Efficacy and toxicity of gemcitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma after disease progression on FOLFIRINOX: a single-center analysis

Introduction

Pancreatic cancer remains one of the most lethal human malignancies. It currently represents the 6^th most common cause of cancer-related death worldwide (1), with an increasing epidemiological burden in the decades to come (2). At presentation, half of patients present distant metastases and, for these patients, systemic chemotherapy is the cornerstone of therapy (3). However, despite recent improvements, the median overall survival (mOS) in this setting has consistently been shown to be less than 12 months (4).

FOLFIRINOX is one of the most active chemotherapy regimens in the treatment of metastatic pancreatic adenocarcinoma (MPA). In the pivotal study PRODIGE 4/ACCORD 11, FOLFIRINOX was associated with improved overall response rate (ORR; 31.6% vs. 9.4%; P<0.001), median progression-free survival (mPFS; 6.4 vs. 3.3 months; P<0.001), and mOS (11.1 vs. 6.8 months; P<0.001) when compared to single-agent gemcitabine (5). However, virtually all patients treated with FOLFIRINOX will experience disease progression, mandating a change in the chemotherapy regimen.

Given the activity of gemcitabine plus nab-paclitaxel (GnP) in first-line and the differences in the mechanisms of action between individual components of GnP and FOLFIRINOX (6,7), the use of this combination in second-line is reasonable. Despite the lack of high-quality evidence supporting the use of GnP in this setting, multiple retrospective studies suggest clinically meaningful activity (8-12). Importantly, this combination is likely associated with increased efficacy when compared to single-agent gemcitabine, albeit with increased toxicity (13). However, recent prospective data have challenged the activity of GnP after progression on FOLFIRINOX, and additional information on its efficacy and safety is needed (14). Moreover, Latin American patients have systematically been underrepresented in previous investigations on this subject, highlighting the need to carry out studies in this population.

That said, we sat out to retrospectively evaluate the clinical activity and toxicity pattern of patients treated with GnP in second-line after progression with FOLFIRINOX. We also compared the efficacy and safety outcomes of patients treated with GnP in this cohort with those of patients treated with single-agent gemcitabine in a previous publication from our group. We present this article in accordance with the STROBE reporting checklist (available at https://apc.amegroups.com/article/view/10.21037/apc-25-5/rc).

Methods

Study design

This is a unicentric, descriptive, analytical, and retrospective cohort study assessing the role of GnP in the management of patients with MPA after FOLFIRINOX. We gathered routinely collected data from the electronic medical records of patients with MPA who were diagnosed from January 1^st, 2015 to December 31^st, 2022 and treated with GnP in second-line. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was conducted at A.C. Camargo Cancer Center and was approved by the A.C. Camargo Cancer Center Internal Ethical Review Board (No. CAAE 71605423.4.0000.5432). Due to its retrospective nature, the need for an informed consent was waived.

Population

We included patients aged 18 years old and above with pathologically confirmed diagnosis of pancreatic adenocarcinoma with radiological or pathological confirmation of metastatic disease from January 1^st, 2015 to December 31^st, 2022 who were treated with GnP in second line after progression on FOLFIRINOX in first-line. We excluded patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 3 or more at the start of second-line treatment and those who had treatment changed from FOLFIRINOX to GnP due to treatment intolerance.

Procedures

Patients received either standard or modified GnP. In standard GnP, patients received gemcitabine 1,000 mg/m² and nab-paclitaxel 125 mg/m² on days 1, 8, and 15 every 28 days. In modified GnP, patients received gemcitabine and nab-paclitaxel at the same doses on days 1 and 15 every 28 days. Modifications in the GnP protocol were devised to reduce chemotherapy-associated toxicities. Radiological response evaluation was carried out every 2 to 3 months with abdominal computed tomography (CT) or magnetic resonance imaging and chest CT.

Outcomes

We defined overall survival as the interval between the start of GnP in second-line and death or last visit. Progression-free survival was the interval between the start of GnP and disease progression or death. ORR was defined as the ratio of patients with radiological response and the total number of patients. Disease control rate (DCR) was defined as the ratio of patients with radiological response or stable disease and the total number of patients. Radiological response was assessed using the treating physician’s impression from the medical record or radiology reports [and not with Response Evaluation Criteria in Solid Tumors (RECIST)]. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 (15).

