Sequence therapy in metastatic pancreatic cancer

2018 ◽  
Vol 56 (06) ◽  
pp. 578-582 ◽  
Author(s):  
Oliver Waidmann ◽  
Uwe Pelzer ◽  
Stefan Boeck ◽  
Dirk-Thomas Waldschmidt
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Therapeutic Option ◽  
Standard Of Care ◽  
New Combination ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
Combination Therapies ◽  
First Line ◽  
Cancer Diseases

AbstractPancreatic cancer is one of the most lethal cancer diseases. For years, gemcitabine has been the standard of care and the only therapeutic option in patients with metastatic pancreatic cancer. Within the last years, new combination therapies have been established for first-line treatment, which significantly improve overall survival in comparison to gemcitabine monotherapy. Furthermore, new second-line therapies have been identified, which significantly improve overall survival. The current manuscript summarizes briefly standard of care first- and second-line chemotherapies and discusses possible treatment sequences.

Clinical outcomes of FOLFIRINOX and gemcitabine-nab-paclitaxel for metastatic pancreatic cancer in the real-world setting.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 656-656
Author(s):  
Fabio Franco ◽  
Jose Ignacio Martin Valades ◽  
David Marrupe ◽  
Juan Carlos Camara ◽  
David Gutierrez Abad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Elderly Population ◽  
Survival Rates ◽  
The Elderly ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
The Real ◽  
Ca 19.9

656 Background: Randomized clinical trials have established new chemotherapeutic standards of care for metastatic pancreatic cancer, namely FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GNP) after demonstrating a significant and relevant increase of overall survival. However, there are some important uncertainties regarding how many patients are candidate to each of the two new regimens in the real life and how is the pattern of use in the elderly population. Methods: This is a retrospective study. Departments of Pharmacy of 7 Spanish hospitals generated the listings of patients (pts) treated in first line with these new regimens (FFX or GNP). Non-metastatic patients were excluded. An exploratory analysis was performed in the elderly population. Results: From Jan 2012 to Dec 2017, a total of 119 pts (M/F 58/42 %) were treated. Med age 63 y (38-83 y), 99% adenocarcinoma. 40% located in the head of pancreas. ECOG 87% 0-1. 89% had liver mets. In the 1st line 49.6% were treated with FFX and 50.4% with GNP. 53% of the pts could receive a 2nd line (82% after FFX 75% after GNP). The median OS was 12 months with no statistically significant differences between both regimens (12,7m for FFX vs 10,2 m for GNP). Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70 yo. 13 (41%) were treated with FFX and 19 (59%) with GNP. The median OS for patients older than 70 was 9.5m versus 12.3m for patients younger than 70. Conclusions: In our setting the use of FFX and GNP for treating metastatic pancreatic cancer is quite similar. Superiority could not be demonstrated for any of the schemes in first-line. Overall survival was determined by basal Ca 19.9 and NLR. Patients receiving both regimens (FFX or GNP) in first/second line whichever the sequence, exhibited the best survival rates. In our series elderly patients had poor survival rates.

Anlotinib Plus Toripalimab and Nab-Paclitaxel in Patients with Locally Advanced or Metastatic Pancreatic Cancer: Study Protocol for An Open-Label, Non-Randomized, Phase II Study (ATNPA)

2021 ◽  
Author(s):  
Jingwen Chen ◽  
Yiqian Liu ◽  
Yizhi Zhu ◽  
Shiyun Cui ◽  
Chongqi Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Maintenance Therapy ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Combination Strategy

Abstract Background There have not been standard second-line or maintenance regimens with definite survival benefits so far for patients with pancreatic carcinoma who have lost the opportunity of curable resections or failed first-line chemotherapy. Anlotinib, a potent small-molecule tyrosine kinase inhibitor, exhibits anti-angiogenic and anti-tumour effects by specifically binding to multiple targets such as VEGFR, FGFR, PDGFR, c-Kit and Ret. Toripalimab, a novel anti-PD-1 mAb, has been proved to significantly prolong progression-free survival (PFS) and overall survival (OS) in various solid tumours with manageable toxicities when combining with cytotoxic chemotherapy. We design this study to assess the combination of anlotinib, toripalimab and nab-paclitaxel as a second-line or maintenance therapy for locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC). Patients and Methods: This is an open-label, non-randomized, single-arm phase Ⅱ study, aimed at evaluating the efficacy and safety profile of the above-mentioned combination strategy in first-line therapy-failed LAPC or MPC. Totally 53 patients are to be enrolled and receive anlotinib (12 mg, po. qd.) plus toripalimab (240 mg, ivgtt. q3w.) and nab-paclitaxel (125 mg/m2, ivgtt, d1, d8) every 3 weeks as a cycle until disease progression or intolerable adverse events. The primary endpoint is PFS. Secondary end points include OS, disease control rate (DCR), object response rate (ORR), quality of life (QoL) and safety. Enrollment started in April 2021, and follow-up will be finished in April 2023. Discussion and Significance: Combination of anlotinib, toripalimab and nab-paclitaxel may promote vessel normalization and drug delivery, and activate the immune response, thus exerting synergistic anti-tumour effects and counteracting the immunosuppressive microenvironment of pancreatic cancer. As the first intending to assess this combination in pancreatic cancer, this study will provide comprehensive evidence for second-line or maintenance therapy of LAPC and MPC. Trial registration: ClinicalTrials.gov: ATNPA, NCT04718701. Registered January 22, 2021. (https://clinicaltrials.gov/ct2/show/NCT04718701?term=NCT04718701&draw=2&rank=1)

