The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients: A Multicenter Real-Life Study

Abstract Purpose: To compare the efficacy and toxicity of three different chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer (mPC). Methods: A total of 218 patients diagnosed with mPC at the time of initial admission were included in this multicenter study. Gemcitabine (Gem, n=71), Gemcitabine-cisplatin (Gem-Cis, n=91) and FOLFIRINOX (FFX, n=56) treatments were compared in terms of efficacy and treatment-related toxicity. Results: Overall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (p=0.010).Median progression-free survival (8.4 vs. 4.6 and 5.5 months, respectively, p<0.001) and overall survival (16.4 vs. 8.1 and 8.7 months, respectively, p=0.002) were significantly longer in theFFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46(64.8%), 56(61.5%) and 49(87.5%) patients in the Gem, Gem-Cis and FFX groups, respectively (p=0.003).Of the grade 3-4 toxicities, weakness/fatigue and mucositis were reported only in the FFX group (5.4% and 3.6%, respectively). Grade 3-4 diarrhea (10.7%, 0.0%, 2.2%, respectively) and neutropenia (25%, 4.2% and 5.5%, respectively) were more common in the FFX group than in the Gem and Gem-Cis groups. Conclusion: In conclusion, our findings indicate that FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.FFX seems to be a preferable regimen in the first-line treatment of the younger and fit patients diagnosed with mPC.

Download Full-text

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

Scientific Reports ◽

10.1038/s41598-020-76465-9 ◽

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.

Download Full-text

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis

Cancers ◽

10.3390/cancers11040484 ◽

2019 ◽

Vol 11 (4) ◽

pp. 484 ◽

Cited By ~ 18

Author(s):

Sara Pusceddu ◽

Michele Ghidini ◽

Martina Torchio ◽

Francesca Corti ◽

Gianluca Tomasello ◽

...

Keyword(s):

Pancreatic Cancer ◽

Febrile Neutropenia ◽

Meta Analysis ◽

Real Life ◽

Metastatic Pancreatic Cancer ◽

Cochrane Library ◽

First Line ◽

Risk Of Death ◽

Grade 3 ◽

Line Setting

Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or metastatic pancreatic cancer (mPC). However, no randomized trials comparing the two schemes have been performed. This meta-analysis aims to compare GEM-NAB and FOLFIRINOX in terms of safety and effectiveness, taking into account data from real-life studies on mPC. We systematically searched PubMed, EMBASE and Cochrane library up to November 2018 to identify retrospective or cohort studies on mPC comparing GEM-NAB and FOLFIRINOX. We included 16 retrospective studies, including 3813 patients (2123 treated with GEM-NAB and 1690 treated with FOLFIRINOX). Despite a median weighted overall survival (OS) difference in favor of FOLFIRINOX (mean difference: 1.15, 95% confidence interval CI 0.08–2.22, p = 0.03), in whole population OS was similar (hazard ratio (HR = 0.99, 95% CI 0.84–1.16; p = 0.9). PFS was also not different between the two arms (HR = 0.88, 95% CI 0.71–1.1; p = 0.26). The overall response rate was similar (25 vs. 24% with GEM-NAB and FOLFIRINOX). Among grade 3–4 toxicities, neutropenia, febrile neutropenia, and nausea were lower with GEM-NAB, while neurotoxicity and anemia were lower with FOLFIRINOX. In conclusion, despite a numerically longer median OS with FOLFIRINOX as compared to GEM-NAB, the overall risk of death and progression were similar. Their toxicity was different with less nausea, neutropenia, and febrile neutropenia with GEM-NAB, as compared to less neurotoxicity and anemia with FOLFIRINOX. Therefore, analysis of non-randomized “real world” studies to date has not provided evidence of a major benefit of one regimen over the other.

