Gemcitabine Plus Nab-paclitaxel Research Articles

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer

Background/objectivesLiposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. MethodsIn total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. ResultsThe baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). ConclusionsThe efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Effect of cancer cachexia on first-line chemotherapy in patients with advanced pancreatic cancer: a claims database study in Japan

BackgroundCancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood.MethodsThis is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment.ResultsA total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94–146) in the cachexia group and 143 days (95% CI 134–152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979–1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP.ConclusionCancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment.Clinical Trial Registration clinicaltrials.jp: UMIN000045820.

FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel as First Line Treatment in Pancreatic Cancer: A Real-World Comparison.

Advanced pancreatic cancer has a poor prognosis and a 5-year survival rate <5%; thus, treatment of patients with advanced unresectable or metastatic disease is challenging. Current guidelines recommend either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FOL) as first-line treatment. Data on both efficacy and toxicity of FOL versus GnP in metastatic cancer are limited. This study aimed to compare the two chemotherapy regimens in terms of efficacy and toxicity in a real-world setting. This retrospective propensity score matching study reviewed the medical records of 123 consecutive patients with advanced or metastatic pancreatic cancer who received either GnP or FOL between March 2013 and January 2019 in Guglielmo da Saliceto Hospital, Piacenza. Fifty patients (40.65%) received FOL, administered in an attenuated dose, and seventy-three patients (59.35%) received GnP. After a propensity matching score, 100 patients were retrospectively evaluated. In the final matched cohort, there was no difference in neoadjuvant therapy, radiotherapy, and surgery performed before the first-line therapy between the two groups. Progression-free survival and overall survival were comparable between the two groups and no difference was found in the percentage of toxicity. There was no difference in outcomes between patients who received FOL and those who received GnP. Unexpectedly, no greater FOL-related toxicity was found, probably due to the dose reduction.

Biweekly gemcitabine plus nab-paclitaxel as first-line therapy for older adult patients with unresectable pancreatic cancer: A prospective study.

672 Background: Although the number of older adult patients (aged ≥ 75 years) with pancreatic cancer (PC) is increasing, there are still limited data regarding chemotherapy for these patients, who experience adverse events more frequently than younger patients with PC. In this study, we evaluated the efficacy and safety of biweekly gemcitabine plus nab-paclitaxel (GnP) as first-line therapy for older adult patients with unresectable PC. Methods: We conducted a single-center prospective study. Patients aged ≥ 75 years with pathologically proven unresectable pancreatic adenocarcinoma were enrolled after obtaining written informed consent. Patients were treated with a modified regimen of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 15 of every 28-day cycle. The primary endpoint was the overall response rate. Secondary endpoints included disease control rate, overall survival, progression-free survival, 1-year survival rate, 2-year survival rate, and adverse events. Results: From August 2018 to March 2021, 17 patients were enrolled (locally advanced 4; metastatic 13). Five patients (29.4%) were men, and the median age was 77 years (range: 75-81). The median Geriatric 8 score was 13 points (range 6-17). Biliary drainage was performed in three patients. The overall response rate was 47.1% (8/17). Disease control rate was 82.4% (14/17). Median overall survival was 16.8 months (95% confidence interval (CI) 5.9-24.6) and median progression-free survival was 8.3 months (95% CI: 4.9-10.1), respectively. The 1-year survival rate and 2-year survival rates were 58.8% and 29.4%, respectively. Grade 3 or 4 hematologic adverse events and non-hematologic adverse events were observed in 17.6% (3/17) and 29.4% (5/17), respectively. No deaths was observed in association with biweekly GnP regimen. Conclusions: Biweekly GnP as first-line therapy can provide favorable treatment outcomes with tolerable toxicity in older adult patients with unresectable PC. Clinical trial information: jRCTs051190038 .

