Pembrolizumab in advanced pretreated small cell lung cancer patients with PD-L1 expression: data from the KEYNOTE-028 trial: a reason for hope?

Navarro, Alejandro; Felip, Enriqueta

doi:10.21037/tlcr.2017.10.04

Cited by 7 publications

(5 citation statements)

References 19 publications

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“…Recently, a number of immunotherapies—specifically, different types of programmed cell death inhibitors—have received approval by the US Food & Drug Administration (FDA) for different indications across a wide range of tumor types . The recent successes of immunotherapy in the treatment of other cancer types suggest that immunotherapies may provide a clinical benefit that has not yet been achieved for SCLC patients by traditional chemotherapy treatments .…”

Section: Introductionmentioning

confidence: 99%

“…6 Recently, a number of immunotherapies-specifically, different types of programmed cell death inhibitors-have received approval by the US Food & Drug Administration (FDA) for different indications across a wide range of tumor types. 11 The recent successes of immunotherapy in the treatment of other cancer types suggest that immunotherapies may provide a clinical benefit that has not yet been achieved for SCLC patients by traditional chemotherapy treatments. 8 In 2018 nivolumab was approved for metastatic SCLC after disease progression following platinum-based therapy and at least one other line of therapy; and in 2019 atezolizumab plus carboplatin and etoposide was approved for 1L therapy among patients with extensive-stage SCLC.…”

Section: Introductionmentioning

confidence: 99%

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Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER‐Medicare study

et al. 2019

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Objectives The effectiveness and costs of new treatments should be assessed in relation to existing practice. We describe treatments, survival and costs for advanced or metastatic small cell lung cancer (SCLC) patients receiving systemic therapy in the period preceding the introduction of immunotherapies. Materials and Methods This was a retrospective cohort study of patients aged ≥65 years, identified using linked Surveillance, Epidemiology, and End Results and Medicare databases. Individuals with a new primary diagnosis of SCLC between January 2007 and December 2013 were followed until December 2014. Chemotherapy treatments, health care visits and costs (in 2016 USD), and survival were determined by line of therapy. Results A total of 11 812 patients were identified with SCLC. First‐line (1L) chemotherapy was received by 6509 (55.1%) patients, most (93.2%) with carboplatin‐ (71.0%) or cisplatin‐ (22.2%) based therapies, typically combined with etoposide (79.2%). Second‐ (2L) and third‐ (3L) line chemotherapies were received by 2238 (18.9%) and 679 (5.7%) patients, of which 48.4% and 30.9%, respectively, were platinum‐based. The median durations of 1L, 2L, and 3L carboplatin‐based therapies were 5.9, 4.8, and 5.4 months, respectively, and the corresponding durations of cisplatin‐based therapies were 5.3, 4.2, and 5.3 months. During 1L, 2L, and 3L chemotherapies, patients averaged 8.2, 7.4, and 7.3 health care visits per month, respectively, and incurred total mean health care costs of $60 223, $42 636, and $35 903 per patient, respectively. Median survival from the start of 1L, 2L, and 3L chemotherapy was 9.2, 6.0, and 5.7 months, respectively. Conclusion First‐line chemotherapy was primarily platinum‐based, and a plethora of different regimens was used for 2L and 3L chemotherapies. Median survival from the start of 1L chemotherapy was 9 months, with an associated health care cost of $60 000. These data highlight an unmet medical need among SCLC patients receiving systemic therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER‐Medicare study

et al. 2019

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“…Immunotherapy using checkpoint inhibitors such as Pembrolizumab, which is a humanized monoclonal antibody that binds the PD-1 receptor, and Nivolumab, which is a fully human PD-1 immune checkpoint inhibitor antibody, has shown promising medicinal effects by modulating the immune microenvironment in SCLC [ 80 , 81 ]. Furthermore, combinations of chemotherapy and immunotherapy and other treatment, such as SRA737 plus low dose gemcitabine with anti-PD1 antibody, have currently been in clinical trials for SCLC and other malignancies [ 82 ].…”

Section: Sclc Splicing Variant Dx2 and Target Moleculesmentioning

confidence: 99%

Splicing Variants, Protein-Protein Interactions, and Drug Targeting in Hutchinson-Gilford Progeria Syndrome and Small Cell Lung Cancer

Kim¹,

Woo²,

Kang

et al. 2022

Genes

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Alternative splicing (AS) is a biological operation that enables a messenger RNA to encode protein variants (isoforms) that give one gene several functions or properties. This process provides one of the major sources of use for understanding the proteomic diversity of multicellular organisms. In combination with post-translational modifications, it contributes to generating a variety of protein–protein interactions (PPIs) that are essential to cellular homeostasis or proteostasis. However, cells exposed to many kinds of stresses (aging, genetic changes, carcinogens, etc.) sometimes derive cancer or disease onset from aberrant PPIs caused by DNA mutations. In this review, we summarize how splicing variants may form a neomorphic protein complex and cause diseases such as Hutchinson-Gilford progeria syndrome (HGPS) and small cell lung cancer (SCLC), and we discuss how protein–protein interfaces obtained from the variants may represent efficient therapeutic target sites to treat HGPS and SCLC.

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“…However, PD-L1 interpretation can be difficult due to intratumoural heterogeneity, dynamic changes and different testing methods with different cut-off thresholds, which hinders cross-trial comparison and data validation. 36 , 37 , 38 …”

Section: Predictive Biomarkersmentioning

confidence: 99%

First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

Ortega-Franco

Ackermann²,

Paz‐Ares

et al. 2021

ESMO Open

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Pembrolizumab in advanced pretreated small cell lung cancer patients with PD-L1 expression: data from the KEYNOTE-028 trial: a reason for hope?

Abstract: Spain).Comment on: Ott PA, Elez E, Hiret S, et al. Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study.

Cited by 7 publications

References 19 publications

Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER‐Medicare study

Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER‐Medicare study

Splicing Variants, Protein-Protein Interactions, and Drug Targeting in Hutchinson-Gilford Progeria Syndrome and Small Cell Lung Cancer

First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

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