Download Full-text

Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽

10.3390/cancers11070939 ◽

2019 ◽

Vol 11 (7) ◽

pp. 939 ◽

Cited By ~ 1

Author(s):

Caterina Vivaldi ◽

Lorenzo Fornaro ◽

Carla Cappelli ◽

Irene Pecora ◽

Silvia Catanese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Tumor Shrinkage ◽

First Line ◽

Free Survival ◽

Depth Of Response ◽

Early Tumor Shrinkage ◽

Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

Download Full-text

Activity and safety of Nab-FOLFIRI and Nab-FOLFOX as first-line treatment for metastatic pancreatic cancer (phase II NabucCO study).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.351 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 351-351 ◽

Cited By ~ 1

Author(s):

Elisa Giommoni ◽

Evaristo Maiello ◽

Vanja Vaccaro ◽

Ermanno Rondini ◽

Caterina Vivaldi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Dose Finding ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

First Line ◽

Open Label ◽

Grade 3

351 Background: FOLFIRINOX is an approved regimen for metastatic pancreatic cancer (mPC). We performed a modification in FOLFIRINOX schedule, using nab-paclitaxel (nab-p) to obtain two regimens that could be as effective and less toxic than the original triplet. NabucCO study was a randomized phase II trial to assess activity and toxicity of nab-p instead of either oxaliplatin (Nab-FOLFIRI) or irinotecan (Nab-FOLFOX) in first line setting. Previous dose–finding NabucCO study defined that maximum tolerated dose of nab-p with FOLFIRI is 120 mg/m2, and with FOLFOX is 160 mg/m2. Methods: The study was a 1:1 parallel arm, open label, not comparative one to assess overall response rate (ORR) of Nab-FOLFIRI and Nab-FOLFOX as primary end-point. Patients (pts) with PS 0-1, untreated for mPC were randomized to receive leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2, irinotecan 180 mg/m2 plus nab-p 120 mg/m2 (arm A) or leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2 and oxaliplatin 85 mg/m2 iv plus nab-p 160 mg/m2 (arm B) every 2 weeks for up to 12 cycles. Secondary end points were clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS), and safety. Results: From November 2015 to January 2017, 84 pts were treated (42 for each arm). Median age was 60 years (29-65) in arm A and 64 years (47-64) in arm B. The ORR was 31 % for both schedules, with a CBR of 69% and 71%, respectively. At a median follow-up of 11.4 months for arm A and 14.5 months for arm B (censored on august, 31th 2017), 1-year survival is 41% and 50%, respectively. For Nab-FOLFIRI PFS and mOS were 6 months (90% CI: 4.9-8.0) and 13.2 months (90% CI: 8.3-14.8), while in Nab-FOLFOX were 5.6 months (90% CI:4.9-7.2) and 10.8 months (90% CI: 8.4-12.8). Grade ≥3 toxicities in arm A were neutropenia (19%) and febrile neutropenia (12%). In arm B, main grade ≥3 toxicities were neutropenia (29%), fatigue (14%), peripheral neuropathy (7%). No toxic death were registered. Conclusions: Nab-FOLFIRI and Nab–FOLFOX demonstrated a similar activity to FOLFIRINOX, with better safety profile in terms of neutropenia, fatigue and neuropathy. These results could justify a future phase III evaluation. Clinical trial information: NCT02109341.

Download Full-text

A phase Ib trial of IPI-926, a hedgehog pathway inhibitor, plus gemcitabine in patients with metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.213 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 213-213 ◽

Cited By ~ 12

Author(s):

Donald Anthony Richards ◽

Joe Stephenson ◽

Brian M. Wolpin ◽

Carlos Becerra ◽

John Turner Hamm ◽

...

Keyword(s):

