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A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab.

ABSTRACT: T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)-targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data and recent literature. We acknowledge the limitations of such comparisons, but suggest that based on the available data, differences in clinical trial outcomes between nivolumab and pembrolizumab are more likely drug-independent than drug-dependent.

SUBMITTER: Fessas P

PROVIDER: S-EPMC5612055 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab.

Fessas Petros P Lee Hassal H Ikemizu Shinji S Janowitz Tobias T

Seminars in oncology 20170401 2

T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)-targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data a ...[more]

PMID: 28923212

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Preclinical comparison of prolgolimab, pembrolizumab and nivolumab.

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2024-08-01 | GSE268752 | GEO

Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy-free, first-line treatment for PD-L1-positive non-small cell lung cancer.

Project description:BackgroundNivolumab plus ipilimumab (N-I) or pembrolizumab (PEM) is associated with survival improvement as chemotherapy-free, first-line treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and positive programmed cell death ligand 1 (PD-L1). However, no direct comparison data exist between these two regimens to inform clinical decisions. Therefore, we performed indirect comparison for N-I versus PEM using frequentist methods.ResultsThree randomized trials (KEYNOTE-024, KEYNOTE-042, and CheckMate 227) involving 2372 patients were included. For patients with tumor PD-L1 level of ≥1%, pooled meta-analyses showed that both N-I and PEM improved overall survival (OS) relative to chemotherapy (N-I: hazard ratio [HR] 0.82, 95% CI 0.69-0.97; PEM: HR 0.81, 95% CI 0.71-0.93); whereas only N-I significantly improved progression-free survival (PFS) (N-I: HR 0.79, 95% CI 0.65-0.96; PEM: HR 1.07, 95% CI 0.94-1.21). Neither N-I nor PEM was associated with improved objective response rate (ORR) compared with chemotherapy (N-I: relative risk [RR] 1.20, 95% CI 0.98-1.46; PEM: RR 1.03, 95% CI 0.86-1.23). Indirect comparisons showed that N-I was associated with longer PFS than PEM (HR 0.77, 95% CI 0.62-0.95). However, N-I was not superior to PEM in terms of OS (HR 0.98, 95% CI 0.77-1.24) and ORR (RR 1.17, 95% CI 0.89-1.52). N-I showed a less favorable toxicity profile relative to PEM (all grade adverse events: RR 1.28, 95% CI 1.17-1.40).ConclusionsN-I and PEM provide comparable OS benefit for PD-L1-positive NSCLC. N-I further improves PFS relative to PEM but at meaningful cost of toxicities.

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A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC.

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| S-EPMC7762014 | biostudies-literature

Indirect comparison between immune checkpoint inhibitors and targeted therapies for the treatment of melanoma.

Project description:Background: This systematic review and meta-analysis aims to provide comparative and quantitative data about immune checkpoint inhibitor (IMM) and targeted therapy (TAR) in this work. Methods: A literature search was performed with PubMed, Embase, PMC database, and Web of Science databases to identify relevant studies. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for overall response rate (ORR) were estimated. Results: Eighteen manuscripts were ultimately utilized for indirect comparisons. In general, both TAR and IMM can prolong the PFS either by monotherapy, combination therapy with chemotherapy or adjuvant therapy. BRAF inhibitor monotherapy showed superiority over anti-CTLA-4 in OS (HR: 1.28, 95%CI: 0.93-1.75) and best ORR (OR: 12.57, 95%CI: 6.63-23.82), as well as longer PFS (HR: 1.63, 95%CI: 1.00-2.67) and higher best ORR (OR: 3.29, 95%CI: 1.94-5.55) compared with anti-PD-1. However, MEK inhibitor monotherapy showed no priority. When combined with chemotherapy, anti-CTLA-4 showed marginally advantages over MEK inhibitor in OS (HR: 0.68, 95%CI: 0.44-1.03), however no advantage in PFS (HR: 1.12, 95%CI: 0.76-1.64), or ORR (OR: 1.78, 95%CI: 0.70-4.49). For post-operational melanoma patient, adjuvant TAR and adjuvant IMM showed no difference in OS (HR: 1.14, 95%CI: 0.82-1.58) or PFS (HR: 1.20, 95%CI: 0.79-1.83). Moreover, the high-rate adverse events and underlying diseases should be considered during the application of those agents. Conclusions: For the unresectable late-stage melanoma, IMM may be a better choice for the combined treatment with chemotherapy. If the chemotherapy is not tolerable for patients, BRAFi involved TAR can be considered.

| S-EPMC6856565 | biostudies-literature

Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors.

Project description:PurposeImmune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti-PD-1 pathway-targeted therapy.Patients and methodsPatients with metastatic RCC who received prior anti-PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed.ResultsForty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients.ConclusionIpilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

| S-EPMC7499610 | biostudies-literature

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