Abstract C068: Construction of preclinical study model for optimal anticancer drug selection using PDX model in pancreatic cancer

Abstract Background: Translational research using the patient-derived xenograft (PDX) model is progressing rapidly and is also becoming widespread in pancreatic cancer research. Since PDX models retain the characteristics and the heterogeneity of the primary tumor, PDX models can be reflected in the effectiveness of the anticancer drug in human. The purpose of this study was to establish the PDX library of pancreatic cancer for preclinical study. Methods: The tissues of the pancreatic cancer were obtained from patients who underwent surgery at our hospital. Two PDX models were established using immunodeficient rats. One case was effective in gemcitabine plus nab-paclitaxel (GnP) therapy, and the other was ineffective in GnP therapy in preoperative treatment. 5-FU, CPT-11, L-OHP, GEM, and CDDP were administered to these PDX models once a week for 3 weeks. The primary endpoint was tumor shrinkage. Results: GEM was effective in PDX model in a case in which GnP therapy was effective in the clinical setting, in contrast, GEM was ineffective in PDX model in a case in which GnP was ineffective in the clinical setting. This result was correlated with actual clinical practice. Conclusions: In this study, single anticancer drug tests were performed on PDX models using immunodeficient rats. The efficacy of anticancer drugs was correlated with the clinical setting, indicating that our PDX models might be useful as a preclinical study model. We are currently conducting multi anticancer drug studies. Citation Format: Ryota Tanaka, Kenjiro Kimura, Naoki Tani, Shimpei Eguchi, Ken Kageyama, Shuhei Kushiyama, Shigeaki Kurihara, Masahiko Kinoshita, Kohei Nishio, Hiroji Shinkawa, Go Ohira, Akira Yamamoto, Takeaki Ishizawa. Construction of preclinical study model for optimal anticancer drug selection using PDX model in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C068.

Genomic profile and clinical features of MSI-H and TMB-high pancreatic cancers: real-world data from C-CAT database.

Microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-high) pancreatic cancer are rare, and information is lacking. Based on the C-CAT database, we analyzed the clinical and genomic characteristics of patients with these subtypes. We retrospectively reviewed data on 2206 patients with unresectable pancreatic adenocarcinoma enrolled in C-CAT between July 2019 and January 2022. The clinical features, proportion of genomic variants classified as oncogenic/pathogenic in C-CAT, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) of chemotherapy as first-line treatment were evaluated. Numbers of patients with MSI-H and TMB-high were 7 (0.3%) and 39 (1.8%), respectively. All MSI-H patients were TMB-high. MSI-H and TMB-high patients harbored more mismatch repair genes, such as MSH2, homologous recombination-related genes, such as ATR and BRCA2, and other genes including BRAF, KMT2D, and SMARCA4. None of the 6 MSI-H patients who received chemotherapy achieved a clinical response, including 4 patients treated with gemcitabine plus nab-paclitaxel (GnP) therapy, whose DCR was significantly lower than that of microsatellite stable (MSS) patients (0 vs. 67.0%, respectively, p = 0.01). Among the TMB-high and TMB-low groups, no significant differences were shown in ORR, DCR (17.1 vs. 23.1% and 57.1 vs. 63.1%, respectively), or median TTF (25.9 vs. 28.0weeks, respectively) of overall first-line chemotherapy. MSI-H and TMB-high pancreatic cancers showed some distinct genomic and clinical features from our real-world data. These results suggest the importance of adapting optimal treatment strategies according to the genomic alterations.

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27–0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58–1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

S49 A Systematic Review and Meta-Analysis of Folfirinox (FFX) vs Gemcitabine Plus Nab-Paclitaxel (GnP) as the Initial Treatment for Pancreatic Cancer (PC)

S49 A Systematic Review and Meta-Analysis of Folfirinox (FFX) vs Gemcitabine Plus Nab-Paclitaxel (GnP) as the Initial Treatment for Pancreatic Cancer (PC)

Initial chemotherapy option for pancreatic ductal adenocarcinoma in patients with adequate performance status

Pancreatic ductal adenocarcinoma (PDAC) is a highly progressive lethal malignancy, with chemotherapy being the primary treatment modality. This article provides a review of the initial chemotherapy options for PDAC patients with adequate performance status, comparing FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) or modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NabP) regimens. The availability of limited evidence from randomized trials restricts a direct comparison between the 2 regimens. Based on our review, (m)FOLFIRINOX yields superior survival outcomes compared to GEM-NabP in metastatic PDAC. For locally advanced PDAC, either (m)FOLFIRINOX or GEM-NabP can be considered initial chemotherapy. In the neoadjuvant setting for borderline resectable PDAC, both regimens have demonstrated promising results in achieving feasible resection rates. However, mFOLFIRINOX remains the preferred choice for adjuvant chemotherapy. The selection of initial chemotherapy for PDAC depends on the disease stage, patients’ performance status, and tumor molecular alterations. Further research and clinical trials are necessary to optimize treatment approaches for PDAC patients.

