Dataset Information

Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma.

ABSTRACT: Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown. Methods:This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1. Results:Thirty-two patients received second-line and above treatment with LEP. Overall, the objective response rate (ORR) was 25%, the disease control rate (DCR) was 78.1%, and the clinical benefit rate (CBR) was 40.5%. The median progression-free survival (PFS) was 4.9 months (95% CI: 4.7-5.2 months), and the median overall survival (OS) was 11.0 months (95% CI: 9.6-12.3 months). For tolerability, no grade 5 serious adverse events (AEs) were reported. All patients had any-grade AEs, and 59.3% of the patients experienced grade 3 AEs, while only 1 patient experienced a grade 4 AE of stomach bleeding. Fatigue was the most common AE, followed by hypertension and elevated aminotransferase levels. Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes. Conclusions:LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC. Furthermore, well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.

SUBMITTER: Lin J

PROVIDER: S-EPMC7423565 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma.

Lin Jianzhen J Yang Xu X Long Junyu J Zhao Songhui S Mao Jinzhu J Wang Dongxu D Bai Yi Y Bian Jin J Zhang Lei L Yang Xiaobo X Wang Anqiang A Xie Fucun F Shi Weiwei W Yang Huayu H Pan Jie J Hu Ke K Guan Mei M Zhao Lin L Huo Li L Mao Yilei Y Sang Xinting X Wang Kai K Zhao Haitao H

Hepatobiliary surgery and nutrition 20200801 4

<h4>Background</h4>A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown.<h4>Methods</h4>This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment ...[more]

PMID: 32832493

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Project description:Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US). Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model's robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY). Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.

Project description:BackgroundPatients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.MethodsIn this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.ResultsThe median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%).ConclusionsPembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).

Project description:Biliary tract carcinoma (BTC) has a poor prognosis and is increasing in incidence. Although surgery, chemotherapy and other treatment modalities have improved, surgery remains the only potential curative treatment and is appropriate for only those few patients who present with localized, resectable disease. However, for the majority of patients, unresectable disease is evident at diagnosis and about 95% of patients die within 10 years, despite the majority receiving chemotherapy. Long-term survival is significantly greater for patients with resected BTC compared to those with unresectable disease. In unresected disease, life expectancy is limited, with first-line gemcitabine/cisplatin (GEM/CIS) accepted as standard of care. Currently no standard second-line regimen which provides significant improvement of clinical outcomes exists for those who present with refractory disease or who relapse after first-line treatment. Of particular importance is establishing the impact of best supportive care (BSC) as a benchmark for survival outcomes to which the impact of treatment modalities can be compared. Survival outcome often differs significantly for patients with different prognostic factor profiles even when receiving the same therapy so that it can be difficult to predict which patient subgroup might benefit most from which therapy. Therefore, the influence of prognostic factors on survival under different therapies as well as under BSC needs to be further assessed in order to arrive at truly evidence-based, best therapeutic decisions for individual patients. Encouraging new research into the genomic landscape of BTC may help to further subdivide the BTC population into molecular-genetic clusters likely to be sensitive to different targeted therapy approaches leading to further improvements in survival. Consequently, an unmet need exists not only to develop new and more effective therapies for this devastating disease, but also to integrate original research findings into a more complex, dynamic, individualized therapeutic decision model to aid clinicians in making evidence-based, best therapeutic decisions for individual patients.

Dataset Information

Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma.

Publications

Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma.

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