A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 315-315 ◽  
Author(s):  
R. S. McDermott ◽  
P. Calvert ◽  
M. Parker ◽  
G. Webb ◽  
B. Moulton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Survival Duration ◽  
Synergistic Activity ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

Pulsed high-dose erlotinib with gemcitabine as second-line therapy for pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 421-421
Author(s):  
Christopher Larson ◽  
Tony R. Reid
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Dose Escalation ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Recommended Phase Ii Dose

421 Background: The options for treatment of pancreatic cancer follow progression on first line therapy are limited and associated with significant toxicity. Erlotinib has been approved for treatment of pancreatic cancer in first-line therapy. We conducted a phase I dose-escalation trial of erlotinib in combination with gemcitabine for patients that had failed first-line therapy. Erlotinib was administered by a novel pulse-dose schedule where the drug was given orally for 3 days every two weeks. Purpose: Assess the safety and determine a recommended phase II dose for pulsed high dose erlotinib in combination with gemcitabine for pancreatic cancer, and obtain preliminary data on activity. Methods: Patients with pancreatic cancer that progressed on or after first-line therapy were treated in a dose escalation study with erlotinib at 750 to 2,000 mg daily for three days every two weeks in combination with weekly gemcitabine at 1,000 mg/m2 for three weeks on and one week off. Results: No dose limiting toxicities were encountered and erlotinib-induced rash was mild and transient. Median overall survival was 6.7 months and 12-month overall survival was 27%. Progression free survival but not overall survival was longer in patients who did not previously receive gemcitabine. Rash was not associated with longer survival. Conclusions: The recommended phase II dose is erlotinib 2,000 mg daily for three consecutive days every two weeks in combination with gemcitabine. Tolerability was excellent, and outcomes were better than expected for second-line therapy in pancreatic cancer. Further studies are warranted, both as therapy after first-line and as first-line therapy for patients unable to tolerate more aggressive regimens. Clinical trial information: NCT02154737.

Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial

2014 ◽  
Vol 32 (23) ◽  
pp. 2423-2429 ◽  
Author(s):  
Helmut Oettle ◽  
Hanno Riess ◽  
Jens M. Stieler ◽  
Gerhard Heil ◽  
Ingo Schwaner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Karnofsky Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Gemcitabine Refractory

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

scholarly journals Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giandomenico Roviello ◽  
Monica Ramello ◽  
Martina Catalano ◽  
Alberto D’Angelo ◽  
Raffaele Conca ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Common Side Effect ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Toxicity Criteria

Abstract Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

scholarly journals Impact of New Chemotherapy Regimens on the Treatment Landscape and Survival of Locally Advanced and Metastatic Pancreatic Cancer Patients

2020 ◽  
Vol 9 (3) ◽  
pp. 648 ◽  
Author(s):  
Markus Kieler ◽  
Matthias Unseld ◽  
Daniela Bianconi ◽  
Martin Schindl ◽  
Gabriela V. Kornek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Survival Rates ◽  
Cox Proportional Hazards Model ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
First Line

Background: New chemotherapy regimens for the treatment of metastatic pancreatic cancer have changed the therapy paradigm. We aimed to assess their impact on the treatment landscape and clinical outcome at our academic institution. Methods: In this single institutional posthoc registry analysis, we assessed characteristics and survival rates from all patients with locally advanced and metastatic pancreatic cancer who started a systemic treatment between 01/2011 and 12/2017. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. Results: A total of 301 patients started a systemic treatment in the observation period. In the first line treatment, we observed a shift from the four different main regimens (gemcitabine/nab-paclitaxel, modified FOLFIRINOX, gemcitabine/oxaliplatin +/− erlotinib or gemcitabine alone) to gemcitabine/nab-paclitaxel and modified FOLFIRINOX that add up to more than 80% of administered first line treatments in each of the time cohorts (2011–2013 vs. 2014–2017). The rate for first line modified FOLFIRINOX treatment was balanced between the two groups (19% and 15%). Median overall survival differed significantly between the two time cohorts (8.89 versus 11.9 months, p = 0.035). Survival rates for different first to second line treatment sequences (modified FOLFIRINOX to gemcitabine/nab-paclitaxel, gemcitabine/nab-paclitaxel to fluoropyrimidines plus nanoliposomal irinotecan, or gemcitabine/nab-paclitaxel to fluoropyrimidines plus oxaliplatin) were not significantly different and median overall survival ranged from 14.27 to 15.64 months. Conclusion: Our study provides real-world evidence for the effectiveness of the new chemotherapy regimens and underscores the importance of the choice of the front-line regimen when considering different sequencing strategies.