Exploratory analysis

Since the approval of nab-paclitaxel in Brazil, we have shifted to recommend GnP (as opposed to gemcitabine) as the preferred second-line therapy after FOLFIRINOX. Therefore, in recent years few patients were treated with single-agent gemcitabine in this setting. Also, there has been no major improvement in the treatment of pancreatic cancer in third or further lines in the past 10 years. Therefore, to compare the outcomes of patients treated with GnP with those of single-agent gemcitabine, we gathered the data of patients treated with single-agent gemcitabine after disease progression during first-line FOLFIRINOX from a previous publication from our group (16). To improve comparability, we used the same inclusion criteria used in the primary analysis.

Statistical analyses

We used absolute values and ratios to describe the distributions of categorical variables and median values and interquartile ranges (IQRs) to outline the distribution of numerical variables. We compared the distribution of categorical variables between two different groups using Fisher’s exact test and the distribution of numerical variables using the Mann-Whitney U test. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. Median follow-up was calculated using the reverse Kaplan-Meier method. Patients without an event were censored at the last visit. All analyses were based on complete-case approach. We considered two-tailed P values <0.05 as statistically significant. As a retrospective study, no formal analysis of sample size and statistical power was conducted. Statistical analysis was performed with Stata version 18.0.

Results

Study population

From January 2015 to December 2022, we identified 109 patients with pancreatic cancer treated with GnP. Eighty patients were excluded for the following reasons: treatment in first-line setting (N=65), second-line GnP after a first-line regimen other than FOLFIRINOX (N=5), treatment with GnP in third-line (N=4), lack of metastasis at start of GnP (N=4), ECOG 3 at start of GnP (N=1), and change from FOLFIRINOX to GnP due to treatment intolerance (N=1). Therefore, the study population consists of 29 patients (Figure 1).

Figure 1 Study population flowchart. ECOG, Eastern Cooperative Oncology Group; FFX, FOLFIRINOX; GnP, gemcitabine plus nab-paclitaxel; M, metastasis.

Table 1 summarizes the demographical and clinical characteristics of the study population (no missing data). The median age at the start of GnP was 64 years (IQR: 57–68 years), with a slight female predominance (N=15; 51.7%). Most patients presented ECOG performance status 0 or 1 (N=27; 93.1%), with a median Charlson comorbidity score of 8 (IQR: 7–9). The median CA 19-9 level was 614 UI/mL (IQR: 189–6,700 UI/mL). Most patients had hepatic metastasis (N=17; 58.6%), with 48.3% (N=14) of patients presenting a single site of metastatic disease.

Treatment characteristics

Twelve patients (41.4%) received modified GnP. The median number of cycles was 4 (IQR: 2–8) (Table 2). Treatment de-escalation (to single-agent gemcitabine) occurred in 7 patients (24.1%) after a median of 1 cycle (IQR: 1–2.5). The median starting doses of gemcitabine and nab-paclitaxel were 1,000 mg/m² (IQR: 850–1,000 mg/m²) and 125 mg/m² (IQR: 106.25–125 mg/m²), respectively.

Efficacy and toxicity analyses

Median follow-up was 17.9 months [95% confidence interval (CI): 15.0–not applicable (NA)]. mOS was 5.6 months (95% CI: 4.3–12.6) and the mPFS was 3.7 months (95% CI: 2.5–5.3) (Figure 2A,2B). The ORR was 17.2% (N=5) and the DCR was 48.3% (N=14). The most frequent grade 3 or higher toxicities for patients treated with GnP were anemia (N=6; 21.4%) and thrombocytopenia (N=8; 27.6%) (Table 3).

Figure 2 Overall survival (A) and progression-free survival (B) of patients treated with GnP. GnP, gemcitabine plus nab-paclitaxel.

Exploratory analysis

Figure S1 describes the composition of the single-agent gemcitabine population and Table S1 describes the demographical and clinical characteristics of patients treated with GnP and single-agent gemcitabine. More patients treated with single-agent gemcitabine had an ECOG performance status of 2 (6.9% vs. 30.8%; P=0.003). The median number of chemotherapy cycles was 4 (IQR: 2–9) in the GnP arm and 2 (IQR: 2–3) in the single-agent gemcitabine arm (P=0.08).

