Role of second-line gemcitabine after FOLFIRINOX failure in advanced pancreatic adenocarcinoma: A retrospective analysis.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 473-473
Author(s):  
Aline Da Rocha Lino ◽  
Rodnei Merlrina Martins Junior ◽  
Carina Mina Abrahao ◽  
Raphael Brandao Moreira ◽  
Tarcia Tarciane Soares de Sousa ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Advanced Pancreatic Adenocarcinoma

473 Background: Cancer of the exocrine pancreas is a highly lethal malignancy. Based on a phase III study, FOLFIRINOX regimen became the standard first-line treatment for patients with good performance status. However, the optimal management strategy for patients who fail initial FOLFIRINOX remains undefined. We aim at reporting our experience with single-agent gemcitabine as a second-line treatment for advanced pancreatic cancer patients who progressed on FOLFIRINOX. Methods: Patients with advanced exocrine pancreatic adenocarcinoma who received gemcitabine (1.000 mg/m² on days 1, 8 and 15 every 4 weeks) until disease progression, as second-line therapy after FOLFIRINOX failure at our institution were retrospectively evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 20 patients were reviewed. Most of them (60%) had metastatic disease while 40% had locally advanced tumors. Median age was 60 years (range 43–74) and 80% were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1 in 65% and 2 or 3 in 35% of the patients. Median time on prior FOLFIRINOX therapy was 5 months. Median PFS and OS with gemcitabine were 2,0 (95% CI 1,2-2,8) and 5,7 months (95% CI 3,9-7,4), respectively. There were no deaths due to the treatment. Conclusions: In this study, gemcitabine was a reasonable second-line treatment option for patients with advanced pancreatic adenocarcinoma. Phase III trials are urgently needed exploring the role of gemcitabine in the second-line setting.

A randomized trial of gemcitabine (G) versus G plus cisplatin in chemotherapy-naive advanced pancreatic adenocarcinoma: The GIP-1 (Gruppo Italiano Pancreas— GOIM/GISCAD/GOIRC) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4504-4504
Author(s):  
G. Colucci ◽  
R. Labianca ◽  
F. Di Costanzo ◽  
V. Gebbia ◽  
G. Cartenì ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Clinical Benefit ◽  
Karnofsky Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Haematological Toxicity ◽  
Phase Iii ◽  
Line Treatment ◽  
Advanced Pancreatic Adenocarcinoma

4504 Background: Single-agent gemcitabine (G) remains standard treatment for advanced pancreatic adenocarcinoma (APC). The GIP-1 randomized phase III trial (clinicaltrials.gov ID NCT00813696 ) was performed to compare the combination of cisplatin (P) and G vs. G alone as 1st-line treatment. Methods: Patients (pts) with locally advanced and/or metastatic pancreatic adenocarcinoma, age 18–75, Karnofsky Performance Status (KPS) ≥50, were randomized to receive G (arm A) or G+P (arm B). In arm A, G was administered at 1000 mg/m2 weekly for 7 consecutive wks, and, after a 2-week rest, on day 1, 8, 15 every 4 wks. In Arm B, P 25 mg/m2 weekly (with the exception of day 22) was added to G, same dose used in Arm A (Colucci et al, Cancer 2002; 94:902–10). No maximum number of cycles was planned. Primary endpoint was overall survival (OS). Clinical benefit (CB), objective response rate (ORR), progression-free survival (PFS), toxicity and quality of life were secondary endpoints. To have 80% power of detecting a 0.74 Hazard Ratio (HR) of death (corresponding to increase in median OS from 4.8 to 6.5 months, with bilateral alpha=0.05, 400 pts were planned and 355 deaths were required for final analysis. Results: From April 2002 to April 2007, 400 pts were enrolled (A:199, B; 201) in 46 Italian Institutions. Median age was 63 yrs (range 35–75), 59% were males, 84% stage IV, 83% KPS≥80. After a median follow-up of 38.2 months and 357 deaths, median OS was 8.3 vs 7.2 months in arm A and B, respectively (HR 1.10, 95% CI 0.89–1.35, p=0.38). Median PFS was 3.9 vs 3.8 months in arm A and B, respectively (HR 0.97, 95% CI 0.80–1.19, p=0.80). ORR was 10.1% in arm A and 12.9% in B (p=0.37). CB response was experienced by 23.0% and 15.1% (Arm A vs B, p=0.057). Patients assigned to combination arm experienced more anaemia (all grades: 50% vs 39%, G3: 5% vs 1%), more neutropenia (all grades: 44% vs 36%, G3&4: 25% vs 14%) and more thrombocytopenia (all grades: 57% vs 29%, G3&4: 16% vs 5%). No relevant differences were seen in non-haematological toxicity. Conclusions: Weekly combination of P and G, compared to single-agent G as 1st-line treatment of APC, failed to demonstrate any improvement in OS, PFS, ORR and clinical benefit. No significant financial relationships to disclose.

