scholarly journals Comparing real-world evidence among patients with metastatic pancreatic ductal adenocarcinoma treated with liposomal irinotecan

2020 ◽  
Vol 12 ◽  
pp. 175883592094405
Author(s):  
Jim Koeller ◽  
Andy Surinach ◽  
Steven R. Arikian ◽  
Marko Zivkovic ◽  
Patrick Janeczko ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Real World ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Poor Performance Status ◽  
Real World Evidence ◽  
Liposomal Irinotecan

There are questions surrounding the real-world effectiveness of chemotherapeutic treatments for pancreatic ductal adenocarcinoma. This literature review compared the clinical characteristics and outcomes of available real-world evidence (RWE) for liposomal irinotecan in combination with 5-fluorouracil (5-FU) and leucovorin (LV), a treatment regimen indicated for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously progressed on gemcitabine-based therapy. A targeted literature search was conducted in the PubMed Central® and Embase® databases to identify available RWE regarding patients with mPDAC receiving liposomal irinotecan published within the last 5 years (January 2014–September 2019). Data were extracted for prior lines of therapy, performance status, overall survival (OS), progression-free survival (PFS), duration of exposure, and adverse events. Six studies met inclusion criteria. A comparison of baseline patient characteristics and results with the included evidence reveals a clinically fragile, real-world patient population in terms of age (range: 61–68), prior lines of therapy with 34–61% of patients receiving ⩾2 lines of lines of prior therapy and performance status [49.8–100% of patients with Eastern Cooperative Oncology Group (ECOG) 0–1]. Studies observed wide OS (range: 5.3–9.4 months) and similar PFS (range: 2.3–4.1 months), with two studies measuring duration of exposure (7.3 weeks, 3.1 months). Patients analyzed by RWE studies tended to be older with significant disease progression, poor performance status, and more heavily pretreated compared with the phase III registrational trial (NAPOLI-1). Despite this, patients treated with liposomal irinotecan + 5-FU/LV therapy had similar outcomes as those in NAPOLI-1.

scholarly journals Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan

2021 ◽  
Vol 11 ◽  
Author(s):  
Kenneth H. Yu ◽  
Andrew E. Hendifar ◽  
Olatunji B. Alese ◽  
Amber Draper ◽  
Maen Abdelrahim ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Outcomes ◽  
Real World ◽  
Performance Status ◽  
Retrospective Chart Review ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Real World Data ◽  
Metastatic Setting ◽  
Liposomal Irinotecan

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score <2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively.ConclusionsPatients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study

2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  
Keyword(s):  
Performance Status ◽  
Real Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Ecog Ps ◽  
Prognostic And Predictive Markers

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

scholarly journals Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hakon Blomstrand ◽  
Karin Adolfsson ◽  
Per Sandström ◽  
Bergthor Björnsson
Keyword(s):  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Palliative Chemotherapy ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Ductal Adenocarcinoma ◽  
Second Line ◽  
First Line

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

scholarly journals Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Weekly Schedule ◽  
Dose Reductions

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

scholarly journals Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group

2019 ◽  
Vol 11 ◽  
pp. 175883591987112 ◽  
Author(s):  
Changhoon Yoo ◽  
Hyeon-Su Im ◽  
Kyu-pyo Kim ◽  
Do-Youn Oh ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Real World ◽  
Performance Status ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Liposomal Irinotecan

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

LAPACT: An open-label, multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS477-TPS477 ◽  
Author(s):  
Philip Agop Philip ◽  
Jill Lacy ◽  
Scot D. Dowden ◽  
Javier Sastre ◽  
Venu Gopal Bathini ◽  
...  
Keyword(s):  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Open Label ◽  
Primary Tumors

