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

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.

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

Chemotherapy ◽

10.1159/000517244 ◽

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

Introduction: 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. Methods: 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. Results: 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%). Conclusions: GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

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Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.413 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 413-413 ◽

Cited By ~ 2

Author(s):

Sofia Palacio ◽

Ikechukwu Immanuel Akunyili ◽

Vinicius Ernani ◽

Jessica Macintyre ◽

Jaime R. Merchan ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Benefit ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Second Line ◽

Positive Interaction ◽

Line Therapy ◽

Third Line

413 Background: The combination of nab-P and Gem improves survival compared to Gem alone in first-line therapy of metastatic pancreatic cancer. Efficacy data with this doublet in previously treated pts are scant. Our group presented preliminary results on 10 pts treated with this two-drug combination in the second and third line setting and herein present updated data on 59 pts. Methods: This IRB approved analysis identified all pts diagnosed with advanced refractory pancreatic cancer, treated with second-line Gem and nab-P at University of Miami and Sylvester Comprehensive Cancer Center between September 2010 and June 2014. Response by RECIST, CA19-9, and symptomatic improvement were assessed. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of Gem + nab-P and were analyzed using the Kaplan-Meier method. Clinical benefit was defined as the percentage of patients with a partial response (PR) or stable disease (SD). Results: Data from59 pts were analyzed. The median age was 60; 55% were male; 54% received Gem + nab-P as second line therapy and 46% received it as third-line or beyond. Five (10%) pts had confirmed PR, 23 (47%) SD and 21 (43%) progressed. Among the 31 (52%) pts who received prior Gem, 18 (58%) had clinical benefit, 3 PR and 15 SD. The median OS was 3.9 months. The median PFS was 3 months. Toxicity appears similar to what has been reported on the MPACT trial with the combination. Conclusions: The clinical benefit seen withGem and nab-P in this group of pretreated pancreatic cancer pts suggests that it can be considered as an option. Additionally, prior Gem treatment appears not to decrease Gem and nab-P benefit in this population. Since nab-P monotherapy has modest activity in pre-treated pancreatic cancer pts, our data suggests a positive interaction between Gem and nab-P that may overcome resistance to Gem. [Table: see text]

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Risk factors of chemotherapy-induced nausea and vomiting in patients with advanced pancreatic cancer receiving modified FOLFIRINOX.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.344 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 344-344

Author(s):

Akira Shinohara ◽

Masafumi Ikeda ◽

Ai Irisawa ◽

Misaki Kobayashi ◽

Ryoko Udagawa ◽

...

Keyword(s):

Risk Factors ◽

Pancreatic Cancer ◽

Adverse Events ◽

Treatment Cycle ◽

Advanced Pancreatic Cancer ◽

Incidence Rates ◽

Nausea And Vomiting ◽

Cancer Center ◽

Younger Age ◽

Delayed Cinv

344 Background: Modified FOLFIRINOX (mFFX) has been reported to be a high incidence of chemotherapy-induced nausea and vomiting (CINV). However, CINV is difficult to adequately control in patients receiving treatment with mFFX. The aim of this study is to evaluate the incidence of delayed CINV and to identify as risk factors for CINV in patients receiving treatment with mFFX. Methods: The study subjects were patients with advanced pancreatic cancer treated with mFFX from December 2013 to June 2015 at National Cancer Center Hospital East. The mFFX regimen consisted of oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, l-leucovorin 200 mg/m2 and a 46-h continuous infusion of fluorouracil 2400 mg/m2. The antiemetic prophylaxis consisted of aprepitant (125 mg on day1 and 80 mg on day 2-3), palonosetron (0.75 mg on day1) and dexamethasone (12 mg on day1 and 8 mg on day 2-3). All adverse events, including nausea and vomiting were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE version 4.0). Results: A total of 115 patients were enrolled in this study. The incidence rates of nausea and vomiting of any grade during the first treatment cycle were 45.2% and 5.2%, respectively. Grade 2-3 of nausea and vomiting were observed in 13.9% and 0.9% of the patients, respectively. Any grade of CINV occurred frequently during days 4 to 7 for the first treatment cycle. Univariate and multivariate analyses identified female and younger age ( < 50 years) as significant independent factors associated with the incidence of any grade of CINV on days 4 to 7 for the first treatment cycle (Odds ratio [OR], 7.44; 95%CI, 2.21 to 25.1; p = 0.001; OR, 4.57; 95% CI, 1.04 to 20.1; p = 0.044). Conclusions: The risk factors of delayed CINV for the first treatment cycle were identified as female and younger age in patients treated with mFFX. Therefore, in patients with these risk factors, additional dexamethasone should be considered as an antiemetic treatment on day 4-5.

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Retrospective comparison of modified FOLFIRINOX with full-dose FOLFIRINOX for advanced pancreatic cancer: A Japanese cancer center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.469 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 469-469 ◽

Cited By ~ 1

Author(s):

Akihiro Ohba ◽

Hideki Ueno ◽

Yasunari Sakamoto ◽

Shunsuke Kondo ◽

Chigusa Morizane ◽

...

