Gemcitabine and nab-paclitaxel in older adults with metastatic pancreatic cancer: Are two doses per cycle enough?

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 655-655 ◽  
Author(s):  
Arthur Winer ◽  
Elizabeth A. Handorf ◽  
Efrat Dotan
Keyword(s):  
Older Adults ◽  
Pancreatic Cancer ◽  
Real World ◽  
Cox Model ◽  
Performance Status ◽  
Dose Intensity ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Dosing Schedule

655 Background: The dosing of Gemcitabine and Nab-Paclitaxel (GA), a frontline regimen to treat metastatic pancreatic cancer (mPC), is frequently altered from the traditional dosing schedule (TDS) of day 1, 8, and 15 of a 28 day cycle to a modified dosing schedule (MDS) of 2 doses/cycle. Previous work showed that overall survival (OS) was similar between patients (pts) treated with the MDS vs the TDS. We sought to analyze a larger real-world database to assess these trends. Methods: We retrospectively analyzed de-identified pts with mPC ≥ 65 y/o treated with GA in the Flatiron Health nationwide EHR-derived database. Demographics, treatments (tx), and outcomes were collected. Pts were grouped as either starting with the TDS or MDS. Analysis included time on treatment (TOT) as well as OS. A Cox model was used to test non-inferiority of the MDS vs the TDS for both TOT and OS, adjusting performance status, age, race, gender, and line of therapy (LOT). The upper bound for non-inferiority was a Hazard Ratio (HR) = 1.2. Results: 1497 pts were treated between 1/1/14-5/31/19; 883 pts with the TDS and 614 with the MDS. Median TDS age was 72 (65-85) and MDS was 73 (65-84) (p<0.001). 1237 pts received first- line GA; 60% received the TDS, 40% the MDS. The use of the TDS vs MDS did not vary significantly by LOT, gender, or race, but more pts with a PS of ≥2 received the MDS (p=0.03). In the first-line, outcomes were better for the TDS vs the MDS (unadjusted median TOT 5.3 vs 3.2 mo, p<0.001, OS 9.2 vs 5.3 mo; p<0.001), with consistent results in the ≥ second-line. The MDS did not meet its non-inferiority boundary: first-line TOT HR=1.4 [95% CI 1.2-1.6]; second+ line TOT HR=1.3 [95% CI 1.0-1.7]; first-line OS HR=1.6 [95% CI 1.4-1.8]; second+ line OS HR=1.3 [95% CI 1.0-1.8]. Results were consistent when additionally stratified by PS 0-1 vs 2+. Conclusions: In this large real-world cohort, first-line GA tx with a MDS did not meet criteria for non-inferiority for TOT and OS vs a TDS in older adults with mPC. With the caveats of potential confounding that exist in a de-identified retrospective database, these results suggest that dose intensity may be important in pts with mPC. Further prospective studies are necessary to ensure we utilize effective tx strategies in older adults with mPC.

scholarly journals Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update

2018 ◽  
Vol 36 (24) ◽  
pp. 2545-2556 ◽  
Author(s):  
Davendra P.S. Sohal ◽  
Erin B. Kennedy ◽  
Alok Khorana ◽  
Mehmet S. Copur ◽  
Christopher H. Crane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Comorbidity Profile

Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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)

Oral chemotherapy as second-line treatment option for gemcitabine-refractory advanced pancreatic cancer with poor performance status.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 405-405
Author(s):  
Se Jun Park ◽  
Myung Ah Lee
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Dose Intensity ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Median Dose ◽  
Gemcitabine Refractory

405 Background: There is few data for effective second-line treatment in advanced pancreatic cancer, and most patients have poor performance status after progressive disease. We evaluated the efficacy, toxicity, and median dose intensity of oral chemotherapy, capecitabine, or TS-1 in gemcitabine-refractory advanced pancreatic cancer for second-line treatment. Methods: Patients who have progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between Jan. 2011 and Nov. 2017. These patients were treated with capecitabine or TS-1 as second-line treatment. Capecitabine were administered as 2,500 mg/m2 divided dose on day 1-14, followed by one week rest. In TS-1 group, TS-1 was taken orally based on patient’s BSA (60mg twice daily in BSA > 1.5, 50mg twice daily in BSA 1.25-1.5, and 40mg twice daily in BSA < 1.25) through 28 days, by two week rest. Median dose intensity was compared by calculating a percent of target dose achieved in the average cycle for each patient. Results: Of the total 62 patients, 41 patients were treated with capecitabine and 21 patients were treated with TS-1. The median age was 61 years for the capecitabine group compared with 62 years for the TS-1 group. In capecitabine group, males were 56%, and in TS-1 group, males were 66%. 29% of capecitabine group received prior fluorouracil base therapy, and 47% of TS-1 group were receiving such therapy. The objective response rate was similar in the two groups: 12.2% with capecitabine and 4.8% with TS-1 (p = 0.358). There was no difference in median progression free survival between capecitabine and TS-1 (2.1 months vs. 2.7 months, p = 0.102), however, TS-1 group showed better median overall survival time than capecitabine group (6.9 months vs. 4.6 months, p = 0.048). Most of the adverse events were similar in both group, except that grade 3 or 4 mucositis was more common in TS-1 group. There was no significant difference in median dose intensity between two groups. (Capecitabine 91.5% vs. TS-1 90.1%, p = 0.216). Conclusions: Oral agents such as TS-1 or capecitabine can be second-line treatment for advanced pancreatic cancer patients with poor performance status after progression to gemcitabine-based regimen.