Low-dose gemcitabine plus nab-paclitaxel versus standard-dose gemcitabine plus nab-paclitaxel in elderly patients with metastatic pancreatic cancer: A randomized Phase II trial.

A multicenter, open-label randomized Phase II trial was conducted to determine whether low-dose gemcitabine plus nab-paclitaxel (GnP) could improve tolerability and show equivalent efficacy to the standard-dose GnP for elderly patients with metastatic pancreatic cancer. Consecutive patients aged ≥65 years with metastatic pancreatic cancer who presented at one of four Japanese referral centers between November 2016 and January 2021 were enrolled. The 60 patients were randomly assigned to low- or standard-dose groups with a 1:1 ratio. Patients in the low-dose GnP group received gemcitabine at a dose of 250 mg/m2 and nab-paclitaxel at 125 mg/m2. Low-dose GnP significantly decreased the rate of cases requiring dose reduction (16.7% vs 63.3%). The response rate (36.7% vs 33.3%) and progression-free survival (7.3 vs 8 months) were comparable between the low- and standard-dose groups as determined by independent review. The difference in the median overall survival between the two groups was not significant (7.9 vs 12 months). The proportion of patients with hematologic and non-hematologic treatment-related adverse events was comparable between the two groups. Low-dose GnP had an equivalent efficacy to conventional therapy; however, it did not reduce adverse events.

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma.

Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC. Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated. A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049). As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel

BackgroundThe purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. MethodsFrom 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. ResultsForty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). ConclusionsIn BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

Phase 2 study of elraglusib (9-ING-41), a glycogen synthase kinase-3b inhibitor, in combination with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDAC).

e16289 Background: Despite the increasing incidence and low survival rates in PDAC, treatment options remain somewhat limited. Glycogen synthase kinase-3 (GSK-3) has been known to regulate tumor cell survival and proliferation, suppress apoptosis, and counteract chemotherapy resistance through activation of NF-kB-dependent gene transcription. Elraglusib (9-ING-41), a potent small molecule inhibitor of GSK-3β, has demonstrated inhibition of tumor growth and regression of tumors in patient-derived PDAC xenograft models in combination with gemcitabine (G). This provides the rationale for evaluating the efficacy and safety of elraglusib in combination with GnP in advanced PDAC. Methods: In an open-label, non-randomized, phase 2 study (NCT03678883), pts with previously untreated advanced PDAC received elraglusib 15 mg/kg IV on Days 1 and 4 of each week and nab-paclitaxel (nP) 125 mg/m2 plus G 1000 mg/m2 on Days 1, 8, and 15 in a 28-day cycle. Based on the Simon’s 2-stage design, if &gt; 50% of the first 23 efficacy evaluable (EE) pts achieved a disease control rate (DCR) ≥16 weeks in Stage 1, an additional 37 pts would be enrolled during Stage 2. The primary endpoint was DCR, defined as stable disease for ≥16 weeks, confirmed complete response, or confirmed partial response. Secondary endpoints consisted of objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs). Results: 42 pts (ITT) with ECOG 0 to 2 were enrolled in the study (38 received elraglusib at 15 mg/kg and 4 at 9.3 mg/kg); 29 pts with complete first post-baseline tumor assessment comprised the EE population. The median duration of treatment (as of February 4, 2023, cutoff) in the EE was 5.5 months. The DCR was 51.7% (95% CI, 32.5 to 70.6), and the ORR was 37.9% (95% CI, 20.7 to 57.7). Given that Stage 1 criterium of Simon’s 2-stage design was met, the study proceeded to Stage 2. The median PFS and OS were 4.9 months (95% CI, 4.1 to 7.5) and 15.8 months (95% CI, 7.9 to not estimable), respectively, in the EE and 4.9 months (95% CI, 4.1 to 7.5) and 13.7 months (95% CI, 7.9 to 18.1) in the ITT. Grade ≥3 TEAEs occurred in 85.7% of pts in the ITT population. Two pts (4.8%) developed grade ≥3 reversible visible disturbances related to elraglusib and 8 pts (19%) developed grade ≥3 TEAEs (most common being febrile neutropenia and anemia) related to the combination of elraglusib with GnP. All of these were observed at the highest dose of elraglusib (15 mg/kg). Conclusions: Elraglusib in combination with GnP demonstrates early evidence of clinical activity against advanced PDAC and an acceptable safety profile. The study has advanced to randomized phase 2 in pts with metastatic PDAC evaluating the 9.3 mg/kg dose of elraglusib plus GnP compared to GnP alone. Clinical trial information: NCT03678883 .

