The impact of second-line chemotherapy on advanced pancreatic cancer: A retrospective study in Reggio Emilia Clinical Cancer Centre.

e15732 Background: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma. The aim of this study is to evaluate the impact of a second-line therapy prior to the introduction of nab-paclitaxel. Methods: From 01/2009 to 12/2014, 204 patients were treated for pancreatic cancer. 166 (81.3%) received first(I)-line chemotherapy. Patients treated in second(II)-line were evaluated in two different periods, before and after FOLFIRINOX introduction. Results: 99 patients (59.6% treated in I line) received II line therapy. The main regimens used in I line were gemcitabine during the period 2009-2011 and FOLFIRINOX from 2012 to 2014 (some patients were treated with nab-paclitaxel/gemcitabine approved before AIFA registration). We observed that the increased use of gemcitabine in the second period was related to a reduction in I line use (52.1% patients after 2012 vs 21.4% before 2012). Considering the different therapeutic regimens employed in I and II line, no statistically significant differences in overall survival were observed over the two periods (Table). The probability of receiving II line chemotherapy did not change in the two groups (HR 0.6; p=0.2). Conclusions: Within the limits of a retrospective analysis, all II line regimens used showed the same effectiveness, regardless of I line treatment employed. It is likely that the large number of patients treated with effective therapies in II line have concealed the impact of front-line schemes. In an ongoing study we are evaluating the impact of introducing nab-paclitaxel in clinical practice. [Table: see text]

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A randomized second line trial in patients with gemcitabine refractory advanced pancreatic cancer - CONKO 003

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4517 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4517-4517 ◽

Cited By ~ 8

Author(s):

H. Riess ◽

U. Pelzer ◽

J. Stieler ◽

I. Schwaner ◽

G. Heil ◽

...

Keyword(s):

Pancreatic Cancer ◽

Side Effects ◽

Disease Progression ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Second Line ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

The Impact

4517 Objective: For nearly ten years gemcitabine (G) was standard first line therapy for patients (pts) with advanced pancreatic cancer (APC). There is no consensus about second line therapy after disease progression while receiving G, but 5-FU-based regimens are considered. Results about randomized second line studies in APC are very rare. Our phase II study (ASCO 2002) showed activity of the OFF (oxaliplatin/folinic Acid (FA)/5-fluorouracil (FU) [24h] ) regimen in 23 pts. To examine the impact and the side effects of oxaliplatin we initiated a multicenter phase III study to compare OFF and FF in pts with G refractory APC. Methods: Pts with CT/ MRT confirmed failure with G in first line therapy, Karnofsky Performance Status (KPS) >60%, controlled pain, adequate hematological, renal and liver functions were eligible. Pts were stratified according to duration of first line therapy, KPS and tumor stage. We randomized pts to outpatient treatment with FF (FU 2g/m2 (24h)/ FA 200 mg/m2 (30min) on d1, d8, d15 and d22) or OFF (FF+Oxaliplatin 85mg/m2, d8, d22). In both arms the next cycle started on day 43. Pts were followed with regular staging every 3 months or at any signs of disease progression. Results: Until now we randomized 161 of 165 (planned) pts between 02/2004 and 01/2007. So we expect to present first results (side effects, progression free survival, overall survival) at the meeting. No significant financial relationships to disclose.

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Survival benefit of second-line chemotherapy in advanced pancreatic adenocarcinoma: A systematic review of the literature.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.296 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 296-296 ◽

Cited By ~ 1

Author(s):

Adnan Nagrial ◽

Venessa T. Chin ◽

Katrin Sjoquist ◽

Lorraine A. Chantrill ◽

Desmond Yip

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Single Agent ◽

Advanced Pancreatic Cancer ◽

Response Rates ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Chemotherapy ◽

Line Chemotherapy

296 Background: There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. Very few randomised studies have been performed in this setting. The aim of this analysis was to compare the different therapeutic approaches in this setting, and the rate of second line treatment delivery and its influence on reported overall survival. Methods: We carried out a systematic analysis of studies in advanced pancreatic cancer. 1st and 2nd line chemotherapy trials were identified from MEDLINE, EMBASE & CENTRAL using the COCHRANE sensitive search strategy. Objective response rates (ORR) and survival (PFS & OS) were extracted and compared amongst groups using the Mann-Whitney U test. For 1st line studies, the percentage of patients who received 2nd line chemotherapy was also extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. Results: 20 first line clinical trials with 42 treatment arms met the inclusion criteria treating an aggregate total of 5,768 patients. Overall survival was positively correlated with use of second-line chemotherapy (r=0.65; p=0.012). 61 second-line studies were identified treating an aggregate total of 2,562 patients in 66 treatment arms. Combination treatment was associated with an improved response rate (p=0.045) and PFS (p=0.024) when compared to single agent therapy. Conclusions: In this exploratory analysis, these data suggest that there is a small benefit of second-line chemotherapy in pancreatic cancer. In first-line chemotherapy studies, the use of subsequent treatment correlates with improved overall survival. In second line studies, combination chemotherapy is associated with higher response rates and survival.

