Consistent Response on Challenge and Rechallenge of Liposomal Irinotecan in a Patient with Metastatic Pancreatic Adenocarcinoma Previously Treated with Gemcitabine plus Nab-Paclitaxel: A Case Report

Approximately 80% of pancreatic cancer is diagnosed at an advanced stage, due to lack of or vague symptoms when the cancer is still localized, leading to a high mortality rate. Known risk factors for developing pancreatic cancer are family history, obesity, type 2 diabetes, and alcohol and tobacco use. There has been a remarkable development in diagnosis modalities and molecular testing, but early detection is still infrequent. The majority of clinical trials have not shown significant efficacy in pancreatic cancer, and treatment strategy remains limited. Additional prognostic factors should be highlighted to obtain appropriate treatment options, including precision medicine, and improve survival outcomes. After the PRODIGE study in 2011 and the MPAC trial in 2013, a new drug (liposomal irinotecan; Onivyde ®) appeared in the strategy, especially after failure of gemcitabine-based treatment. In 2016, the NAPOLI-1 trial showed evidence of the efficacy of the liposomal irinotecan combination (liposomal irinotecan +5-fluorouracile + folinic acid); now, it is considered the standard treatment for relapsing patients. Since NAPOLI-1, real-world data have provided similar results. Herein, we report the story of a 61-year-old woman who was treated with liposomal irinotecan combination (nal-IRI/5-FU/LV) for 8 months with good surgical response, but treatment was discontinued due to economic burden. After the start of treatment (or 1? cycle of liposomal irinotecan treatment), the patient was in a better condition. The liver metastases had disappeared. The combination with liposomal irinotecan was re-administered with patient’s approval. Upon rechallenge with the liposomal irinotecan combination, she showed a partial response, and the treatment was given for 7 months. In this report, we tried to identify the prognostic factors leading to the efficacy of the liposomal irinotecan combination.

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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

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919871126 ◽

2019 ◽

Vol 11 ◽

pp. 175883591987112 ◽

Cited By ~ 4

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.

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A randomized phase II and coagulation study of bevacizumab alone or with docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4556 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4556-4556 ◽

Cited By ~ 4

Author(s):

I. A. Astsaturov ◽

N. J. Meropol ◽

R. K. Alpaugh ◽

J. D. Cheng ◽

N. L. Lewis ◽

...

Keyword(s):

Pancreatic Cancer ◽

Growth Factor ◽

Pancreatic Adenocarcinoma ◽

Phase Ii ◽

Stable Disease ◽

Circulating Endothelial Cells ◽

Randomized Phase Ii ◽

Metastatic Pancreatic Adenocarcinoma ◽

Coagulation Study ◽

Previously Treated

4556 Background: Vascular endothelial growth factor (VEGF) is overexpressed in pancreatic cancer and interacts with coagulation to promote angiogenesis. We performed this randomized phase II study of bevacizumab (BEV) alone or with docetaxel (DOC) in patients (pts) with previously treated metastatic pancreatic adenocarcinoma to investigate their clinical activity and interaction with coagulation. Methods: Eligible pts had one prior gemcitabine regimen, PS 0–1, measurable disease, and no bleeding/thrombosis. BEV was given at 10 mg/kg IV Q 2 weeks alone (Arm A) or with DOC (Arm B) at 35 mg/m2 IV on days 1, 8, and 15 Q 28 days. CT scans were obtained every 2 cycles. The primary endpoint was progression-free survival (PFS), with secondary endpoints response rate and overall survival (OS). Peripheral blood was obtained for coagulation parameters, basic fibroblast growth factor (bFGF), VEGF, and circulating endothelial cells (CEC). A two-stage design with a target median PFS of =4 months in either arm and early stopping for futility was utilized. Results: Thirty pts (15 per arm) received 88 cycles of therapy (44 per arm, median 2, range <1–10). Pt characteristics: median age 61.5 (range 38–81), ECOG 0/1 (11/19). Seven pts in Arm A and 8 in Arm B had grade 3/4 events. Serious adverse events were 5 DVT/PE (3-Arm A; 2-Arm B) and 2 bowel perforations (1 per arm). Best reponse was 4 pts with stable disease in Arm A and 5 pts with stable disease and one unconfirmed PR in Arm B. Median PFS and OS were 43 and 181 days in Arm A and 45 and 123 days in Arm B (p=0.5 for PFS, p=0.8 for OS). The study was stopped after only 2/15 pts per arm had PFS of =4 months. In multivariate analysis, higher bFGF (HR=1.4, p=0.008) and thrombin/antithrombin complex (TAT) levels on treatment (HR=1.75, p<0.001) were associated with worse OS. D-dimer, tissue factor and TAT levels on d15 were associated with increased venous thrombosis and GI perforation (p=0.04). VEGF plasma levels and CEC at all time points were not associated with clinical outcomes. Conclusions: BEV alone or with DOC has minimal antitumor activity in gemcitabine-refractory pancreatic cancer. Increased plasma bFGF and coagulation markers during therapy predict for worse OS and increased perforation and thrombosis. [Table: see text]

