Efficacy and safety of pembrolizumab in advanced neuroendocrine tumors (NETs): A meta-analysis of clinical trials.

Authors

Akshit Chitkara

Akshit Chitkara

University of California, Riverside, Riverside, CA

Akshit Chitkara , Rushin Patel , Fnu Anamika , Chieh Yang , Zalak Patel , Femina Patel , Mrunal Patel , Jasninder Dhaliwal , Bhuvaneswari Ramaswamy

Organizations

University of California, Riverside, Riverside, CA, Community Hospital of San Bernardino, San Bernardino, CA, Hackensack Meridian Ocean University Medical Center, Brick, NJ, University of California Riverside, San Bernardino, CA, University of California Riverside, Riverside, CA, Trumbull Regional Medical Center, Western Reserve, Warren, OH, The Ohio State University Wexner Medical Center, Columbus, OH

Research Funding

No funding received
None.

Background: Patients with recurrent or metastatic neuroendocrine tumors (NETs) have limited treatment options and a poor prognoses. Programmed death–ligand 1 (PD-L1) has been associated with the pathogenesis, progression, and prognosis of NETs. This article analyzes the efficacy and safety profile of PDL1 inhibitor Pembrolizumab in advanced NETs. Our objective is to identify all the clinical trials in which Pembrolizumab has been assessed in treating NETs and to evaluate the efficacy and safety profile in this patient population with high power. Methods: Systemic searches of PubMed, the Cochrane Library, and ClinicalTrials.gov were conducted with prespecified terms. The outcomes studied in our analysis were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and serious adverse events (AEs). We calculated the pooled ORR for these studies using weighted pooled ORR = Σ (ORR_i * weight_i). We calculated the standard error using the formula SE = √(Σ (wi x (1 - ORRi) x ORRi) / Σ (wi x ni)) and the 95% confidence interval using the formula CI = ORR ± (1.96 x SE). This statistical method was also used to calculate our study's pooled DCR, PFS, OS, and serious AEs. However, it is essential to note that the pooled data is only as reliable as the individual data estimates from each study and may be subject to bias or confounding factors. Results: Five clinical trials met the inclusion criteria, including patients with gastrointestinal, pancreatic, lung, and lower genital tract NETs. Outcome data were available for all five studies, comprising 177 patients with NETs who received Pembrolizumab as part of the treatment regimen (Table). The pooled ORR and DCR were 5.27% (95% CI 2.23-8.31) and 5.4% (95% CI 3-7.8), respectively. The pooled weighted PFS was 4.4 months, and pooled weighted OS was 23.3 months. These findings suggest that Pembrolizumab has a promising ORR, DCR, PFS, and OS. Safety was a secondary endpoint, and the pooled serious AEs were noted in 20.9% of patients. Conclusions: Pembrolizumab demonstrated statistically significant efficacy and safety profile in a subset of patients with NETs and was overall well-tolerated. In recent years, the combination strategy of tyrosine kinase inhibitors (TKI) with PDL-1 checkpoint inhibitors has shown promising clinical benefits in patients with various solid tumors. Further studies are needed to analyze the efficacy and safety of TKI with PD-L1 inhibitors in NETs.

National clinical trialNETs typeORR%DCR%PFS (Months)OS (Months)Serious AE%
NCT02054806Carcinoid12.012%5.621.120
NCT02054806Pancreatic6.36.254.521.06.3
NCT02628067Lung, Gastroentero-pancreatic (GEP)3.73.744.124.221.5
NCT02721732Lower Genital TractNot available (NA)NA2.1NA29
NCT03043664GEP4.5NA5.4NA27.27
Pooled analysisAll NETs5.27 (95% CI 2.23-8.31)5.4 (95% CI 3 - 7.8)4.423.320.90

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Abstract Details

Meeting

2023 ASCO Breakthrough

Session Type

Poster Session

Session Title

Poster Session A

Track

Breast Cancer,Central Nervous System Tumors,Developmental Therapeutics,Genitourinary Cancer,Hematologic Malignancies,Thoracic Cancers,Other Malignancies or Topics

Sub Track

Targeted Therapies

Citation

JCO Global Oncology 9, 2023 (suppl 1; abstr 165)

DOI

10.1200/GO.2023.9.Supplement_1.165

Abstract #

165

Poster Bd #

G9

Abstract Disclosures