TPS477 Background: In pts with LAPC, more effective systemic therapies may be associated with improved local control, delay of metastasis, and overall survival (OS). The phase III MPACT trial in pts with metastatic PC demonstrated longer OS (median, 8.7 vs 6.6 mos; HR, 0.72; P < 0.001) and an ≈ 3-fold greater shrinkage of primary tumors with nab-P + Gem vs Gem alone (−22.15% vs −7.02%), raising the possibility of improved local PC control with nab-P + Gem. LAPACT will assess the efficacy and safety of nab-P + Gem in LAPC. Methods: LAPACT will enroll treatment-naive pts (planned n ≈ 110) in the United States, Canada, and Europe with Eastern Cooperative Oncology Group performance status ≤ 1, confirmed unresectable LAPC, no distant metastases, and adequate organ function. Pts with mixed-origin tumors, any other malignancy within 5 years, peripheral neuropathy grade > 1, or clinically significant ascites are ineligible. Pts will receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Pts without progressive disease (PD) or unacceptable toxicity after 6 cycles will receive investigator’s choice of surgery, chemoradiotherapy, or continued nab-P + Gem. If a major response is observed, surgery may occur prior to completing 6 cycles of nab-P + Gem. The primary endpoint is time to treatment failure (TTF; time from first therapy dose to discontinuation due to PD, start of a new non–protocol-defined anti-cancer therapy, or death). The study design allows for 80% power at a 1-sided α of 0.05 to detect a 30% increase over the 5.1-month median TTF observed for nab-P + Gem in the MPACT study. The secondary endpoints are disease control rate (DCR) after 6 cycles, overall response rate, progression-free survival, OS, safety, and quality of life. The exploratory endpoint is correlation of changes in circulating nucleic acids with PD and treatment response. An interim DCR analysis will occur after all pts have completed 6 cycles of nab-P + Gem, discontinued therapy due to PD, died, or started a new non–protocol-defined therapy before completing 6 cycles of therapy. Enrollment is ongoing (first pt enrolled in April 2015). Clinical trial information: NCT02301143.

Trends in checkpoint inhibitor therapy for advanced urothelial cell carcinoma (aUC) at the end of life: Insights from real-world practice.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Ravi Bharat Parikh ◽  
Matt D. Galsky ◽  
Bishal Gyawali ◽  
Fauzia Riaz ◽  
Tara Laura Kaufmann ◽  
...  
Keyword(s):  
End Of Life ◽  
Real World ◽  
Systemic Therapy ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Nonparametric Tests ◽  
Poor Performance Status ◽  
National Guidelines ◽  
Health Database

395 Background: National guidelines recommend against chemotherapy use at the end of life. Five CPIs are now approved for aUC. We hypothesized that oncologists may have a lower threshold to initiate CPI in patients (pts) at the end of life, particularly among pts with poor performance status (PS), because of the perceived favorable toxicity profile of CPI. Methods: We conducted a secular trend analysis using the Flatiron Health Database, a large real-world electronic medical record-derived dataset. We used nonparametric tests of trend (p values reported as ptrend) to evaluate quarterly proportions of pts initiating CPI, chemotherapy, or no systemic therapy within 30 and 60 days of death, among 2959 pts diagnosed with aUC from 2015 to 2017. Results: 1637 pts died during follow-up and were eligible for analysis. 278 (17.0%) and 488 (29.8%) pts initiated a new line of systemic therapy in the last 30 and 60 days of life, respectively. The quarterly proportion of CPI initiators within 60 days of death increased from 1.0% to 23% during the study period ( ptrend < 0.001), with corresponding decreases in chemotherapy initiation and no systemic therapy. After CPI approval in mid-2016, CPI initiation significantly increased among pts with Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 ( ptrend = 0.02) but did not significantly change among pts with PS 0-1. Initiation of any systemic therapy at the end of life doubled (17.4% to 34.8%) over the study period, driven largely by end-of-life CPI use. Compared to chemotherapy initiators, CPI initiators had slightly worse PS (table). Conclusions: In patients with aUC, there has been a dramatic rise in CPI initiation at the end of life particularly among pts with poor PS. Existing guidelines on systemic therapy initiation near the end of life should account for the increasing use of CPI. [Table: see text]

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