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Observational retrospective evaluation of treatment with liposomal irinotecan plus fluorouracil/leucovorin for metastatic pancreatic cancer patients: An Italian large real-world analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.660 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 660-660 ◽

Cited By ~ 1

Author(s):

Antonio Pellino ◽

Chiara Manai ◽

Valeria Merz ◽

Mario Scartozzi ◽

Michele Milella ◽

...

Keyword(s):

Pancreatic Cancer ◽

Real World ◽

Cox Regression ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

Rank Test ◽

Efficacy And Safety ◽

Real World Data ◽

Liposomal Irinotecan ◽

Ecog Ps

660 Background: In the NAPOLI I phase III trial, Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed better outcome compared to 5FU/LV in patients with metastatic Pancreatic Cancer (MPC) progressed to 1st- line gemcitabine-based therapy. Aim of this study is to explore the real-world efficacy and safety of 5FU/LV-nal-IRI by a compassionate use programme and to identify potential prognostic factors that could affect survival in this setting. Methods: This is a retrospective multi-center analysis including patients with MPC who received 5FU/LV-nal-IRI after failure of a gemcitabine-based therapy. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariate analyses were performed by using the log-rank test and the Cox regression. Results: A total of 296 pts (median age, 69 years, range 30-82; 50% male; ECOG PS 0, 44%) were treated at 11 Italian institutions from June 2016 and November 2018. 34% of the pts have been previously resected on their primary tumor, and 76% received gemcitabine-nabpaclitaxel as 1st - line treatment. 5FU/LV-nal-IRI has been administered as 2nd - line in 72% of the pts, while in 23% of the cases as 3rd - line or more. The median OS was 7.1 months [95% confidence interval (CI) 6.1 - 8.1] and the median PFS was 3.3 months (95% CI 2.9 - 3.6). At six months, OS and PFS rate were 53.4% and 31.4% respectively. ORR was 12% and DCR was 40%. 52% of pts received more than 4 cycle with dose reduction in 148 pts (50%). Most common grade 3 toxicities were neutropenia (14%), diarrhea (11%), anemia (3%), nausea (3%), fatigue (3%), mucositis (2%) and vomiting (1%). Baseline characteristics associated with better OS were ECOG PS 0, normal CEA, neutrophil-to-lymphocyte ratio ≤5 and haemoglobin ≥11 g/dL. Conclusions: These real-world data confirm the efficacy and safety of 5FU/LV-nal-IRI in patients with MPC progressed to a gemcitabine-based therapy, with outcome comparable to NAPOLI-1 even in a less selected population and with more active 1st - line combination therapy. In this cohort, well known prognostic markers has been confirmed, as expected.

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Application of two lines of chemotherapy: gemcitabine with nab-paclitaxel and liposomal irinotecan with 5-fluorouracil and leucovorin in patient with advanced pancreatic adenocarcinoma

Oncoreview ◽

10.24292/01.or.123100721 ◽

2021 ◽

Vol 11 (3(43)) ◽

pp. 68-72

Author(s):

Krystyna Ostrowska-Cichocka ◽

Marek Z. Wojtukiewicz

Keyword(s):

