 and 15.9 months with nab-P/G and FOLFIRINOX, respectively, and median progression-free survival reached 8.5 and 11.7 months, respectively. Safety data were reported in 14 studies (2205 patients), including 8 single-institutional studies. In most single-institutional studies that reported safety data, rates were higher with FOLFIRINOX versus nab-P/G for grade 3/4 neutropenia (five of six studies) and febrile neutropenia (all three studies), while rates of grade 3/4 peripheral neuropathy were higher with nab-P/G in four of seven studies. Conclusions: Although FOLFIRINOX was associated with slightly longer median OS in more studies, the differences, when available, were not statistically significant. Therefore, a randomized, controlled trial is warranted. Toxicity profile differences represent key considerations for treatment decisions.

scholarly journals Analysis of clinical efficacy of CyberKnife® treatment for locally advanced pancreatic cancer

2015 ◽  
pp. 1427 ◽  
Author(s):  
Yongchun Song ◽  
Zhiyong Yuan ◽  
Fengtong Li ◽  
Yang Dong ◽  
Hongqing Zhuang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Efficacy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Efficacy and safety of 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) for previously treated advanced pancreatic cancer (APC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 407-407
Author(s):  
Hiromichi Shirasu ◽  
Takeshi Kawakami ◽  
Satoshi Hamauchi ◽  
Takahiro Tsushima ◽  
Akiko Todaka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Cycle ◽  
Initial Dosage ◽  
Advanced Pancreatic Cancer ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Line Treatment ◽  
Median Treatment ◽  
Treatment Line

407 Background: 5-fluorouracil (5-FU) / levofolinate / irinotecan (FOLFIRI) is one of the preferred regimens for patients (pts) with advanced pancreatic cancer (APC) who received prior gemcitabine-based therapy in the National Comprehensive Cancer Network Guidelines. However, its survival benefit or safety in clinical practice is unclear. Methods: We retrospectively assessed the data of consecutive pts with APC who received FOLFIRI as a second or later-line treatment after gemcitabine-based therapy at Shizuoka Cancer Center between May 2014 and March 2020. Results: The characteristics of 102 pts included in this analysis were as follows: median age (range), 67 (39-78) y; male/female, 55/47; ECOG PS0/1/2, 21/72/9; the number of metastatic sites 0/1/2/3/4, 7/48/35/8/4; unresectable/recurrent, 84/18; UGT1A1 status wild/*6 or*28 heterozygous/homo or double-heterozygous/unknown, 40/40/5/17; treatment line of FOLFIRI 2nd/3rd/4th, 64/32/6. Previous treatment history according to the treatment line of FOLFIRI was as follows: 2nd-line, all patients received GEM-based regimen, GEM plus nanoparticle albumin bound paclitaxel in 63 pts (98.4%) and GEM in 1 (1.6%); 3rd, GEM-based and S1 in 20 (62.5%), GEM-based and 5-FU/levofolinate/oxaliplatin (FOLFOX) in 12 (37.5%); 4th, GEM-based, FOLFOX and S-1 or other agent in 5 (83.3%), 2 GEM-based regimens and S1 in 1 (16.7%). The median treatment cycle was 5 (range 1-55). The median treatment cycle according to the treatment line was as follows: 2nd-line, 7(1-55); 3rd, 4(1-14); 4th, 3.5(1-10). The initial dosage for each cytotoxic agent was as follows: bolus 5-FU injected/omited 72/30; continuous 5-FU 2400/2000/1200 mg/m2, 88/13/1; irinotecan 180/150/120/less than or equal to 100mg/m2, 27/59/13/3. The overall response rate (ORR) and disease control rate (DCR) were 5.9% and 52.9%, respectively. ORR and DCR according to the treatment line were as follows: 2nd-line, 9.3/64.1%; 3rd, 0/68.8%; 4th, 0/50.0%. At the median follow up 6.5 M, the median overall survival (OS) and progression free survival (PFS) were 6.6M and 3.1M, respectively. The median OS and PFS according to the treatment line were as follows: 2nd-line, 8.1/3.6M; 3rd, 5.1/2.1M; 4th, 6.6/2.0M. Adverse events (AEs) were observed in 70.8% pts. Grade 3 or higher AEs occurred in 27.2% pts [neutropenia in 26 (25.2%) pts, febrile neutropenia in 4 (3.9%) pts, nausea in 4 (3.9%) pts, decreased appetite in 3 (2.9%) pts]. No treatment related deaths were observed. Conclusions: FOLFIRI is well tolerated and effective especially in the second-line treatment for pts with gemcitabine-refractory APC.

scholarly journals Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Dose Reductions

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

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