There was no difference in the median follow-up between the two study arms (17.9 vs. 20.6 months; P=0.62). Figure 3A,3B describes the overall survival and progression-free survival curves. The mOS was 5.6 months (95% CI: 4.3–12.6) in the GnP arm and 4.5 months (95% CI: 3.3–7.7) in the single-agent gemcitabine arm (P=0.11). The mPFS was 3.7 months (95% CI: 2.5–5.3) in the GnP arm and 2.3 months (95% CI: 1.9–2.7) in the single-agent gemcitabine arm (P=0.007). The ORR was numerically higher in patients treated with GnP (17.2% vs. 0.0%; P=0.05). Likewise, the DCR was numerically higher in patients treated with GnP (48.3% vs. 23.1%; P=0.10) (Table S2).

Figure 3 Overall survival (A) and progression-free survival (B) of patients treated with GnP or single-agent gemcitabine. GnP, gemcitabine plus nab-paclitaxel.

Treatment with GnP was associated with an increased risk of grade 3 or higher anemia (21.4% vs. 0.0%; P=0.02). Additionally, there was a numerical increase in the incidence of grade 3 or higher thrombocytopenia in patients treated with GnP (27.6% vs. 12.0%; P=0.19) (Table S3).

Discussion

In this study, we show that GnP can be safely used in the second-line setting after progression on FOLFIRINOX. Also, compared to the historical control of patients treated with single-agent gemcitabine, treatment with GnP was associated with improved progression-free survival and numerically higher overall survival.

For patients with MPA who experience treatment failure with FOLFIRINOX in first-line, there is little data to guide treatment decisions. The only study comparing two different regimens of chemotherapy in this setting is the GEMPAX/PRODIGE65 (17). In this randomized controlled trial, 211 patients with MPA who received FOLFIRINOX in first-line were randomized to receive single-agent gemcitabine (1,000 mg/m² on days 1, 8, and 15 every 28 days) or gemcitabine plus paclitaxel (80 mg/m² on days 1, 8, and 15 every 28 days). Despite the improvements in ORR (17.1% vs. 4.2%; P=0.008) and mPFS (3.1 vs. 2.0 months; P=0.007), the study failed to demonstrate improvements in mOS (6.4 vs. 5.9 months; P=0.41). It is important to highlight that nab-paclitaxel has the potential advantage over solvent-based paclitaxel as it exploits albumin to carry paclitaxel directly into cancer cells through a receptor-utilized carrier system, improving the penetration of the drug in the tumor tissue (18). Indeed, despite the dearth of data on the activity of single-agent solvent-based paclitaxel in MPA (19), in many tumor types nab-paclitaxel has been associated with improved treatment outcomes when compared to solvent-based paclitaxel (20-23).

Given the role of the GnP regimen in first-line and the differences in the mechanism of action between the drugs included in this regimen and in FOLFIRINOX, the use of GnP in second-line seems sound. In our study, we identified an ORR of 17.2% and a DCR of 48.3%. Also, mOS and mPFS were 5.6 and 3.7 months, respectively. These results are in line with the findings from other investigations assessing the role of GnP after FOLFIRINOX in MPA (Table 4). In a previous meta-analysis of retrospective studies that evaluated the activity of GnP in the second-line, ORRs ranged from 0% to 25% and DCRs ranged from 25% to 64% (24). Additionally, mOS ranged from 4.6 to 12.4 months and mPFS ranged from 2.4 to 6.4 months.

Two single-arm phase II studies evaluated the activity of GnP after FOLFIRINOX for patients with MPA. Mita et al. treated 30 patients (80% with metastatic disease) with standard GnP and demonstrated an ORR of 13.3% and a DCR of 46.7% (25). Additionally, the mOS and mPFS were 7.6 and 3.8 months, respectively. In the study by Huh et al., 40 patients (87.5% with metastatic disease) were treated with standard GnP for an ORR of 15.0% and a DCR of 87.5% (26). The mOS and mPFS were 9.9 and 5.8 months, respectively. One argument against the use of GnP for Western patients is that its activity had not been properly assessed in second-line, particularly in this subgroup of patients, and that Asian patients might derive greater benefit from GnP. Indeed, data from the JCOG1611/GENERATE and at least one meta-analysis of retrospective studies suggest Asian patients might benefit more from GnP as compared to Western ones (27,28). However, the recently presented subgroup analysis from the NAPOLI-3 failed to identify differences in treatment effect between Western and Asian patients (29), supporting the lack of differences in treatment efficacy based on ethnic background. Only one prospective study that enrolled Western patients evaluated the efficacy and safety of GnP in second-line (14). In this trial, 78 patients with MPA who experienced disease progression on first-line FOLFIRINOX and had tumor staining of at least 20% with the NPC-1C antibody (directed against MUC5A) determined by central immunohistochemistry were randomized to receive GnP with or without NPC-1C. The study failed to show any benefit in favor of the NPC-1C arm. However, the outcomes of patients treated in the GnP-only arm were disappointing. The ORR was only 3.1% and the mPFS was only 2.7 months. Despite these results, it is important to highlight that this was a biomarker-driven study. Indeed, preliminary pre-clinical evidence suggests tumors with high MUC5A expression are less sensitive to gemcitabine, which could explain the poor results of GnP in this trial (30).