Pancreatic Cancer ◽

Therapeutic Option ◽

Advanced Pancreatic Cancer ◽

Distant Metastases ◽

Phase Iii ◽

Phase Iii Study ◽

Previously Treated ◽

Liposomal Irinotecan ◽

Line Of Therapy ◽

Advanced Pancreatic Adenocarcinoma

Pancreatic cancer is a disease with high mortality. It is predicted to become the second leading cause of cancer death in some regions of the world. Frequent diagnosis at an advanced stage contributes to 5-year survival at a highly unsatisfactory level of 2–9%. Due to the lack of early symptoms, nearly 80% of patients receive a diagnosis when distant metastases develop. So far, the most frequently used programs in the treatment of patients with pancreatic cancer in the stage of neoplastic spreading include: FOLFIRINOX (oxaliplatin, 5-fluorouracil, irinotecan, leucovorin), gemcitabine alone or in combination with nab-paclitaxel or erlotinib. Based on the results of the phase III study NAPOLI-1, liposomal irinotecan in combination with 5-fluorouracil (5-FU) and leucovorin (LV ) was approved as the first regimen for use in the second or subsequent line of therapy in patients with advanced pancreatic cancer previously treated with gemcitabine. This paper presents a case of a patient with advanced pancreatic cancer who was treated with two lines of chemotherapy – gemcitabine in combination with nab-paclitaxel and liposomal irinotecan with 5-FU/LV . The treatment was well tolerated and was considered a valuable therapeutic option. A 2-year overall survival was obtained from the diagnosis of the disease.

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Clinical outcomes of liposomal irinotecan plus fluorouracil/leucovorin for metastatic pancreatic adenocarcinoma in patients previously treated with conventional irinotecan-containing chemotherapy

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211003053 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110030

Author(s):

Kyunghye Bang ◽

Jaekyung Cheon ◽

Jae Ho Jeong ◽

Hyeon-Su Im ◽

Kyu-pyo Kim ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Cumulative Dose ◽

Negative Correlation ◽

Objective Response ◽

Progression Free Survival ◽

Metastatic Pancreatic Adenocarcinoma ◽

Previously Treated ◽

Liposomal Irinotecan ◽

Grade 3 ◽

Median Cumulative Dose

Introduction: Liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has shown clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on gemcitabine-based chemotherapy. However, its role in patients with mPAC previously treated with conventional irinotecan-containing chemotherapy has not been appropriately investigated. Methods: In this retrospective analysis, patients with mPAC who received nal-IRI plus 5-FU/LV after conventional irinotecan-containing regimen between January 2017 and March 2020, were identified from two referral cancer centers in South Korea. The ratio of time to progression (TTP) with nal-IRI plus 5-FU/LV to TTP with conventional irinotecan (TTPr) was analyzed with respect to the duration and cumulative dose of conventional irinotecan treatment. Results: In total, 35 patients treated with nal-IRI plus 5-FU/LV after the irinotecan-containing regimen were analyzed. The median age was 58 years and 16 (46%) patients were male. The median duration of conventional irinotecan therapy was 4.6 months at a median cumulative dose of 1230 mg. The objective response rate of nal-IRI plus 5-FU/LV was 2.9%, and stable disease was achieved in 11 (31.4%) patients. During the median follow-up of 9.2 [95% confidence interval (CI): 7.8–10.5] months, the median progression-free survival (PFS) and overall survival (OS) were 2.0 (95% CI: 1.4–2.6) months and 4.4 (95% CI: 3.6–5.7) months, respectively. The 6-month PFS and OS rates were 16.3% and 37.5%, respectively. The median TTPr was 0.41 (range, 0.07–2.07), showing a negative correlation with the cumulative dose of prior irinotecan therapy (R = −0.37, p = 0.041). A tentative negative correlation between TTPr and duration of prior irinotecan therapy was observed ( R = −0.35, p = 0.062). The most common grade 3–4 toxicities were neutropenia (20%) and fatigue (8.6%). Conclusion: Nal-IRI plus 5-FU/LV showed modest effectiveness and manageable toxicities for patients with mPAC previously treated with conventional irinotecan-containing chemotherapy. The cumulative dose of prior conventional irinotecan therapy may be inversely correlated with the effectiveness of nal-IRI plus 5-FU/LV.

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Efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin after progression on conventional irinotecan-containing chemotherapy for metastatic pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.382 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 382-382

Author(s):

Kyunghye Bang ◽

Jaekyung Cheon ◽

Jae Ho Jeong ◽

Hyeon-Su Im ◽

Kyu-Pyo Kim ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Cumulative Dose ◽