Conversion Surgery for Unresectable Pancreatic Cancer Treated With FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel.

Recent advances in chemotherapy have made significant progress in conversion surgery (CS) for unresectable pancreatic cancer (uPC). However, the success rate and efficacy of CS have not been fully demonstrated in patients with uPC treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP). We retrospectively reviewed the records of 318 patients with uPC who received FFX or GnP as first-line chemotherapy. The efficacy in the CS group, defined as undergoing complete resection after chemotherapy, was analyzed, and compared with the non-CS group; then, contributing factors to achieving CS were extracted. We also analyzed differences in the efficacy of CS between locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). Overall, CS was achieved in 4.3% of cases, eight patients (13.3%) with LAPC and five (2.1%) with MPC. Contributing factors to CS were LAPC, no liver metastasis, CA19-9 ≤37, and chemotherapy response. After adjusting for these, overall survival was significantly better in the CS group than in the non-CS group [median of 32.9 vs. 11.3 months; adjusted hazard ratio (HR)=0.32; 95% confidence interval (CI)=0.14-0.70; p<0.01]. Median relapse-free survival duration after CS was 19.1 and 18.1 months in the LAPC-CS and MPC-CS group, respectively (p=0.84). The median post-conversion survival was 27.6 months in the entire CS group, 43.8 months in the LAPC-CS group and 21.3 months in the MPC-CS group. CS was achieved in 13.3% of LAPC and 2.1% of MPC cases. If possible, CS can markedly improve prognosis, even in MPC.

Comparative Effectiveness of FOLFIRINOX Versus Gemcitabine and Nab-paclitaxel in Initially Unresectable Locally Advanced Pancreatic Cancer: A Population-based Study to Assess Subsequent Surgical Resection and Overall Survival

AimsFirst-line FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan, and OXaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have been publicly funded for patients with unresectable locally advanced pancreatic cancer (uLAPC) in Ontario, Canada. We examined the overall survival and surgical resection rate after first-line FOLFIRINOX or GnP and determined the association between resection and overall survival in patients with uLAPC. Materials and methodsWe conducted a retrospective population-based study including patients with uLAPC who received first-line treatment FOLFIRINOX or GnP from April 2015 to March 2019. The cohort was linked to administrative databases to ascertain demographic and clinical characteristics. Propensity score methods were used to balance differences between FOLFIRINOX and GnP. The Kaplan–Meier method was used to calculate overall survival. Cox regression was used to determine the association between receipt of treatment and overall survival, adjusting for time-dependent surgical resections. ResultsWe identified 723 patients with uLAPC (mean age = 65.8, 43.5% female) who received FOLFIRINOX (55.2%) or GnP (44.8%). The median overall survival and 1-year overall survival probability were higher for FOLFIRINOX (13.7 months, 54.6%) than for GnP (8.7 months, 34.0%). Post-chemotherapy surgical resection occurred in 89 (12.3%) patients (FOLFIRINOX: 74 [18.5%] versus GnP: 15 [4.6%]), with no difference in survival since surgery between FOLFIRINOX and GnP (P = 0.29). After adjusting time-dependent post-treatment surgical resection, FOLFIRINOX (inverse probability treatment weighting hazard ratio 0.72, 95% confidence interval 0.61, 0.84) was independently associated with improved overall survival. ConclusionsIn this real-world population-based study of patients with uLAPC, FOLFIRINOX was associated with improved survival and higher resection rates. FOLFIRINOX was associated with improved survival in patients with uLAPC after accounting for the effect of post-chemotherapy surgical resection, suggesting the benefit of FOLFIRINOX was not solely due to improving resectability.

