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First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy.

ABSTRACT: Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18-2.23) and PFS (HR 0.55, 0.32-0.97). A trend towards improved OS was also observed (HR 0.76, 0.51-1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6500047 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy.

Zhou Yixin Y Lin Zuan Z Zhang Xuanye X Chen Chen C Zhao Hongyun H Hong Shaodong S Zhang Li L

Journal for immunotherapy of cancer 20190503 1

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), ...[more]

PMID: 31053172

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Project description:Background and objectiveSintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China.MethodsFrom the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results.ResultsCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1-3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1-3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy.ConclusionCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.

Project description:BackgroundPembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy.Patients and methodsIn the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 (≥1% staining, assessed using a prototype assay) were randomly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 (Q3W) or 2 (Q2W) weeks. Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received ≥1 pembrolizumab dose. Using pre-treatment tumor tissue, a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score (TPS).ResultsBetween 1 March 2013 and 18 September 2015, 101 patients received pembrolizumab 2 mg/kg Q3W (n = 6), 10 mg/kg Q3W (n = 49), or 10 mg/kg Q2W (n = 46). Of these, 27 (26.7%) had TPS ≥50%, 52 (51.5%) had TPS 1%-49%, and 12 (11.9%) had TPS <1%. The objective response rate (ORR) was 27% (27/101, 95% CI 18-37) and median overall survival was 22.1 months (95% CI 17.1-27.2). In patients with PD-L1 TPS ≥50%, ORR, 12-month PFS, and 12-month OS were higher [14/27 (51.9%; 95% CI 32%-71%), 54%, and 85%, respectively] than the overall population [27/101 (26.7%; 95% CI 18.4%-36.5%), 35%, 71%]. Pembrolizumab was well tolerated, with only 12 (11.9%) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths.ConclusionsPembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS ≥50%.Clinical trial name and numberKEYNOTE-001 (ClinicalTrials.gov, NCT01295827).

Dataset Information

First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy.

Publications

First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy.

Similar Datasets

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