A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor (TKI) naïve patients with advanced NSCLC.

Lisberg, Aaron; Cummings, Amy L.; Goldman, Jonathan W.; Bornazyan, Krikor; Reese, Nicholas; Wang, Tina; Coluzzi, Paul; Ledezma, Blanca; Mendenhall, Melody; Jones, Benjamin; Madrigal, John; Carroll, James M.; Gukasyan, Jaklin; Williams, Tawny; Sauer, Lauren; Wells, Courtney; Hardy, Ariana; Linares, Paulina; Adame, Carlos; Garon, Edward B.

doi:10.1200/jco.2018.36.15_suppl.9014

Cited by 12 publications

(18 citation statements)

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“…The covariates other than MPE were adopted based on the results of recent trials suggesting that they might affect the efficacy of PD-1/PD-L1 checkpoint inhibitors. 1,11,[13][14][15]17,19,20 All P values were based on a one-sided hypothesis, and values < 0.05 were considered statistically significant. All statistical analyses were performed using JMP Pro version 13.0.0 (SAS Institute, Cary, NC, USA).…”

Section: Discussionmentioning

confidence: 99%

“…Univariate and multivariate analyses were performed using Cox proportional hazard regression models for performance status, smoking status, EGFR mutational status, PD‐L1 expression status, treatment line, and the presence of MPE. The covariates other than MPE were adopted based on the results of recent trials suggesting that they might affect the efficacy of PD‐1/PD‐L1 checkpoint inhibitors . All P values were based on a one‐sided hypothesis, and values < 0.05 were considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

“…EGFR mutation, a never-smoker status, and a poor performance status (PS) were all correlated with a lower efficacy of PD-1/PD-L1 checkpoint inhibitors, compared to EGFR wild-type, smoker status, and a good PS, respectively. [10][11][12][13][14][15] A previous study also reported that the presence of liver or lung metastases was a negative predictor of anti-PD-1 efficacy in patients with advanced NSCLC. However, no previous reports have compared the efficacy of anti-PD-1 antibodies between NSCLC patients with and without MPE.…”

Section: Introductionmentioning

confidence: 93%

“…Several studies have shown that the efficacy of PD‐1/PD‐L1 checkpoint inhibitors is correlated with several patient characteristics. EGFR mutation, a never‐smoker status, and a poor performance status (PS) were all correlated with a lower efficacy of PD‐1/PD‐L1 checkpoint inhibitors, compared to EGFR wild‐type, smoker status, and a good PS, respectively . A previous study also reported that the presence of liver or lung metastases was a negative predictor of anti‐PD‐1 efficacy in patients with advanced NSCLC.…”

Section: Introductionmentioning

confidence: 94%

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Malignant pleural effusion as a predictor of the efficacy of anti‐PD‐1 antibody in patients with non‐small cell lung cancer

Shibaki¹,

Murakami²,

Shinno³

et al. 2019

Thoracic Cancer

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Background The aim of this study was to evaluate the usefulness of the presence of malignant pleural effusion (MPE) as a negative predictor of anti‐PD‐1 antibody efficacy. Methods A retrospective review of patients with advanced or recurrent non‐small cell lung cancer treated with an anti‐PD‐1 antibody between December 2015 and March 2018 at the National Cancer Center Hospital, Japan, was conducted. Progression‐free survival (PFS) and overall survival (OS) were compared between patients with and without MPE. Additional survival analysis according to PD‐L1 expression status was conducted. Univariate and multivariate analyses were performed. Results A total of 252 patients were identified before the commencement of anti‐PD‐1 antibody treatment: 33 with MPE and 219 without MPE. PFS and OS were significantly shorter in patients with MPE than in patients without MPE (median PFS 3.0 vs. 5.8 months, hazard ratio [HR] 1.7, P = 0.014; median OS 7.9 vs. 15.8 months, HR 2.1, P = 0.001). In patients with PD‐L1 expression in ≥ 1% of their tumor cells, the PFS of patients with MPE was significantly shorter than of patients without MPE (median PFS 3.1 vs. 6.5 months, HR 2.0, 95% confidence interval 1.0–3.5; P = 0.021). The presence of MPE was independently associated with a shorter PFS and OS in multivariate analysis. Conclusion The presence of MPE in patients administered an anti‐PD‐1 antibody is associated with shorter PFS and OS, regardless of the presence of PD‐L1 expression ≥ 1% of tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 94%

