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Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer.

ABSTRACT: Due to HAART and consequent decline in mortality from infectious complications, HIV patients have an increasing burden of non-AIDS defining cancers. Data on their safety and efficacy is unknown as these patients were excluded from clinical trials due to concern of unforeseen side effects. Objectives. The main objective of our study was to evaluate the efficacy and safety profile of PD-1 and PD-L1 inhibitors in HIV patients being treated for advanced cancers and to assess the impact of these drugs on HIV status of the patients specifically CD4 count and HIV viral load. Materials and Methods. This was a retrospective analysis of data of 17 patients HIV treated with one of the PD-1/PD-L1 inhibitors (Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, or Avelumab) for advanced cancer. Results. 10 out of 17 patients responded to therapy. 7 patients, all of whom had shown response to therapy, were alive and 4 were still on checkpoint inhibitor. 10 patients including all 7 nonresponders had died. Responders had minimum of 15 weeks of response while one had ongoing continued response at 34 weeks. Side effects were seen in 7 patients and only one patient needed cessation of therapy. CD4 counts were stable on treatment while HIV RNA remained undetectable. Conclusion. PD-1 and PD-L1 inhibitors appear to have comparable efficacy and tolerable side effect profile and have no effect on HIV markers when used in HIV patients with advanced cancers.

SUBMITTER: Bari S

PROVIDER: S-EPMC6582789 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer.

Bari Shahla S Muzaffar Jameel J Chan Austin A Jain Sanjay R SR Haider Ahmad M AM Adams Curry Marjorie M Hostler Christopher J CJ

Journal of oncology 20190101

Due to HAART and consequent decline in mortality from infectious complications, HIV patients have an increasing burden of non-AIDS defining cancers. Data on their safety and efficacy is unknown as these patients were excluded from clinical trials due to concern of unforeseen side effects. <i>Objectives</i>. The main objective of our study was to evaluate the efficacy and safety profile of PD-1 and PD-L1 inhibitors in HIV patients being treated for advanced cancers and to assess the impact of the ...[more]

PMID: 31275380

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Project description:Objectives: Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression. Patients and Methods: A tissue microarray was constructed using 368 samples of TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations with clinicopathologic characteristics were analyzed. PD-L1high was designated as ?50% of tumor proportion score; PD-1high and CD8high were defined as ?5% and 1% of tumoral immune cells, respectively. Results: The cohort consisted of 308 patients with thymomas and 60 patients with TC. PD-L1 positivity was identified in 90.6% (328/362, ?1%) of TETs, PD-1 expression of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ?1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1high). The PD-L1high thymoma group was correlated with high Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myasthenia gravis (p < 0.001). This group exhibited poor overall survival (OS, p = 0.003, log-rank) and worse disease-free survival (DFS, p = 0.042, log-rank). No survival differences were detected between PD-L1high and PD-L1low groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1high expression was an independent poor prognostic factor (p = 0.047, HR 2.087, 95% CI, 1.009-4.318) in thymomas. Conclusions: To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.

Project description:BackgroundInhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have represented a novel approach for the management of advanced non-small cell lung cancer (NSCLC). In this study, we aimed to estimate five anti-PD-1/L1 agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab) using network meta-analyses (NMAs) and the Bayesian method to provide suggestions for advanced NSCLC treatments.MethodsWe searched PubMed, Web of Science, Embase, and the Wiley Online Library for eligible studies published up to March 2020. Both pairwise analyses and NMAs were conducted with clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate, and the incidences of adverse events. Results were presented in several patient populations according to treatment lines and PD-L1 status.ResultsNineteen randomized clinical trials (RCTs) involving 11,456 patients were included in our study. PD-1/L1 inhibitors showed significant benefits over chemotherapies in OS regardless of tumor PD-L1 status [first-line settings: OS =0.85, 95% CI (0.77, 0.94), I2=37%; second- or further-line settings: OS =0.77, 95% CI (0.71, 0.84), I2=37%]. The combined regimen of pembrolizumab and chemotherapy stood out to be the most effective and safest for patients in the first-line settings. Pembrolizumab monotherapy was showed to be the best especially for patients with PD-L1 ≥50%. In the subsequent-line settings, nivolumab ranked the best in improving the survival of patients, and durvalumab had the greatest effect in tumor shrinkage. Atezolizumab, followed by nivolumab, ranked the safest in reducing adverse events, whereas durvalumab was showed with the largest side effects among the five inhibitors.ConclusionsThe combination of pembrolizumab with chemotherapy is suitable for advanced NSCLC patients who have not received any systematic treatments before, and pembrolizumab monotherapy should also be considered, especially for patients with highly-expressed PD-L1 (≥50%). Nivolumab is the best option for patients with advanced NSCLC whose tumors have progressed following chemotherapies or combined modalities of treatments including chemotherapy. However, our results need to be further validated in future head-to-head clinical trials.

Dataset Information

Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer.

Publications

Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer.

Similar Datasets

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