scholarly journals Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens

2020 ◽  
Author(s):  
Zev Aryeh Wainberg ◽  
Kynan Feeney ◽  
Myung Ah Lee ◽  
Andrés Muñoz ◽  
Antonio Cubillo Gracián ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Controlled Trials ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Similar Treatment ◽  
Randomized Controlled ◽  
Nanoliposomal Irinotecan

Abstract Background: Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)–based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy. Methods: PubMed.gov, FDA.gov, ClinicalTrials.gov, congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990–June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients. Results: Of 282 studies identified, 11 randomized controlled trials ( N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4–7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6–6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8–8.9). Neutropenia and fatigue were the most commonly reported Grade 3–4 TRAEs associated with FOLFOX. Conclusions: Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0–1) following gemcitabine treatment.

scholarly journals 1526P First and second-line palliative systemic treatment outcomes in a real-world metastatic pancreatic cancer cohort

2020 ◽  
Vol 31 ◽  
pp. S939-S940
Author(s):  
E. Pijnappel ◽  
W.P.M. Dijksterhuis ◽  
L. van der Geest ◽  
J. de vos-Geelen ◽  
J.W.B. de Groot ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Outcomes ◽  
Real World ◽  
Systemic Treatment ◽  
Metastatic Pancreatic Cancer ◽  
Second Line

scholarly journals Patterns of care in metastatic pancreatic cancer: patient selection in clinical routine

2019 ◽  
Vol 12 ◽  
pp. 175628481987763 ◽  
Author(s):  
Werner Scheithauer ◽  
Paul Martin Putora ◽  
Birgit Grünberger ◽  
Wolfgang Eisterer ◽  
Ewald Wöll ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Decision Trees ◽  
Patient Selection ◽  
Performance Status ◽  
Treatment Options ◽  
Metastatic Pancreatic Cancer ◽  
Decision Criteria ◽  
First Line ◽  
Clinical Routine ◽  
Treatment Algorithms

Background: The management of patients with metastatic pancreatic cancer (mPC) is challenging, and the optimal treatment strategy is debated among experts. In an attempt to identify treatment decision criteria and to investigate variations in the first-line management of this disease, we performed an analysis of treatment algorithms among experts in the field of pancreatic cancer. The aim of this study was to identify relevant criteria in the complex process of patient selection and decision making for the management of mPC patients. Methods: Experts from the ABCSG (Austrian Breast and Colorectal Cancer Study Group) Pancreatic Cancer Club were contacted and agreed to participate in this analysis. Eight experts from seven centers in Austria provided their decision algorithms for the first-line treatment of patients with mPC. Their responses were converted into decision trees based on the objective consensus methodology. The decision trees were used to identify consensus and discrepancies. Results: The final treatment algorithms included four decision criteria (performance status, age, comorbidities, and symptomatic disease) and six treatment options: mFOLFIRINOX, gemcitabine + nab-paclitaxel, gemcitabine mono, 5-FU mono, gemcitabine/erlotinib, and best supportive care (BSC). Conclusions: We identified consensus for the treatment of young and fit patients with mFOLFIRINOX. With higher age and reduced performance status, gemcitabine + nab-paclitaxel was increasingly used. For patients with Eastern Co-operative Oncology Group Performance Status (ECOG PS) 4, BSC was the treatment of choice. Among experts, different decision criteria and treatment options are implemented in clinical routine. Despite multiple options in current recommendations, a consensus for specific recommendations was identified.

scholarly journals Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

2019 ◽  
Vol 12 ◽  
pp. 175628481987866 ◽  
Author(s):  
Nicolas Williet ◽  
Angélique Saint ◽  
Anne-Laure Pointet ◽  
David Tougeron ◽  
Simon Pernot ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Propensity Score ◽  
Liver Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Reverse Sequence ◽  
Metastatic Sites

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

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