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Malignant pleural effusion as a predictor of the efficacy of anti‐PD‐1 antibody in patients with non‐small cell lung cancer

Shibaki¹,

Murakami²,

Shinno³

et al. 2019

Thoracic Cancer

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“…Significance was maintained within the nonsquamous subset ( n = 249) . Pembrolizumab lacks efficacy in TKI‐naive patients with EGFR mutations . Recent results from the KEYNOTE‐042 trial confirm OS benefits with pembrolizumab in patients with PD‐L1 expression levels ≥1% (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.71–0.93; p = .0018) .…”

Section: Nsclc Treatment Paradigmmentioning

confidence: 99%

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non-Small Cell Lung Cancer: A Review

Karim

Kelly

2019

The Oncologist

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Advanced non‐small cell lung cancer (NSCLC) is a complex disease comprising molecularly distinct tumor types, each with a unique biology that is becoming increasingly better characterized. The aim of this review is to present an optimized treatment schema and the accompanying diagnostic testing approach for patients with advanced NSCLC. There are a number of therapies currently approved for patients with advanced NSCLC, including agents that target particular oncogenic drivers, as well as immune checkpoint blockers (ICBs) that elicit an antitumor response. Identification of genetic alterations (e.g., epidermal growth factor receptor, anaplastic lymphoma kinase, reactive oxygen species proto‐oncogene 1, B‐Raf proto‐oncogene) or programmed cell death ligand‐1 expression levels in NSCLC requires diligent molecular testing at initial diagnosis and, in some cases, at disease progression to ensure the most efficacious treatment is delivered. Accurate molecular diagnostic testing, along with the careful selection of currently approved targeted agents, ICBs, or systemic chemotherapy, provides therapy that is personalized according to patients’ needs to achieve the best possible outcome. Enrollment in clinical trials that further the development of tailored therapies is highly recommended at all stages of treatment. Implications for Practice Targeted therapies and immune checkpoint blockers provide effective and tailored options for patients with non‐small cell lung cancer. Careful molecular analysis of tumor samples is necessary to identify the genetic alterations that are present, to ensure that each patient receives the most efficacious treatment for their specific tumor type. Personalized therapy provides each patient with the best probability for prolonged survival. Enrolling patients in clinical trials should be the first consideration before making each treatment decision.

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Immune checkpoint inhibitor‐associated pituitary‐adrenal dysfunction: A systematic review and meta‐analysis

Lü

Lan

et al. 2019

Cancer Medicine

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With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life‐threatening pituitary‐adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary‐adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta‐analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%‐3.22%) for all‐grade adrenal insufficiency and 3.25% (95% CI, 2.15%‐4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious‐grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious‐grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI‐based treatment, particularly for CTLA‐4 inhibitors, which were associated with a higher incidence of pituitary‐adrenal dysfunction than PD‐1/PD‐L1 inhibitors.

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A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor (TKI) naïve patients with advanced NSCLC.

Cited by 12 publications

References 0 publications

Malignant pleural effusion as a predictor of the efficacy of anti‐PD‐1 antibody in patients with non‐small cell lung cancer

Malignant pleural effusion as a predictor of the efficacy of anti‐PD‐1 antibody in patients with non‐small cell lung cancer

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non-Small Cell Lung Cancer: A Review

Immune checkpoint inhibitor‐associated pituitary‐adrenal dysfunction: A systematic review and meta‐analysis

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