Keynote 42: Pembrolizumab, PD-L1, and where to draw the line.
Ontology highlight
ABSTRACT:
SUBMITTER: Isaacs J
PROVIDER: S-EPMC7210198 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Keynote 42: Pembrolizumab, PD-L1, and where to draw the line.
Isaacs James J Clarke Jeffrey J Ready Neal N
Annals of translational medicine 20200401 7
Similar Datasets
Project description:BackgroundIn the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population.Materials and methodsHRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated.ResultsThe HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [-0.16; 95% confidence interval (CI) -5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003).ConclusionsHRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1-positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population.
| S-EPMC8358416 | biostudies-literature
Project description: Not available
| S-EPMC7791256 | biostudies-literature
Project description: Not available
| S-EPMC6685853 | biostudies-literature
Project description: Not available
| S-EPMC5750169 | biostudies-literature
Project description: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%.
| S-EPMC6500047 | biostudies-literature
Project description: Not available
| S-EPMC7876893 | biostudies-literature
Project description:BackgroundPembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost-effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD-L1) test on the cost-effectiveness is also unknown. The current study assessed the cost-effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers' perspective.Materials and methodsA literature-based Markov model was conducted using KEYNOTE-189 trial data to compare cost and quality-adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro-chemotherapy combination and chemotherapy strategy without PD-L1 test, and treatment strategy according to their PD-L1 status.ResultsIn base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD-L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD-L1 test strategy. In the PD-L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD-L1 test strategy. Lowering Pembro price can also partly decrease the ICERs.ConclusionCompared with chemotherapy, the combination strategy is not cost-effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD-L1 test for patient selection and price reduction could improve the cost-effective probabilities of immunotherapy for nonsquamous NSCLC.
| S-EPMC7050096 | biostudies-literature
Project description:The identification of prognostic and predictive biomarkers for high-programmed cell death-ligand 1 (PD-L1) advanced non-small cell lung cancer (aNSCLC) treated with first-line pembrolizumab could support the decision-making about possible combination therapies. To explore the baseline neutrophil-to-lymphocyte ratio (NLR) with the possible addition of PD-L1 tumour proportion score (TPS) level or lactate dehydrogenase (LDH) as possible prognostic biomarkers by a multicenter retrospective exploratory analysis aiming at identifying favourable-risk patients. Baseline NLR was available for all 132 high PD-L1 aNSCLC patients, PD-L1 level and LDH for 81 (61%) and 85 (64%) patients, respectively. NLR, PD-L1 and LDH cut-offs by receiver operating characteristic (ROC) curves were 4.9, 77.5% and 268.5, respectively. Seventy-one patients (54%) had NLR <5; 25 out of 81 NLR <5 (31%) had PD-L1 >80%, 26 out of 85 (31%) NLR <5 and normal LDH (nLDH). Median follow-up was 16.3 months. As compared to NLR >5, significantly better 2-year overall survival (OS) and progression-free survival (PFS) were observed with NLR <5 [62% vs. 41%, P=0.005, hazard ratio (HR) 0.45, and median of 12.0 vs. 5.7 months, P=0.01, HR 0.56, respectively], NLR <5 + PD-L1 >80% (81%, P=0.006, HR 0.20 and median of 14.7, P=0.03, HR 0.44, respectively), and NLR <5 + nLDH (74%, P=0.009, HR 0.25 and median of 14.7, P=0.02, HR 0.40, respectively). NLR <5 and NLR <5 + nLDH significantly associated with PD (P=0.008 and P=0.025, respectively) but not response rate (RR) (P=0.09 and P=0.07, respectively); NLR <5 + PD-L1 >80% both RR (P=0.03) and PD (P=0.02). NLR <5 ± PD-L1 >80% or nLDH could represent easy-to-assess tools to identify high PD-L1 aNSCLC patients with favourable outcome following first-line pembrolizumab monotherapy.
| S-EPMC7481583 | biostudies-literature
Project description: Lung cancer is currently the malignant tumor with the highest incidence and mortality in the world, while non-small cell lung cancer (NSCLC) is the most common pathological type of lung caner. In the past few decades, the only treatment options available for advanced NSCLC patients have been targeted therapy or chemotherapy, but these therapies are inevitably tolerated by tumors. The discovery of immune checkpints that mediate the immune escape of tumor cells have been promoting a series of immune checkpoint inhibitors to be used in cancer treatment and achieved great results. Among them, pembrolizumab is currently the only PD-1 inhibitor approved for first-line treatment of NSCLC, whether it is monotherapy or combination therapy, for creditable performance in KEYNOTE studies. In this review, we systematically integrate the latest series of clinical trial results, pharmacological mechanisms, adverse events (AEs) and predictive biomarkers in the first-line treatment of NSCLC. We hope pembrolizumab could become a better choice for more clinicians and benefit more patients with advanced NSCLC.
| S-EPMC7395702 | biostudies-literature
Project description:BackgroundThe phase 3 KEYNOTE-590 (NCT03189719) study showed first-line pembrolizumab plus chemotherapy significantly prolonged overall survival and progression-free survival versus placebo plus chemotherapy in patients with advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction. We describe a subgroup analysis of Japanese patients from KEYNOTE-590.MethodsEligible patients were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Efficacy was evaluated in all Japanese patients and those with esophageal squamous cell carcinoma and programmed death ligand 1 combined positive score ≥ 10. Dual primary endpoints were overall survival and progression-free survival per RECIST v1.1 by investigator. Secondary endpoints included objective response rate per RECIST v1.1 by investigator and safety and tolerability.ResultsAt data cutoff (July 2, 2020), 141 Japanese patients were randomly assigned (pembrolizumab plus chemotherapy, 74; placebo plus chemotherapy, 67). In all Japanese patients, median overall survival was 17.6 months with pembrolizumab plus chemotherapy versus 11.7 months with chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.47-1.09), median progression-free survival was 6.3 versus 6.0 months (hazard ratio, 0.58; 95% confidence interval, 0.40-0.84), and objective response rate was 56.8% versus 38.8%. Grade 3-5 treatment-related adverse events were 74.3% and 61.2%.ConclusionFirst-line pembrolizumab plus chemotherapy demonstrated improvement in overall survival and progression-free survival compared with placebo plus chemotherapy in Japanese patients with advanced/metastatic esophageal cancer; safety was comparable between treatment groups.Clinical trial registryClinicalTrials.gov, NCT03189719.
| S-EPMC9436840 | biostudies-literature