Second-line therapy with pemetrexed after gemcitabine failure in patients with unresectable locally advanced or metastatic pancreatic cancer: A multicenter phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4124-4124 ◽  
Author(s):  
S. Boeck ◽  
K. Weigang-Koehler ◽  
M. Fuchs ◽  
E. Kettner ◽  
D. Quietzsch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Phase Ii ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

4124 Background: There is no established second-line therapy for advanced pancreatic cancer after failure of standard first-line treatment with gemcitabine. In view of the urgent need of such therapy and the observation of clinically meaningful responses with pemetrexed in previously untreated pancreatic cancer, this phase II study evaluated pemetrexed as second-line therapy. Methods: This study was planned to evaluate the efficacy and safety of pemetrexed in 54 patients (pts) with unresectable locally advanced or metastatic pancreatic cancer (stage II-IV), ECOG performance status ≤2 and estimated life expectancy of ≥12 weeks (wks) after failure of first-line gemcitabine single agent or combination therapy. Pemetrexed was started at 500 mg/m2 q3w (10 min infusion), with vitamin B12 and folic acid supplementation. Dose escalation by 100 mg/m2 every other cycle and an unlimited number of cycles were allowed. Primary endpoint was the 3-month survival rate. Results: A total of 189 treatment cycles (median 2, range 1–20) was given to 52 pts (60% male, median age 63 yrs, median time since initial diagnosis 32 wks, 89% stage IV disease). Doses were escalated in 2 pts (4%) and reduced due to toxicity in 9 pts (17%); median dose per cycle was 500 mg/m2 (range 212–700 mg/m2). The 3-month survival rate was 75% (95% CI 63.2–86.8%). At a median follow-up of 20 wks, the median overall survival estimate was 20 wks, with 9 pts alive including 1 still on pemetrexed. Median TTP was 7 wks (range 1–62 wks). The overall response rate was 3.8% (0 CR, 2 PR); 12 pts (23%) had SD for ≥6 wks, 9 of them for ≥12 wks. CA 19–9 decreased at least once by ≥ 50% in 12 pts (23%). Grade 3/4 hematological toxicity rates per pt were as follows: neutropenia 17.3% (febrile neutopenia: 3.8%), leukopenia 15.4%, thrombopenia 5.8% and anemia 3.8%. Conclusion: Pemetrexed is a feasible option for second-line therapy with mild toxicity and encouraging activity in unresectable locally advanced or metastatic pancreatic cancer after gemcitabine failure. [Table: see text]

Effect of the addition of platinum to gemcitabine on outcome in patients with advanced pancreatic cancer who progress on gemcitabine: A comprehensive analysis of published trials.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 275-275
Author(s):  
Osama E. Rahma ◽  
David J. Liewehr ◽  
Seth M. Steinberg ◽  
Austin G. Duffy ◽  
Tim F Greten
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Standard Of Care ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
General Search ◽  
Line Setting

275 Background: Pancreatic cancer is one of the deadliest cancers with an estimated 5 years survival rate of 5%. Until recently gemcitabine had been considered the first line treatment for locally advanced or metastatic disease. Although many chemotherapy regimens have been used there is no standard of care for second line therapy. The aim of this analysis was to identify superior regimen in the second line setting. Methods: We conducted a general search on PubMed for “second line therapy in advanced pancreatic cancer”. We limited our search to trials published in English from 2000 through 2012. Studies presented as abstracts in major meetings were also included. Trials that used targeted therapy other than erlotinib were excluded. We compared in an exploratory fashion the RR, PFS and OS of BSC and each of the following regimens to the rest of the treatments: 5FU+platinum, gemcitabine+platinum, taxol, erlotinib. In addition, we compared the combinations of platinum with either 5FU or gemcitabine. Finally, we explored the trend of these treatments outcomes over time. Results: Forty-four trialswere identified, of which 34 trials (T) met the inclusion criteria treating 1503 patients (N). There was a trend toward an improved overall survival with treatments (T: 33; N: 1269) compared to BSC (T: 2; N: 234) only (P= 0.013). The combination of gemcitabine and platinum (T: 5; N: 154) was the only regimen that showed a trend toward superior outcomes compared to the other regimens (T: 28; N: 1115) in terms of RR and PFS (P= 0.006 and 0.059, respectively). However, there was no difference in overall survival (P= 0.10). When compared to 5FU+platinum (T: 12; N: 450) the regimen of gemcitabine+platinum (T: 5; N: 154) showed only a trend toward significance in terms of improved RR (P= 0.030) with no difference in PFS or OS (P= 0.60 and 0.22, respectively). Overall, there was a trend toward a worse RR and PFS with no change in OS over the past 13 years. Conclusions: The combination of gemcitabine and platinum may provide a valid second line option in patients with locally advanced or metastatic pancreatic cancer who progress on gemcitabine.

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