In our study, we compared the efficacy and safety of GnP with that of single-agent gemcitabine in the second-line setting and demonstrated the combination is associated with numerically improved ORR (17.2% vs. 0.0%), DCR (48.3% vs. 23.1%), and mOS (5.6 vs. 4.5 months). Also, we observed a statistically significant increase in mPFS (3.7 vs. 2.3 months). These findings are in line with other investigations that describe higher efficacy of GnP when compared with single-agent gemcitabine. In the aforementioned meta-analysis, the pooled ORR (14.4% vs. 8.4%; P=0.04) and DCR (53.5% vs. 30.2%; P<0.001) were higher in GnP when compared to single-agent gemcitabine (24). Additionally, in a large French real-world study, GnP was associated with improved DCR (56% vs. 23%; P<0.001), mPFS (3.5 vs. 2.3 months; P<0.001), and mOS (7.1 vs. 4.7; P<0.001) (13). Therefore, GnP has systematically been associated with improved efficacy outcomes in comparison with single-agent gemcitabine in second-line setting.

Despite the increased efficacy of GnP, it is also associated with an increased frequency of adverse events (13,24), especially hematological ones. In our study, we observed a numerically higher number of hematological adverse events in patients treated with GnP, especially anemia (21.4% vs. 0.0%) and thrombocytopenia (27.6% vs. 12.0%). Therefore, the choice between GnP and single-agent gemcitabine has to take into account differences in toxicity profile. That said, we believe for older patients and patients with ECOG performance status 2, single-agent gemcitabine still continues to be a reasonable choice in the second-line setting.

One way to decrease toxicities is to use an attenuated version of the GnP protocol. Most often, gemcitabine and nab-paclitaxel are administered on days 1 and 15 every 28 days (31-33), but they can also be given on days 1 and 8 every 21 days (34). In our study, patients in the modified GnP arm received a biweekly GnP regimen, with or without a reduction in the doses of gemcitabine and/or nab-paclitaxel. In a large retrospective analysis from the USA using the nationwide Flatiron de-identified database, the outcomes of 1,317 patients treated with standard or modified GnP were compared (35). In first-line, treatment with modified GnP was associated with inferior conditional time on treatment and overall survival, suggesting patients should be treated with the standard schedule in this setting. However, there were no differences in treatment efficacy for patients treated in second-line, suggesting this could be an option, especially for those more prone to adverse events, such as older patients, those with compromised performance status, and those with insufficient bone marrow reserve or significant previous peripheral neuropathy. Currently, there is limited data from randomized clinical trials to guide treatment modifications in the GnP regimen. In a small phase II Japanese trial, 60 elderly patients with MPA were treated in first-line with either standard GnP or dose-attenuated GnP (gemcitabine 250 mg/m² plus nab-paclitaxel 125 mg/m²) (36). The authors used this dose of gemcitabine-based on the saturation of intracellular gemcitabine triphosphate (a metabolite of gemcitabine) formation at doses of 350 mg/m² or higher. There were no differences in ORR (36.7% vs. 33.3%), DCR (76.7% vs. 83.3%), and mPFS (6.7 vs. 7.4 months) between patients treated with low-dose and normal-dose gemcitabine (plus nab-paclitaxel). Interestingly, rates of treatment-related adverse events were similar between the two dose groups. Despite a numerically shorter mOS, this study highlights the feasibility of using alternative doses without jeopardizing treatment efficacy. Given the limited number of patients included in our analysis, specially the ones treated with modified GnP, we refrained from comparing outcomes and toxicity between patients treated with standard and modified GnP. However, we did observe some long-term disease-free survival intervals for patients treated with modified GnP, highlighting the potential for the schedule modifications, especially for patients with worse performance status or more prone to toxicity. Additionally, the biweekly regimen is more convenient for patients, especially for those who live far from their treatment facilities.

