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Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) has the worst prognosis among all molecular types of breast cancer. Because of the strong immunogenicity of TNBC cells, programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, two kinds of immune checkpoint blockade agents, might help improve the prognosis of TNBC. However, how to better use PD-1/PD-L1 inhibitors and select patients who may benefit from treatment options remains controversial. This article summarizes published clinical studies in which PD-1/PD-L1 inhibitors were used in patients with advanced TNBC to explore how to maximize effectiveness of these medications.

SUBMITTER: Liang Y

PROVIDER: S-EPMC9086576 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer.

Liang Yuehua Y Liu Xiaoran X Li Kun K Li Huiping H

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20220401 2

Triple-negative breast cancer (TNBC) has the worst prognosis among all molecular types of breast cancer. Because of the strong immunogenicity of TNBC cells, programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, two kinds of immune checkpoint blockade agents, might help improve the prognosis of TNBC. However, how to better use PD-1/PD-L1 inhibitors and select patients who may benefit from treatment options remains controversial. This article summarizes published clinical studies i ...[more]

PMID: 35685994

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Project description:IntroductionProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings.MethodsExtensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis.ResultsTen nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1-21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3-14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9-27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5-2.9 vs. 2.0-2.7 months and 7.9-18.2 vs. 15.9 months) and second-line chemotherapy (3.3-4.0 months and 7.4-8 months). Odds of achieving ORR was 0.10 (95% CI 0.03-0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19-0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible.ConclusionsPD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care.

Project description:Background and objectiveLung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment. Programmed death-ligand 1 (PD-L1) expression is one of the most valuable biomarkers for predicting the efficacy of lung cancer immunotherapy. Several studies have confirmed that patients with high PD-L1 expression are more likely to benefit from immunotherapy, but there is a high proportion of people with negative PD-L1 expression constituting a patient population that cannot be ignored. This article reviews the distribution of PD-L1 expression, the methods for evaluating PD-L1, and the effectiveness of immunotherapy for advanced NSCLC with negative PD-L1 expression.MethodsWe performed a literature review to identify relevant data published until September 2022. In order to organize related information, we searched for literature in PubMed; abstracts and reports published in the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference on Lung Cancer (WCLC), and other congresses; and clinical trial information registered on ClinicalTrials.gov. Information on the distribution of PD-L1 expression, detection of PD-L1, and immunotherapy efficacy for NSCLC with negative PD-L1 expression was collated and reviewed.Key content and findingsThe incidence of PD-L1 expression in patients with stage IIIB/IV NSCLC is similar in all regions of the world, but PD-L1 expression level is associated with certain clinicopathological features. The expression of PD-L1 can be evaluated by various detecting methods. Some immunotherapy regimens have better efficacy than traditional chemotherapy in patients with negative PD-L1 expression.ConclusionsPatients with NSCLC and negative PD-L1 expression can receive better survival benefits under some immunotherapy types, and these may represent a better treatment option for this relatively small patient population.

Project description:IntroductionThe clinical successes seen with anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors.MethodsWe identified clinical trials involving anti-PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials.ResultsWe found 686 clinical trials investigating anti-PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration's approval of an anti-PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy.ConclusionsThe number of clinical trials investigating anti-PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.

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Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer.

Publications

Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer.

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