Prognostic impact of osteosarcopenia in patients with advanced pancreatic cancer receiving gemcitabine plus nab-paclitaxel

BackgroundOsteosarcopenia, defined as the combination of osteoporosis and sarcopenia, has recently gained attention as a novel prognostic factor for survival in patients with cancer. This study aimed to evaluate the prognostic impact of osteosarcopenia in metastatic pancreatic cancer (PC). MethodsWe retrospectively investigated consecutive metastatic PC patients receiving first-line gemcitabine plus nab-paclitaxel (GnP). Skeletal muscle index at the third lumbar vertebra and bone mineral density at the first lumbar vertebra were measured using pretreatment computed tomography. Treatment outcomes of osteosarcopenia and non-osteosarcopenia groups were compared and analyzed. Multivariate analysis was performed to identify variables associated with survival. ResultsAmong 313 patients, osteosarcopenia was present in 59 patients (19%). The osteosarcopenia group was associated with older age, higher proportion of females, worse performance status, and higher modified Glasgow prognostic scores (mGPS). Response rates to chemotherapy, progression-free survival (3.5 months vs. 6.4 months, p < 0.001), and overall survival (5.6 months vs. 13.0 months, p < 0.001) were significantly better in the non-osteosarcopenia group. Osteosarcopenia, performance status of 1–2, mGPS score of 1–2, carcinoembryonic antigen ≥10 ng/mL, and carbohydrate antigen 19-9 ≥ 1000 IU/mL were identified as independent factors predicting shorter survival. Grade 3 or higher anemia and febrile neutropenia occurred more frequently in the osteosarcopenia group. ConclusionsOsteosarcopenia was associated with poor survival in metastatic PC treated with first-line GnP. Screening for osteosarcopenia may be helpful for better management of metastatic PC.

Outcomes of FOLFIRINOX and gemcitabine plus nab-paclitaxel in patients with early recurrent pancreatic cancer after adjuvant S-1: A propensity score–matching analysis.

707 Background: An oral fluoropyrimidine, S-1, is a standard adjuvant (adj) chemotherapy practice in Japan for patients (pts) with resected pancreatic cancer (PC). Patients experiencing recurrence after adj S-1 administration are treated with FOLFIRINOX (FFX), including intravenous fluoropyrimidine, or gemcitabine plus nab-paclitaxel (GN), which is commonly used as the first-line chemotherapy approach in pts with advanced PC. Some pts have good response to FFX with acceptable toxicity levels even though recurrence within 6 months (mo) after the last S-1 administration is attributed to PC refractory to fluoropyrimidine. To the best of our knowledge, there is no clinical study comparing FFX and GN in this particular population. Methods: This multi-center, retrospective study included pts with PC that had a recurrence-free interval (RFI) &lt; 6 mo from the last adj S-1 administration and were treated with FFX or GN between December 2013 and 2018. The decision to administer FFX or GN was taken by the attending physicians. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response, and serious adverse events (SAE). The OS and PFS were calculated from the time of initiation of treatment with FFX or GN. To adjust confounding factors in the comparison of FFX with GN, propensity score-matching (PSM) analysis was performed. Potentially confounding factors were identified by univariate analysis for OS, and statistical significance was set at p &lt; 0.1. Results: A total of 284 (FFX; 50, GN; 234) pts were enrolled from 32 institutions in Japan. Potential confounding factors comprised curability, pathological T/N, tumor differentiation status, reasons for the end of S-1 administration, chemotherapy regimen, performance status, serum albumin/C-reactive protein/carbohydrate antigen 19-9 levels, and presence or absence of liver metastasis before initiating the administration of FFX or GN. After PSM, 43 pts each in the FFX and GN groups were compared in pairs. The patient characteristics, excluding age, in the matched pair were well-balanced; the proportion of pts aged &lt; 65 years in the FFX and GN groups was 61% and 30%, respectively. The median OS and PFS were longer in the GN group than in the FFX group; OS was 14.5 vs. 11.1 mo (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.38-0.97); PFS was 7.1 vs. 5.1 mo (HR, 0.65; 95% CI, 0.41-1.02). The objective response, disease control rates, and observed SAE in the GN and FFX groups were 20/19%, 80/66%, and 14/19% respectively. Seventy-two percent of the pts in the GN group received subsequent therapies of FFX/S-1/FOLFIRI/FOLFOX (28/12/9/5%); while 77% of the FFX group pts received subsequent therapies of GN/GEM (54/7%). Conclusions: Real world data suggests that GN may be recommended in PC pts with RFI &lt; 6 mo from the last administration of adj S-1.

Depth of response in patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory subgroup analysis of JCOG1407.