Our investigation has limitations. First, its retrospective design is inherently susceptible to bias. Second, its modest sample size limited the statistical power of the tests used in our analyses. Third, ORR, DCR, and progression-free survival were not assessed by RECIST. Fourth, the limited sample size hampered the comparison between standard and modified GnP. Finally, we could not collect data on the dose intensity of GnP. However, our study also has merits. To the authors’ knowledge, it is the first South American investigation to assess the efficacy of GnP in the treatment of MPA after progression on FOLFIRINOX. Also, we provide detailed data regarding efficacy and safety outcomes. At last, we present useful information regarding the choice of second-line therapy and the possibility of using a modified GnP protocol that can decrease treatment-related adverse events.

Conclusions

After disease progression on FOLFIRINOX during first-line, GnP is associated with modestly improved treatment effectiveness when compared to single-agent gemcitabine, but also increased rates of adverse events. Treatment outcomes with GnP in second-line for Latin American patients with MPA seems to mirror those found in other investigations in the West and in the East. Outcomes of patients with MPA treated in the second-line setting continue to be poor and new treatment strategies are needed. While these promising drugs are not clinically available, GnP seems to be a reasonable option after progression on first-line FOLFIRINOX.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://apc.amegroups.com/article/view/10.21037/apc-25-5/rc

Data Sharing Statement: Available at https://apc.amegroups.com/article/view/10.21037/apc-25-5/dss

