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| Ref Type | Journal Article | ||||||||||||
| PMID | (39453771) | ||||||||||||
| Authors | Aokage K, Koyama S, Kumagai S, Nomura K, Shimada Y, Yoh K, Wakabayashi M, Fukutani M, Furuya H, Miyoshi T, Tane K, Samejima J, Taki T, Hayashi T, Matsubayashi J, Ishii G, Nishikawa H, Ikeda N, Tsuboi M | ||||||||||||
| Title | Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1-Positive NSCLC: A Phase II Trial (EAST ENERGY). | ||||||||||||
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| Abstract Text | Angiogenesis inhibitors are known to modify tumor immunity. Combination of angiogenesis inhibitors with immune checkpoint inhibitors has shown efficacy against many types of cancers, including non-small cell lung cancer (NSCLC). We investigated the feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab, a VEGFR-2 antagonist for patients with PD-L1-positive NSCLC, and its influence on the tumor microenvironment.Patients with pathologically proven, PD-L1-positive, clinical stage IB to IIIA NSCLC were eligible. Patients received two cycles of pembrolizumab (200 mg/body) and ramucirumab (10 mg/kg) every 3 weeks. Surgery was scheduled 4 to 8 weeks after the last dose. The primary endpoint was the major pathologic response rate by a blinded independent pathologic review. The sample size was 24 patients. Exploratory endpoints were evaluated to elucidate the effects of neoadjuvant therapy on the tumor microenvironment.The 24 eligible patients were enrolled between July 2019 and April 2022. The major pathologic response rate was 50.0% (90% confidence interval, 31.9%-68.1%). Six patients showed pathologic complete response. Grade 3 adverse events (AE) occurred in nine patients (37.5%), including three immune-related AEs (acute tubulointerstitial nephritis in two cases and polymyalgia rheumatica in one case). There were no grade 4 or 5 AEs. The transcriptome and multiplex IHC results suggested that tumors with greater CD8+ T-cell infiltration and higher expression of effector molecules at the baseline could show better sensitivity to treatment.This new neoadjuvant combination of pembrolizumab plus ramucirumab was feasible, and anti-VEGF agents may enhance the effects of immune checkpoint inhibitors. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| CD274 positive | lung non-small cell carcinoma | predicted - sensitive | Pembrolizumab + Ramucirumab | Phase II | Actionable | In a Phase II trial (EAST ENERGY), neoadjuvant treatment with Cyramza (ramucirumab) plus Keytruda (pembrolizumab) demonstrated safety and activity in patients with CD274 (PD-L1)-positive (IHC>=1%) non-small cell lung cancer, with a major pathologic response rate of 50.0% (12/24), pathologic complete response rate of 25.0% (6/24), objective response rate of 29.2% (7/24, all partial responses), 2-year overall survival rate of 95.7%, and 2-year relapse-free survival rate of 82.6% (PMID: 39453771; NCT04040361). | 39453771 |