746 Background: Depth of response (DpR; max% reduction from baseline in sum of target lesion diameters), has been reported to be associated with improved prognosis in several malignancies. However, there have been few reports regarding DpR in patients with locally advanced pancreatic cancer (LAPC). Thus, we investigated the association between DpR and overall survival (OS), and whether there were any differences in treatment efficacy on DpR between modified FOLFIRINOX (mFFX) versus gemcitabine plus nab-paclitaxel (GnP) as 1st-line chemotherapy for LAPC, using the results from JCOG1407 which was a randomized phase II trial comparing these regimens. Methods: Of the 126 patients enrolled in JCOG1407, patients were eligible except for the followings; patients who never had an imaging study or had only non-target lesions. The association between DpR and OS was investigated by dividing DpR into 3 groups at the tertile point (T1, T2 and T3 from largest to smallest), and whether DpR contributes to OS was examined by multivariable analysis. The differences in treatment efficacy between both regimens were investigated byevaluating DpR, time to DpR, and duration of response (DoR). Results: A total of 109 patients were eligible for this study (n = 53/56 in mFFX/GnP). The number of patients in T1, T2, and T3 were 37, 36, and 36, respectively. The median OS of T1, T2, and T3 were 29.3 (95% CI, 21.0-NE), 20.6 (95% CI, 15.8-24.5), and 19.0 months (95% CI, 12.7-22.4), respectively ( P= 0.0237). Multivariable analysis identified DpR as an independent prognostic factor for OS (HR 1.883, 95% CI 1.030-3.442, P= 0.040 for T2 vs. T1, and HR 2.523, 95% CI 1.342-4.744, P= 0.004 for T3 vs. T1). The median DpR in GnP was better than that in mFFX (28.9 vs. 22.7%; P= 0.041). The median DoR in mFFX tended to be longer compared to that in GnP (8.2 vs. 5.3 months; P= 0.132). No differences in mean time to DpR were observed between the two regimens. Conclusions: In LAPC patients receiving 1st-line chemotherapy, larger DpR contributed to OS. Although OS and PFS between mFFX and GnP were similar, the treatment efficacy on DpR and DoR might be different between the two regimens. Clinical trial information: UMIN000023143 .

Efficacy of the third-line chemotherapy in patients with advanced pancreatic cancer.

711 Background: First-line FOLFIRINOX or gemcitabine plus nab-paclitaxel (GNP) have improved the survival outcomes of patients with advanced pancreatic cancer (APC) and nano-liposomal irinotecan (nal-IRI) plus 5-FU/leucovorin is proven as the second-line agents. The current study aims to assess the efficacy of the third-line palliative chemotherapy in APC. Methods: Medical records were retrospectively reviewed in a single tertiary hospital between 2012 and 2020. The enrolled patients have APC who received the first and second-line chemotherapy. To fine the efficacy of the third-line chemotherapy, Kaplan Meier curve with cox-regression analysis was performed. Results: Of total 1,152 patients with pancreatic cancer, 362 patients were enrolled. Of these, 125 received the third-line chemotherapy and 238 received only supportive care after progression of the second-line chemotherapy. Median age at diagnosis was 60.3 years (range 36.0 – 86.0) and males were 52.0%. The first-line chemotherapy regimen was FOLFIRINOX (85, 68.0%), GNP (33, 26.4%), and others (7, 5.6%). The second-line chemotherapy regimen was GNP (55, 44.0%), FOLFIRINOX (34, 27.2%). As the third-line regimen, TS-1 and nal-IRI plus 5-FU/leucovorin were 73 (58.4%) and 20 (16.0%). The median overall survival (OS) from diagnosis was 18.0 months in all patients (95% CI, 14.6 – 21.4). The median OS after progression of the second-line therapy were 15.1 (95% CI, 12.8 – 17.5) and 8.5 weeks (95% CI, 7.7 – 9.4, p=0.007) between the patients with the third-line chemotherapy and supportive care only. Of the patients with the third-line chemotherapy, female showed the significant longer OS than male (12.4 (95% CI 10.2-14.6) vs. 6.6 weeks (95% CI 13.4-19.7), p=0.042). Conclusions: The current study suggested that proceeding with the third-line chemotherapy could be recommended in some patients. Females showed significantly more benefit than males. Further research on the selection for patient who will get the benefit from the third-line therapy is necessary.