Gemcitabine and nab-paclitaxel retreatment as a third-line therapy following second-line FOLFIRINOX for advanced pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15794-e15794
Author(s):  
Andrew Peter Dean ◽  
Adarsh Das ◽  
Meabh McNulty ◽  
Domenic Higgs
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Third Line Therapy ◽  
Third Line ◽  
Advanced Pancreatic Adenocarcinoma ◽  
Third Line Treatment

e15794 Background: First-line and second line treatment for advanced pancreatic adenocarcinoma typically involves therapy with gemcitabine plus nab-paclitaxel, FOLFIRINOX or as per the recent phase III trial (NAPOLI-1), the combination of nal-irinotecan with 5-fluorouracil and leucovorin. Despite these advances, there remains minimal amount of data regarding the options for, or efficacy of, third-line treatment in these patients. We have previously reported our experience of twenty patients who received effective third-line therapy with gemcitabine plus nab-paclitaxel retreatment after receiving FOLFIRINOX as second-line treatment. This retrospective analysis assessed the updated data of the use of gemcitabine plus nab-paclitaxel as a third-line treatment option in a single hospital setting. Methods: We conducted a retrospective analysis using an electronic database of patients with locally advanced or metastatic pancreatic adenocarcinoma who received first-line gemcitabine and nab-paclitaxel, second line FOLFIRINOX and third-line retreatment with gemcitabine and nab-paclitaxel between January 2013 and December 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Twenty-six patients were reviewed. Median age of 73 (range, 45 – 81). 73% of the studied patients had locally advanced cancer at diagnosis. The median OS from diagnosis was 39.0 months (95% CI, 34.0 – 66.0). The median OS from third-line re-initiation of gemcitabine plus nab-paclitaxel was 18.0 months (95% CI, 9.0 – 32.0). Conclusions: This is one of the first retrospective studies to show the efficacy of third-line treatment with gemcitabine plus nab-paclitaxel in advanced pancreatic cancer. It demonstrated that retreatment with gemcitabine plus nab-paclitaxel is feasible, tolerable and effective in patients with a good performance status. We suggest a formal phase 3 study to confirm our data and potentially establish a formal new standard of care for third line chemotherapy in this previously disadvantaged group.

Three fluoropyrimidine-based regimens in second-line therapy following nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer: Efficacy and tolerance in clinical practice.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 370-370
Author(s):  
Anne Laure Pointet ◽  
David Tougeron ◽  
Simon Pernot ◽  
Astrid Pozet ◽  
Dominique Bechade ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Statistical Significance ◽  
Performance Status ◽  
Locally Advanced ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
Secondary Resection ◽  
Kaplan Meier ◽  
Metastatic Sites