Peer Review File: Available at https://apc.amegroups.com/article/view/10.21037/apc-25-5/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-25-5/coif). T.C.F. has received a research grant from Servier Brazil, consulting fees from Knight Therapeutics, travel support from Servier Brazil, and honoraria from Servier Brazil. V.H.F.d.J. has received consulting fees, travel support, and honoraria from Servier Brazil. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was conducted at A.C. Camargo Cancer Center and was approved by the A.C. Camargo Cancer Center Internal Ethical Review Board (No. CAAE 71605423.4.0000.5432). Due to its retrospective nature, the need for an informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. GLOBOCAN. Cancer Today. 2020. Available online: https://gco.iarc.fr/today/2024
2. Saika K, Charvat H. Projection of the number of new cases of pancreatic cancer in the world. Jpn J Clin Oncol 2024;54:737-8. [Crossref] [PubMed]
3. Fonseca de Jesus VH, Guedes Camandaroba MP, Spina Donadio MD, et al. Clinico-pathological features and survival of patients with malignant exocrine pancreatic neoplasms: The AC Camargo Cancer Center experience. J Surg Oncol 2019;119:71-8. [Crossref] [PubMed]
4. Mastrantoni L, Chiaravalli M, Spring A, et al. Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis. Lancet Oncol 2024;25:1655-65. [Crossref] [PubMed]
5. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-25. [Crossref] [PubMed]
6. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369:1691-703. [Crossref] [PubMed]
7. Falzone L, Bordonaro R, Libra M. SnapShot: Cancer chemotherapy. Cell 2023;186:1816-1816.e1.
8. Portal A, Pernot S, Tougeron D, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer 2015;113:989-95. [Crossref] [PubMed]
9. Nguyen KT, Kalyan A, Beasley HS, et al. Gemcitabine/nab-paclitaxel as second-line therapy following FOLFIRINOX in metastatic/advanced pancreatic cancer-retrospective analysis of response. J Gastrointest Oncol 2017;8:556-65. [Crossref] [PubMed]
10. Ozaka M, Sasaki T, Yamada I, et al. Secondline treatment of modified FOLFIRINOX or nab-paclitaxel plus Gemcitabine for metastatic pancreatic adenocarcinoma. J Clin Oncol 2018;36. abstract 458.
11. Chae H, Jeong H, Cheon J, et al. Efficacy and safety of second-line nab-paclitaxel plus gemcitabine after progression on FOLFIRINOX for unresectable or metastatic pancreatic ductal adenocarcinoma: multicenter retrospective analysis. Ther Adv Med Oncol 2020;12:1758835920923424. [Crossref] [PubMed]
12. Sezgin Y, Karhan O, Aldemir MN, et al. Efficacy of gemcitabine plus nab-paclitaxel in second-line treatment of metastatic pancreatic cancer. Sci Rep 2025;15:11675. [Crossref] [PubMed]
13. Zaibet S, Hautefeuille V, Auclin E, et al. Gemcitabine + Nab-paclitaxel or Gemcitabine alone after FOLFIRINOX failure in patients with metastatic pancreatic adenocarcinoma: a real-world AGEO study. Br J Cancer 2022;126:1394-400. [Crossref] [PubMed]
14. Huffman BM, Basu Mallick A, Horick NK, et al. Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial. JAMA Netw Open 2023;6:e2249720. [Crossref] [PubMed]
15. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events. 2017. Available online: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf (accessed August 5th, 2024 2024).
16. de Jesus VHF, Camandaroba MPG, Donadio MDS, et al. Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX. J Gastrointest Oncol 2018;9:806-19. [Crossref] [PubMed]
17. De La Fouchardière C, Malka D, Cropet C, et al. Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study. J Clin Oncol 2024;42:1055-66. [Crossref] [PubMed]
18. Hassan MS, Awasthi N, Ponna S, et al. Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers-Improvements in Clinical Efficacy and Safety. Biomedicines 2023;11:2000. [Crossref] [PubMed]
19. Chiorean EG, Von Hoff DD. Taxanes: impact on pancreatic cancer. Anticancer Drugs 2014;25:584-92. [Crossref] [PubMed]
20. Untch M, Jackisch C, Schneeweiss A, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol 2016;17:345-56. [Crossref] [PubMed]
21. Gluz O, Kuemmel S, Nitz U, et al. Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial. Ann Oncol 2023;34:531-42. [Crossref] [PubMed]
22. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30:2055-62. [Crossref] [PubMed]
23. Yoneshima Y, Morita S, Ando M, et al. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol 2021;16:1523-32. [Crossref] [PubMed]
24. de Jesus VHF, Camandaroba MPG, Calsavara VF, et al. Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer. Ther Adv Med Oncol 2020;12:1758835920905408. [Crossref] [PubMed]
25. Mita N, Iwashita T, Uemura S, et al. Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure. J Clin Med 2019;8:761. [Crossref] [PubMed]
26. Huh G, Lee HS, Choi JH, et al. Gemcitabine plus Nab-paclitaxel as a second-line treatment following FOLFIRINOX failure in advanced pancreatic cancer: a multicenter, single-arm, open-label, phase 2 trial. Ther Adv Med Oncol 2021;13:17588359211056179. [Crossref] [PubMed]
27. Ohba A, Ozaka M, Ogawa G, et al. 1616O Nab-paclitaxel plus gemcitabine versus modified FOLFIRINOX or S-IROX in metastatic or recurrent pancreatic cancer (JCOG1611, GENERATE): A multicentred, randomized, open-label, three-arm, phase II/III trial. Ann Oncol 2023;34:S894.
28. Lee YS, Lee JC, Kim JH, et al. Pharmacoethnicity of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: a systematic review and meta-analysis. Sci Rep 2021;11:20152. [Crossref] [PubMed]
29. Lee W, Kim IH, Oh SC, et al. 324P Effect of NALIRIFOX in Asian patients (pts) with treatment-naive metastatic pancreatic adenocarcinoma (mPAC): Results from the NAPOLI 3 trial. Ann Oncol 2024;35:S136-S137.
30. Manne A, Kasi A, Esnakula AK, et al. Predictive Value of MUC5AC Signature in Pancreatic Ductal Adenocarcinoma: A Hypothesis Based on Preclinical Evidence. Int J Mol Sci 2023;24:8087. [Crossref] [PubMed]
31. Rehman H, Chi J, Hakim N, et al. Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer. Therap Adv Gastroenterol 2020;13:1756284820974912. [Crossref] [PubMed]
32. Rogers JE, Mizrahi JD, Xiao L, et al. Modified gemcitabine plus nab-paclitaxel regimen in advanced pancreatic ductal adenocarcinoma. Cancer Med 2020;9:5406-15. [Crossref] [PubMed]
33. Ahn DH, Krishna K, Blazer M, et al. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol 2017;9:75-82. [Crossref] [PubMed]
34. Chang C, Meng L, Li X, et al. A Modified Regimen of 21-day Nab-Paclitaxel Plus Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Real-World Study. Cancer Control 2022;29:10732748221141233. [Crossref] [PubMed]
35. Winer A, Handorf E, Dotan E. Dosing Schedules of Gemcitabine and nab-Paclitaxel for Older Adults With Metastatic Pancreatic Cancer. JNCI Cancer Spectr 2021;5:pkab074. [Crossref] [PubMed]
36. Kamata K, Imai H, Matsumoto H, et al. 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. JGH Open 2023;7:659-66. [Crossref] [PubMed]