Keyword(s):

Pancreatic Cancer ◽

Dose Reduction ◽

Advanced Pancreatic Cancer ◽

Group Versus ◽

Progression Free Survival ◽

Cancer Center ◽

Control Group ◽

Phase 2 ◽

Full Dose ◽

Grade 3

469 Background: Various modified FOLFIRINOX (mFFX) regimens have been reported and widely used in clinical practice. Although there are retrospective studies and single-arm phase 2 studies comparing modified regimens to the full-dose regimen of the historical control group, head-to-head comparisons in the same population are limited. This study aimed to compare mFFX with full-dose FOLFIRINOX (fFFX) in patients with advanced pancreatic cancer (APC). Methods: We reviewed 85 patients with APC who received mFFX (no bolus fluorouracil and irinotecan 150 mg per square) or fFFX as first-line chemotherapy between January 2014 and December 2016. mFFX has been used since January 2016 on the basis of results of a Japanese phase 2 study. The efficacy, safety, and dose reduction pattern were evaluated. Results: A total of 56 eligible patients (26 treated with mFFX and 30 with fFFX) were selected. Baseline characteristics of each group were well-balanced. The median relative dose intensities of oxaliplatin, irinotecan, bolus fluorouracil, and continuous infusion fluorouracil were 68.6%, 78.5%, 0%, and 88.5% in the mFFX group, and 80.5%, 76.5%, 25.6%, and 83.6% in the fFFX group, respectively. Second cycle dose reduction occurred in 38% of the patients in the mFFX group and in 62% of those in the fFFX group. The median overall survival (OS) was 19.0 months in the mFFX group, compared to 13.2 months in the fFFX group (HR 0.60, 95% CI 0.25–1.47, P = 0.27). In a multivariate analysis to adjust for prognostic factors for OS, the hazard ratio for death with mFFX was significant (adjusted HR 0.36, 95% CI 0.14–0.93, P = 0.04). The median progression-free survival was 8.3 months in the mFFX group and 5.9 months in the fFFX group (HR 0.83, 95% CI 0.44–1.54, P = 0.55). The response rate was 35% in the mFFX group versus 30% (P = 0.78) in the fFFX group, respectively. Grade 3 or 4 leucopenia (15% versus 40%), neutropenia (42% versus 70%), febrile neutropenia (8% versus 17%), and nausea (4% versus 13%) were decreased in the mFFX group, but the differences were not statistically significant. Conclusions: mFFX had equivalent or higher efficacy and improved safety compared to fFFX in the same population.

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Is gemcitabine effective for pancreatic cancer after progression to FOLFIRINOX?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.489 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 489-489

Author(s):

Bruno Melo Fernandes ◽

Rafael Caparica Bitton ◽

Jorge Sabbaga ◽

Paulo Marcelo Hoff

Keyword(s):

Pancreatic Cancer ◽

Disease Progression ◽

Advanced Pancreatic Cancer ◽

Significant Risk ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Line Chemotherapy ◽

First Line Treatment

489 Background: Cytotoxic chemotherapy with FOLFIRINOX (5-Fluoracil + Irinotecan + Oxaliplatin) is considered the standard treatment for fit patients (pts) with pancreatic adenocarcinoma. Disease progression after FOLFIRINOX invariably occurs, and there is no definition on the optimal strategy for the second-line treatment of these pts. Gemcitabine is effective for advanced pancreatic cancer as first-line treatment, but its role after FOLFIRINROX progression is unknown. The present study aims to assess the efficacy of gemcitabine for treatment of advanced pancreatic cancer after progression to FOLFIRINOX. Methods: Single-institution, retrospective analysis of all pts consecutively diagnosed with advanced pancreatic cancer between January/2010, and October/2015, who received Gemcitabine as second line chemotherapy after progression to first line chemotherapy with FOLFIRINOX. Tumor responses were assessed through RECIST 1.1. PFS and OS were calculated using Kaplan Meier method. Results: 28 pts were included in our analysis. Median age was 55 years (38-75), and 19 pts (67%) were male. The median ECOG was 1 (0-2). Pts received a median of 9 cycles of FOLFIRINOX as first line treatment (1-27), with an objective (ORR) response rate of 39%. The median number of second-line Gemcitabine cycles was 3 (1-8), with an ORR of 3%, and a 17% rate of disease control (stable disease + partial response). Five patients (18%) discontinued second line Gemcitabine due to toxicities and the remaining 23 (82%) due to disease progression. Median overall survival was 5.6 months (0,36-11,5) and median progression-free survival was 2 months (0.2-7.7). Grade ≥ 3 toxicities with Gemcitabine were experienced by 18% of the patients. No treatment-related deaths were reported. Conclusions: Gemcitabine after progression to FOLFIRINOX presented a modest activity on the present study, with prospective trials being necessary to further assess this issue. Due to the palliative goal of the treatment, with the objective of improving patient´s quality of life, the significant risk of treatment-related adverse events and the low efficacy of Gemcitabine should be considered before prescribing Gemcitabine routinely as a second-line treatment for pancreatic cancer.

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Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure

Journal of Clinical Medicine ◽

10.3390/jcm8060761 ◽

2019 ◽

Vol 8 (6) ◽

pp. 761 ◽

Cited By ~ 3

Author(s):

Naoki Mita ◽

Takuji Iwashita ◽

Shinya Uemura ◽

Kensaku Yoshida ◽

Yuhei Iwasa ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Events ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Secondary Endpoints ◽

Grade 3 ◽

First Line Treatment

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. Aims: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. Methods: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). Results: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. Conclusion: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

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FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920947970 ◽

2020 ◽

Vol 12 ◽

pp. 175883592094797

Author(s):

Francesca Foschini ◽

Fabiana Napolitano ◽

Alberto Servetto ◽

Roberta Marciano ◽

Eleonora Mozzillo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Optimal Sequence ◽

Line Chemotherapy

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.

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

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920977155 ◽

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.

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

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919850367 ◽

2019 ◽

Vol 11 ◽

pp. 175883591985036 ◽

Cited By ~ 14

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.

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

10.21203/rs.3.rs-130888/v1 ◽

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

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