Trial reportCancer2018
NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin 2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma.
Trial report in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Order of patient entry and outcomes in phase II clinical trials: A meta-analysis of individual patient data.Contemporary clinical trials · 2023Pooled it
- Current Therapies and Potential Strategies for Uveal Melanoma.Drugs and drug candidates · 2025Article
- Uveal melanoma with a GNA11/GNAQ mutation secretes VEGF for systemic spread.Signal transduction and targeted therapy · 2025Article
- Melanoma-derived extracellular vesicles transfer proangiogenic factors.Oncology research · 2025Review
- Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.Cancers · 2023Review
- Polypharmacological Cell-Penetrating Peptides from Venomous Marine Animals Based on Immunomodulating, Antimicrobial, and Anticancer Properties.Marine drugs · 2022Article
- State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain.Neurosurgical review · 2022Review
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
- NK and cells with NK-like activities in cancer immunotherapy-clinical perspectives.Medical oncology (Northwood, London, England) · 2022Review
- Enhanced immune activation within the tumor microenvironment and circulation of female high-risk melanoma patients and improved survival with adjuvant CTLA4 blockade compared to males.Journal of translational medicine · 2022Article
- The role of angiogenesis in melanoma: Clinical treatments and future expectations.Frontiers in pharmacology · 2022Review
- Hypoxia-dependent drivers of melanoma progression.Journal of experimental & clinical cancer research : CR · 2021Review
- (Im)maturity in Tumor Ecosystem.Frontiers in oncology · 2021Review
- Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Topical 2'-Hydroxyflavanone for Cutaneous Melanoma.Cancers · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 11 institutions in 1 country.
Funding
Abstract
backgroundInterleukin 2 (IL-2) is a growth factor for T and natural killer cells, promotes proinflammatory cytokines, and can lead to durable responses in patients with melanoma. Vascular endothelial growth factor (VEGF) promotes angiogenesis and modulates host innate and adaptive immunity. High VEGF levels were found to be associated with nonresponse to IL-2. Ziv-aflibercept may deplete VEGF and thereby enhance antitumor T-cell responses, thus supporting a combination immunotherapeutic strategy with IL-2.
methodsNCI 8628 was a phase 2 trial of ziv-aflibercept and IL-2 (arm A) versus IL-2 alone (arm B) randomized at 2:1, respectively. Eligible patients had inoperable American Joint Committee on Cancer stage III or stage IV melanoma. The primary endpoint was progression-free survival (PFS).
resultsA total of 89 patients were enrolled and 84 patients were treated. The median follow-up was 41.4 months. Among treated patients (55 patients in arm A and 29 patients in arm B), PFS was significantly improved in favor of arm A, with a median of 6.9 months (95% confidence interval [95% CI], 4.1-8.7 months) versus 2.3 months (95% CI, 1.6-3.5 months) (P<.001). No significant difference was noted with regard to overall survival, with a median of 26.9 months (95% CI, 14.4-63.6 months) for arm A and 24.2 months (95% CI, 11.3-36.4 months) for arm B. The response rate (according to Response Evaluation Criteria In Solid Tumors [RECIST]) was 22% in arm A (4 complete responses [CRs] and 8 partial responses [PRs]) and 17% in arm B (1 CR and 4 PRs). Stable disease or PR or CR was noted in 65% of patients in arm A and 48% of patients in arm B. The combination was found to be superior to monotherapy in patients with high and low levels of serum VEGF and VEGF receptor 2. Adverse events were consistent with the expected profiles of monotherapy with IL-2 and ziv-aflibercept.
conclusionsZiv-aflibercept and IL-2 were found to significantly improve PFS compared with IL-2 alone, thereby meeting the primary endpoint of the current study. These findings support further study of immunotherapeutic combination strategies involving VEGF inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.