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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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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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Multicenter Retrospective Analysis of Second-Line Therapy after Gemcitabine Plus Nab-Paclitaxel in Advanced Pancreatic Cancer Patients

Cancers ◽

10.3390/cancers12051131 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1131 ◽

Cited By ~ 2

Author(s):

Valeria Merz ◽

Alessandro Cavaliere ◽

Carlo Messina ◽

Massimiliano Salati ◽

Camilla Zecchetto ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Advanced Pancreatic Cancer ◽

Rank Test ◽

Second Line ◽

Second Line Therapy ◽

Clear Trend ◽

Line Therapy ◽

Kaplan Meier ◽

Number Of Patients

Pancreatic cancer is one of the most lethal solid tumors. In many European countries gemcitabine plus nab-paclitaxel is the preferred first-line treatment. An increasing number of patients are eligible for second-line therapy, but the best regimen is still controversial. This study aimed to evaluate the efficacy of oxaliplatin-based compared to irinotecan-based therapies in this setting. 181 advanced pancreatic cancer patients consecutively treated in three centers with a second-line therapy progressed on gemcitabine plus nab-paclitaxel were retrospectively enrolled. OS and PFS were calculated using the Kaplan-Meier method and survival of the two groups was compared using the log-rank test. The median PFS and OS were respectively 3.5 (95%CI 3.2–3.8) and 8.8 months (95%CI 7.9–9.8) from second-line therapy in the overall population. The median PFS and OS were respectively 3.3 (95%CI 3.1–3.5) and 8.2 months (95%CI 7.24–9.34) with an irinotecan-based combination compared to 4.0 (95%CI 2.4–5.7) and 10.3 months (95%CI 8.62–12.02) in patients receiving an oxaliplatin-based combination. We observed a clear trend for longer survival outcomes with platinum-based doublet compared to regimens including irinotecan or nal-IRI. Head-to-head trials are still lacking. The neutrophil-to-lymphocyte ratio and the presence of liver metastases could drive physicians in tailoring the treatment strategy.

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Clinical efficacy of apatinib as a second-line treatment for advanced pancreatic cancer in a Chinese tertiary cancer health facility

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i9.30 ◽

2021 ◽

Vol 18 (9) ◽

pp. 1993-1998

Author(s):

Ning Sun ◽

Chenchen Li ◽

Yun Zhou ◽

Lei Xia ◽

Xiaoming Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adverse Reactions ◽

Advanced Pancreatic Cancer ◽

Control Group ◽

Study Group ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Single Drug ◽

Line Therapy

Purpose: To study the effectiveness and safety of apatinib as second-line treatment for advanced pancreatic cancer (APC) in a Chinese tertiary cancer hospital. Methods: Two groups of APC patients who received treatment with single-agent or two-drug combination of gemcitabine-based first-line therapy (50 per group) in The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing were assessed. The study group received apatinib at or above the second line treatment, while the control group was treated with second-line chemotherapy, which was different from first-line single-drug chemotherapy. Patients received treatments until there was improvement in their conditions, or until adverse reactions became intolerable. Complete remission (CR), partial remission (PR), disease stabilization (SD), disease progression (PD), incidence of adverse reactions, and progression-free survival (PFS) of the patients were recorded. Results: The number of PR cases in APC patients who received apatinib as second-line therapy, and the number of PD patients were higher than the corresponding populations in the control group (p < 0.05). Treatment effectiveness was significantly higher in study group patients than in control subjects (p < 0.05). However, the incidence of adverse reactions was lower in the study group than in control group. Median PFS in the study group (5 months) was significantly higher than that of the control group (4.1 months, p < 0.05). Conclusion: The clinical efficacy of apatinib as second-line treatment for advanced pancreatic cancer is higher than that of the single drug. Apatinib is associated with low incidence of adverse reactions which prolongs PFS. Thus, apatinib has potentials for the clinical management of pancreatic cancer.

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Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15187 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15187-15187 ◽

Cited By ~ 1

Author(s):

T. Herrmann ◽

D. Jaeger ◽

W. Stremmel ◽

C. Herrmann

Keyword(s):

Pancreatic Cancer ◽

Disease Progression ◽

Stable Disease ◽

Partial Remission ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Chemotherapy ◽

Line Chemotherapy

15187 Background: Patients with advanced pancreatic cancer profit from palliative chemotherapy. The role of second-line chemotherapy is not yet established. Methods: We performed a retrospective analysis in 98 patients who were treated at our department from 1/2004–6/2006 due to locally advanced or metastatic adenocarcinoma of the pancreas. Results: At the time of analysis 67 patients had died (median overall survival 9 months), 31 patients are still alive (median follow up 9 months). 12 patients were initially treated with radiochemotherapy. 86 patients received systemic chemotherapy; 43 of these patients were treated with second-line chemotherapy after disease progression. OS was significantly longer in patients who received second-line chemotherapy (10 months versus 5.0 months, p=0.023). Response to second-line chemotherapy was partial remission in 2 patients (4.6 %), stable disease in 18 patients (44.8 %), and progressive disease in 19 patients (44.2 %), in 3 patients the treatment was stopped due to toxicity (6.9 %). 12 patients received second-line treatment after early disease progression under first-line chemotherapy. 9 of these patients did not respond to second-line treatment, 2 achieved stable disease and 1 patient had partial remission. Elevated LDH and CA19.9 serum levels at the time of diagnosis were identified as negative prognostic factors. Conclusions: Prognosis of patients with advanced pancreatic cancer is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.

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Beneficial trends of second-line chemotherapy in advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14680 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14680-e14680

Author(s):

Milton Jose B. Silva ◽

Joyce Maria L. Maia ◽

Adriana Regina G. Ribeiro ◽

Ludmilla T. D. Chinen ◽

Tadeu Ferreira Paiva Jr ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Advanced Pancreatic Cancer ◽

Control Analysis ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Chemotherapy ◽

Kaplan Meier ◽

Line Chemotherapy

e14680 Background: Despite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). Methods: We performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n = 49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (< 60y versus ≥ 60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method. Results: Median age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24,4%), followed by peritoneum (2,8%).Median follow-up of both groups was 8.4 months (0.23m-54.93m). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and gemcitabine + cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by Folfox (16.3%), and Fluoracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (p:0.021), and 60% vs. 32%, and 30% vs. 19% in SLC and FLC group, respectively. Conclusions: Our result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It’s important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.

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