370 Background: Combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a valid first-line treatment (1L) in metastatic pancreatic adenocarcinoma (MPA) in patients (pts) with performance status (PS) of 0,1 or 2, but there is currently no standard second-line treatment (2L) after this new 1L option. We evaluated survival outcomes and tolerability of three usual fluoropyrimidine-based regimens: FOLFOX, FOLFIRI or FOLFIRI.3 (FOLFIRI1/3), and FOLFIRINOX after N+G failure in MPA pts. Methods: We prospectively identified 138 pts from 11 French centers who received 1L N+G for unresectable pancreatic adenocarcinoma. After disease progression or unacceptable toxicity, we excluded pts with locally advanced cancer, or who underwent secondary resection/chemoradiotherapy. Three subgroups of 2L chemotherapy were identified: FOLFOX, FOLFIRI1/3 and FOLFIRINOX regimens. Response was evaluated by RECIST criteria, progression-free survivals (PFS1, PFS2), and overall survival (OS1, OS2) were calculated using Kaplan-Meier method and compared with the Log-rank test. Results: 61 pts with MPA received a 2L. Persistent neuropathy was present in 27% of pts. Median age was 71.7 years [41-83]. PS was 0, 1 or 2. Median 1L duration, number of metastatic sites, PS, CA19.9, albumin, and bilirubin levels, and persistent neuropathy grade were statistically comparable between the 3 subgroups. Median OS for all 2L pts was 6.0 months [4-8]. Third line regimen was used in 32.8% of 2L pts without statistical significance between the subgroups. Main grade 3/4 adverse events reported were thrombocytopenia (18%), anemia (7.7%), neutropenia (21.4%) and nausea (5.4%). No toxic deaths occurred. Conclusions: This study suggests a clinical benefit and a manageable toxicity profile of 2L fluoropyrimidine-based regimens after N+G failure in patients with MPA, in particularly combined with irinotecan.[Table: see text]

Modified FOLFIRINOX as a second-line treatment in pancreatic adenocarcinoma patients with poor performance status.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15796-e15796
Author(s):  
Adarsh Das ◽  
Andrew Peter Dean ◽  
Domenic Higgs
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Metastatic Pancreatic Adenocarcinoma

e15796 Background: FOLFIRINOX is well known to be a highly effective treatment in pancreatic cancer for young patients with good performance status. As the original ACCORD study was carried out with patient’s performance status 0 or 1, many oncologists feel uncertain administering modified dose FOLFIRINOX (m-FOLFIRINOX) as a second-line therapy. We have previously reported our experience in 35 patients (aged 27 – 85) where we concluded that m-FOLFIRINOX can be administered safely with appropriate dose reductions. More recently, the systematic review and meta-analysis by Tong et al. concluded that m-FOLFIRINOX is a good choice of therapy even for those with poor performance status. This retrospective analysis assessed the efficacy of m-FOLFIRINOX in second-line treatment of pancreatic adenocarcinoma. Methods: Using an electronic database, patients with either locally advanced or metastatic pancreatic adenocarcinoma were identified who had received first-line gemcitabine plus nab-paclitaxel, followed by second-line m-FOLFIRINOX between January 2013 and July 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Fifty-two patients were identified, with 65% of the patients having metastatic pancreatic disease. Median age of patients was 75 (range, 27 – 86). Dose intensity of m-FOLFIRINOX was 65% for oxaliplatin, 68% for irinotecan, 18% for bolus 5-fluorouracil (5-FU) and 68% for infusional 5-FU. From diagnosis, the median OS of all patients was 45.0 months (95% CI, 25.0 – 63.0). The median OS of the locally advanced and metastatic pancreatic adenocarcinoma was 63.0 months (95% CI, 45.0 – 70.0) and 22.5 months (95% CI, 18.0, 38.0), respectively. Conclusions: Our study demonstrates the safety and efficacy of m-FOLFIRINOX as a second-line therapy after gemcitabine plus nab-paclitaxel failure. These findings correlate with the findings of Tong et al.’s findings of the benefits of m-FOLFIRINOX for advanced pancreatic cancer in patients with poor performance status.

Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium

2006 ◽  
Vol 24 (21) ◽  
pp. 3451-3457 ◽  
Author(s):  
Christopher J. Sweeney ◽  
Bruce J. Roth ◽  
Fairooz F. Kabbinavar ◽  
David J. Vaughn ◽  
Michael Arning ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Neoadjuvant Treatment ◽  
Previous Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Grade 3

Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4666-TPS4666
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Geert-Yan Creemers ◽  
Antonio Cubillo ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. 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. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). 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. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS783-TPS783
Author(s):  
Pascal Hammel ◽  
Rossana Berardi ◽  
Eric Van Cutsem ◽  
Jaime Feliu ◽  
Richard Greil ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Phase 3

TPS783 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. 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. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment. 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. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. Clinical trial information: NCT03665441.

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