Pancreatic Cancer ◽

Single Agent ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Final Report ◽

Double Blind ◽

Free Survival ◽

Phase 1B ◽

Grade 3 ◽

Dose Reductions

213 Background: IPI-926 is a novel, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting smoothened. In preclinical models of pancreatic cancer, repressing activation of the Hh pathway diminishes tumor-associated desmoplasia and improves chemotherapy delivery. Methods: This is the final report of the Phase 1b portion of a Phase 1b/2 trial evaluating the safety and efficacy of IPI-926 plus gemcitabine. Eligible patients (pts) with untreated metastatic pancreatic cancer and ECOG status 0-1 were administered oral IPI-926 daily (QD) for 28-day cycles, in 3 to 6 pt dose cohorts. Gemcitabine (1,000 mg/m2) was administered IV weekly for 3 weeks with 1 week off. DLTs were evaluated during Cycle 1. Results: 16 pts (median age 69 years; range 58-86) were enrolled at IPI-926 doses of 110, 130 or 160 mg QD (single agent MTD). Pts received a median of 5 cycles (1-13). Two pts remain on trial. No IPI-926-related serious AEs have been observed. One DLT of Grade 3 AST increase was observed (130 mg dose cohort) and was asymptomatic; it resolved with dose interruption, and did not recur with dose reduction. The most common AEs occurring were fatigue (75% total, 6% ≥ Grade 3), thrombocytopenia (63%, 25%), anemia (56%, 13%), nausea (50%, 0%), diarrhea (44%, 0%), vomiting (44%, 0%), peripheral edema (44%, 0%), pyrexia (44%, 0%), and AST increase (44%, 13%). Dose reductions of IPI-926 occurred in 3 (19%) pts. Dose reductions of gemcitabine occurred in 11 (69%) pts, primarily for thrombocytopenia (9 pts). One pt (6%) discontinued due to an AE (microangiopathic hemolytic anemia). Five (31%) radiographic partial responses were observed (1/3 at 110 mg, 2/6 at 130 mg, 2/7 at 160 mg). Median progression-free survival is > 7 months. 74% of pts were alive 6 months after study entry. Conclusions: IPI-926 plus gemcitabine is well tolerated in pts with untreated metastatic pancreatic cancer, with evidence of activity and no unexpected toxicity. Complete Phase 1b data, including final overall survival, will be presented. Clinical evaluation of this combination continues in the randomized, double-blind, placebo-controlled Phase 2 portion of the trial.

Download Full-text

Cisplatin, Fluorouracil in Bolus Injection, and Leucovorin in First-Line Therapy for Advanced Gastric Cancer as an Alternative to Protocols With Infusional Fluorouracil

Journal of Global Oncology ◽

10.1200/jgo.18.00176 ◽

2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Rafael C. Coelho ◽

Pedro D.P. Abreu ◽

Mariana R. Monteiro ◽

Ana Paula Stramosk ◽

Alvaro Henrique I. Garces ◽

...

Keyword(s):

Gastric Cancer ◽

Progression Free Survival ◽

Median Number ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Grade 3 ◽

Number Of Cycles ◽

Line Setting ◽

Platinum Agents

PURPOSE Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

Download Full-text

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer

Biomolecules ◽

10.3390/biom11060780 ◽

2021 ◽

Vol 11 (6) ◽

pp. 780

Author(s):

Ilario Giovanni Rapposelli ◽

Andrea Casadei-Gardini ◽

Caterina Vivaldi ◽

Giulia Bartolini ◽

Laura Bernardini ◽

...

Keyword(s):

Pancreatic Cancer ◽

Prospective Trial ◽

Indirect Comparison ◽

Predictive Biomarkers ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

First Line ◽

First Line Therapy ◽

Equivalent Efficacy ◽

Grade 3

FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81–1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82–1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC.

Download Full-text

Randomized Phase II Trial Evaluating Two Sequential Treatments in First Line of Metastatic Pancreatic Cancer: Results of the PANOPTIMOX-PRODIGE 35 Trial

Journal of Clinical Oncology ◽

10.1200/jco.20.03329 ◽

2021 ◽

pp. JCO.20.03329

Author(s):

Laetitia Dahan ◽

Nicolas Williet ◽

Karine Le Malicot ◽

Jean-Marc Phelip ◽

Jérôme Desrame ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Phase Ii ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Free Survival ◽

Dismal Prognosis ◽

Stop And Go ◽

Sequential Treatments ◽

Grade 3

PURPOSE Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4—ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC. METHODS In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months. RESULTS Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively). CONCLUSION Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.

Download Full-text

Results of the VENUS study: Bevacizumab efficacy and safety in platinum-sensitive recurrent ovarian cancer (OC)—A real-life ambispective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5540 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5540-5540

Author(s):

Isabelle Laure Ray-Coquard ◽

Jerome Alexandre ◽

Francois Goldwasser ◽

Jean-Philippe Spano ◽

Dominique Berton-Rigaud ◽

...