Negative Correlation ◽

Objective Response ◽

Metastatic Pancreatic Adenocarcinoma ◽

Common Grade ◽

Previously Treated ◽

Liposomal Irinotecan ◽

Grade 3 ◽

Median Cumulative Dose

382 Background: Liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has demonstrated its clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on prior gemcitabine-based chemotherapy. However, its role in patients who previously treated with conventional irinotecan has not been investigated. We analyzed clinical outcomes of nal-IRI + 5-FU/LV in mPAC patients after progression on conventional irinotecan-containing chemotherapy. Methods: In this multicenter retrospective analysis, a total of 35 patients with mPAC who received nal-IRI + 5-FU/LV after progression on irinotecan-containing regimen, between January 2017 and March 2020, were included. The ratio of time-to-progression (TTP) with nal-IRI + 5-FU/LV to TTP with conventional irinotecan (TTPr) was correlated with duration and cumulative dose of prior conventional irinotecan. Results: The median age was 58 years (range, 35-73) and 16 patients (46%) were male. All patients received prior irinotecan as the component of FOLFIRINOX. The median duration of prior irinotecan was 4.6 months (range, 0.5-16.8) and median cumulative dose of prior irinotecan was 1230 mg (range, 150-4650). Objective response rate of nal-IRI + 5-FU/LV was 2.9% (1 partial response) and stable disease was achieved in 31.4% (n = 11). With median follow-up duration of 9.2 months [95% CI, 7.8-10.5], the median PFS and OS were 2.0 months [95% CI, 1.4-2.6] and 4.4 months [95% CI, 3.6-5.7], respectively. 6-month PFS rate was 16.3% and OS rate was 37.5%. The median TTPr was 0.41 (range 0.07-2.07) and this showed negative correlation between cumulative dose of prior irinotecan (R = -0.37, p = 0.041). There was a tendency for the negative correlation between TTPr and duration of prior irinotecan (R = -0.35, p = 0.062). Most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%). Conclusions: Nal-IRI + 5-FU/LV showed only modest efficacy for mPAC patients who progressed on conventional irinotecan-containing chemotherapy. Cumulative dose of prior conventional irinotecan may be correlated with the efficacy of nal-IRI + 5-FU/LV.

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Metastatic pancreatic adenocarcinoma treated with liposomal irinotecan in combination with 5-fluorouracil and leucovorin as a II line chemotherapy

Oncoreview ◽

10.24292/01.or.122270621 ◽

2021 ◽

Vol 11 (2(42)) ◽

pp. 44-47

Author(s):

Leszek Kraj ◽

Maciej Gryziak ◽

Ewa Żurawińska-Grzelka ◽

Krzysztof Woźniak

Keyword(s):

Pancreatic Tumor ◽

Treatment Options ◽

Stage Iv ◽

Progression Free Survival ◽

Free Survival ◽

Metastatic Pancreatic Adenocarcinoma ◽

Stage Iv Disease ◽

Liposomal Irinotecan ◽

New Treatment ◽

Better Than

The paper presents a case of a 54-year-old man with pancreatic tumor and intraperitoneal dissemination. The patient received treatment with gemcitabine in combination with nab-paclitaxel. After 18 months, the disease progressed, therefore the line of treatment was applied in the form of liposomal irinotecan with 5-FU/LV. This therapy provided progression-free survival for 7 months. The obtained results are better than the median progression-free survival obtained in the studies. This case demonstrates that liposomal irinotecan in the treatment of stage IV disease in patients progressing after gemcitabine opens up new treatment options.

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Treatment Options for Germline BRCA-Mutated Metastatic Pancreatic Adenocarcinoma

Journal of the Advanced Practitioner in Oncology ◽

10.6004/jadpro.2021.12.5.4 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Doreen Grzelak, NP-C, AOCN, AGN-BC

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Parp Inhibitor ◽

Treatment Options ◽

Pathogenic Variants ◽

Metastatic Pancreatic Adenocarcinoma ◽

Free Treatment ◽

Advanced Practitioner ◽

Platinum Based Chemotherapy ◽

Cancer Network

Pancreatic cancer is the fourth leading cause of death from cancer in both men and women. Pancreatic cancer is typically diagnosed at an advanced stage and has an overall 5-year survival of approximately 9.3%. The National Comprehensive Cancer Network recommends both germline testing (testing cells such as blood or skin that do not have cancer) as well as somatic testing (testing cells with cancer) for pathogenic variants that may increase the risk of pancreatic cancer. In December 2019, the U.S. Food & Drug Administration approved the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib for maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma in individuals who have completed at least 16 weeks of progression-free treatment with first-line platinum-based chemotherapy. This new therapy option has implications not only for treatment but also for the role of the oncology advanced practitioner as genetic testing becomes more prevalent in the care of patients with cancer.

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