Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma

Sahai, Vaibhav; Catalano, Paul J.; Zalupski, Mark M.; Lubner, Sam Joseph; Menge, M; Nimeiri, Halla; Munshi, Hidayatullah G.; Benson, Al B.; O’Dwyer, Peter J.

doi:10.1001/jamaoncol.2018.3277

Cited by 111 publications

(99 citation statements)

References 22 publications

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“…The most frequent especially severe adverse events in this study were from hematologic toxicities, which were mainly attributed to chemotherapy. However, we observed that the incidence of grade 3 or higher thrombocytopenia was much higher than currently reported gemcitabine and cisplatin chemotherapy [4,5,7], whether the addition of nivolumab to chemotherapy deteriorated thrombocytopenia remained unclear. Indeed, thrombocytopenia was a common toxicity of immune checkpoint inhibitors [18][19][20].…”

Section: Discussionmentioning

confidence: 81%

“…However, this combination regimen confers a limited efficacy, one possible reason is the rich desmoplastic stroma of BTCs, forming a barrier to the delivery of chemotherapeutic drugs in the tumor bed, and resulting in resistance to chemotherapy. Other regimens or strategies, such as gemcitabine and oxaliplatin with or without cetuximab [5], capecitabine plus cisplatin [6], nab-paclitaxel and gemcitabine [7], and small molecule kinase inhibitors targeting FGFR, IDH, MET, Mesothelin, BRCA and other mutated genes, did not show significant improvements of efficacy and survival [8,9].…”

mentioning

confidence: 99%

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Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

Feng

Liu

Zhao

et al. 2020

Preprint

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Background: The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptable low. This study aimed to determine the efficacy, safety and predicting biomarkers of immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs.Methods: In this open-label, single-arm, phase Ⅱ trial, chemo-immunology combination therapy consisting of gemcitabine 1000mg/m2, cisplatin 75mg/m2 plus nivolumab 3mg/kg was administered every 3 weeks for up to 6 cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was objective response rate (ORR). Secondary outcomes included safety, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The exploratory objectives were to assess biomarkers for predicting clinical response and prognosis.Results: 32 patients with a median age of 60 (range 27-69) years were enrolled. As of September 31, 2019, the median follow-up was 12.8 (95% CI, 10.8-14.8) months. 27 response-evaluable patients received a median of 4 (IQR, 3-6) cycles combination therapy, of which 15 (55.6%) patients achieved objective response, including 5 (18.6%)with complete response (CR), and the DCR was 92.6%. 2 of 6 patients in cohort A who were refractory to gemcitabine or cisplatin-based chemotherapy achieved 1 CR and 1 partial response. 13 of 21 chemotherapy-naive patients (61.9%) in cohort B achieved objective response. The median PFS of all patients in cohort A+B was 6.1 months. The median OS was 8.5 months with 33.3% 12-month OS rate. The most frequent grade 3 or higher adverse events were thrombocytopenia (56%), and neutropenia (22%). Fitness might be a biomarker for predicting clinical response. On-therapy change of serum sFASL, MCP-1 and IFN-γ were correlated with prognosis.Conclusions: Nivolumab in combination with gemcitabine and cisplatin offer promising efficacy and manageable safety profile for patients with advanced BTCs.

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Section: Discussionmentioning

confidence: 81%

mentioning

confidence: 99%

Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

Feng

Liu

Zhao

et al. 2020

Preprint

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“…A final gemcitabine-based doublet that was explored in patients with advanced CCA is gemcitabine plus nab-paclitaxel. In 2018, Sahai et al [35] reported the results of a multicenter phase II trial in which 74 patients with advanced CCA were treated with nab-paclitaxel (125 mg/m 2 IV) followed by gemcitabine (1000 mg/m 2 on Days 1, 8, and 15) in 28-day treatment cycles [35] . The regimen was effective, with an ORR of 30% and a median OS of 12.4 months.…”

Section: Gemcitabine-based Doublet Chemotherapymentioning

confidence: 99%

Systemic therapy for advanced cholangiocarcinoma: new options on the horizon

Alqahtani¹,

Colombo²

2020

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Patients with unresectable cholangiocarcinoma (CCA) face a poor prognosis, and there are few effective treatment options for the disease. The standard of care for patients with locally advanced or metastatic CCA is chemotherapy with a gemcitabine-based doublet. Unfortunately, the clinical benefit obtained with these regimens is modest, with a median overall survival of about one year. For CCA that is chemotherapy-refractory or recurs after first-line chemotherapy, the treatment options are even more limited, and no relevant randomized controlled data are available. In recent years, molecular profiling has shed light on the molecular basis of CCA and identified subgroups of patients that might benefit from a personalized treatment approach. These efforts resulted in the recent FDA approval of the fibroblast growth factor receptor (FGFR) inhibitor, pemigatinib, as a second-line treatment for patients with advanced CCA harboring an FGFR2-fusion or rearrangement. Several other targeted agents also are under evaluation in patients with CCA, of which the isocitrate dehydrogenase inhibitor has had the most promising results. Finally, immunotherapy is being explored as a new treatment approach for advanced CCA patients; indeed, the immune checkpoint inhibitor pembrolizumab can already be used to treat CCAs that are mismatch repair deficient. This review is a comprehensive overview of the treatment options for CCA and offers a glimpse into what the future could hold for these patients.

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“…[10,11] To date, nab-paclitaxel has been approved by the United States Food and Drug Administration for the treatment of metastatic breast cancer, locally advanced or metastatic non-small cell lung cancer, and metastatic pancreatic cancer. [10,12] Not only that, there is growing evidence that nab-paclitaxel is effective in the treatment of other malignant tumors, [13,14] including STS. [15][16][17] Since January 2019, advanced sarcoma patients have been treated in our hospital (a major sarcoma treatment center in central China) with nab-paclitaxel and gemcitabine.…”

Section: Introductionmentioning

confidence: 99%

Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma

Tian

Zhang

et al. 2020

Preprint

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Background: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the clinical data and evidence of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare.Methods: The data of 17 patients with metastatic STS who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively reviewed. All patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the median progression-free survival (m-PFS), disease control rate (DCR), objective response rate (ORR) and adverse events (AEs) in these patients. Results: The m-PFS was 6 months (95% CI, 2–9 months), ORR was 41.2% and DCR was 70.6%. The average change in target lesion diameter from baseline was -19.06±45.74%. While the majority of the treatment patients experienced grade 1 or 2 AEs, grade 3 or 4 AEs were not common, but included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. Conclusion: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

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Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma

Abstract: ClinicalTrials.gov identifier: NCT02181634.

Cited by 111 publications

References 22 publications

Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study

Systemic therapy for advanced cholangiocarcinoma: new options on the horizon

Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma

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