Keyword(s):

De Novo ◽

Real Life ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Free Survival ◽

Life Study ◽

Platinum Sensitive ◽

Real Life Setting ◽

Grade 3

5540 Background: The VENUS study reports on the efficacy/safety of bevacizumab (Bev) in patients (pts) treated in the real-life setting. Methods: In this multicentric observational ambispective VENUS study, all Pts were naive of any antiVEGF and received Bev +/- chemotherapy. Pts were followed until progression or death, for a maximum of 3 years since Bev initiation. De novo side effects were defined as symptoms for which patients were naïve at baseline. Results: 148 OC pts were included (27 centres), 10 excluded and 8 were lost of follow-up. 52 were retrospective. Median age 64 years (55-70). 84.1% were advanced. Median duration of Bev was 8.6 months, min 1 max 36 months. Initial Bev dose was 15 mg/kg Q3W for 65.3%, 10.0 for 22.5%, 7.5 for 10.2% and 5.0 for 2%. 2 pts presented with thrombotic micro-angiopathy (1.4%). Before Bev, hypertension (HTN) was present in 28.9%; proteinuria in 11.3%. Incidence of de novo HTN was 25%. 43 pts (31.2%) experienced de novo Grade 1-2 Pu, for a total of 56 events, no grade 3-4 was observed. A total of 12 Grade 4 events occurred: 9 neutropenia and 3 thrombopenia. Mean overall survival (OS) and progression free survival (PFS) were 30.0 and 13.3 months, respectively. Conclusions: 1) 1/3 of pts were treated at low doses in this real-life study; 2) safety of Bev in real-life was manageable and as expected, 3) OS and PFS were consistent with those reported in the OCEANS study: PFS 12.4 and OS 33.6 months but lower than in the GOG-0213 study: PFS 13.8 and OS 42.6 months. De novo events recorded during follow-up. [Table: see text]

Download Full-text

FOLFIRINOX de-escalation in advanced pancreatic cancer (aPC): A multicenter real-life study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4639 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4639-4639

Author(s):

Hortense Chevalier ◽

Angélique Vienot ◽

Astrid Lièvre ◽

Julien Edeline ◽

Farid El Hajbi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Real Life ◽

Progression Free Survival ◽

Median Number ◽

Rank Test ◽

Multicentric Study ◽

Free Survival ◽

Life Study

4639 Background: FOLFIRINOX (5FU, irinotecan, and oxaliplatin) is a reference first line (L1) of chemotherapy (CT) in fit patients (Pts) with advanced pancreatic cancer (aPC). Limiting toxicities (in particular, neuropathy) are frequent and maintaining quality of life without a lack of efficacy is a crucial need. Modalities and efficacy of maintenance strategy in aPC remain scarcely studied. Our study describes the French practices of a FOLFIRINOX de-escalation and maintenance in a real-life multicentric cohort. Methods: We performed a retrospective multicentric study in 5 French centers. Pts receiving FOLFIRINOX L1 for aPC were recruited between January 2011 and December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan in patients without tumor progression, after at least 4 cycles of FOLFIRINOX. Maintenance schedules were oral capecitabine or intravenous (IV) 5FU, FOLFOX or FOLFIRI. Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1) and, in case of reintroduction of FOLFIRINOX, second progression free survival (PFS2). OS and PFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Among the 321 patients included, 147 (46%) received a maintenance therapy. Median age was 60.0 (53-66), 35 (24%) had locally advanced PC and 91 (62%) had metastatic PC. The median number of cycles of FOLFIRINOX was 9.0 (6.0-11.0). Median OS was 16.1 months (95%CI=13.7-20.3). Median PFS1 was 9.4 months (95%CI=8.5-10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%), vs fluoropyrimidine (FP) in 52 (35%) and FOLFOX in 25 (17%). Among 118 Pts who received a maintenance CT with FP or FOLFIRI, there was no difference in PFS1 (median: 10.1 vs 9.0, respectively, p=0.33) or OS (median: 16.6 versus 18.7, p=0.86) between the 2 maintenance regimens. After progression under maintenance CT with FOLFIRI or FP, reintroduction of FOLFIRINOX was performed in 20.2% of Pts, with a median PFS2 of 2.8 months (95%CI=2.0-22.3). The rates of G3-4 toxicity were significantly higher during FOLFIRI maintenance CT than with FP (41% vs 22%, p=0.03), especially neuropathy (73% vs 9%). Conclusions: FOLFIRINOX de-escalation in aPC is largely used in France. Fluoropyrimidine maintenance chemotherapy appears to be as effective as FOLFIRI.

Download Full-text