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November 1993 - present
Publications
Publications (1,116)
Background: Small cell lung cancer (SCLC), extra-pulmonary neuroendocrine carcinomas (epNECs) and large cell NECs (LCNECs) of the lung are difficult-to-treat, aggressive tumors with limited treatment (Tx) options. Standard of care for metastatic disease is platinum-based chemotherapy ± immunotherapy. However, nearly all patients (pts) relapse, and...
Background
In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemot...
PURPOSE
The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.
METHODS
Patients received t...
ZUSAMMENFASSUNG
Die Identifikation Biomarker-stratifizierter Behandlungen hat das Überleben eines relevanten Anteils an Patient*innen mit metastasiertem Lungenkrebs in den letzten Jahren teils erheblich verbessert. Hierzu zählen Treibermutationen und bei Treiber-negativen Tumoren die Expression des „programmed death ligand 1“ (PD-L1) hinsichtlich d...
PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tu...
Background
The phase 3 IMpower150 trial showed significantly improved progression-free survival (PFS) and overall survival (OS) with atezolizumab plus bevacizumab plus carboplatin-paclitaxel (ABCP) versus bevacizumab plus carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with non-squamous metastatic NSCLC, regardless of tumor PD-L1 status...
Background
Tumor samples from the phase III IMpower010 study were used to compare two programmed death-ligand 1 (PD-L1) immunohistochemistry assays (VENTANA SP263 and Dako 22C3) for identification of PD-L1 patient subgroups (negative, positive, low, and high expression) and their predictive value for adjuvant atezolizumab compared with best support...
Zusammenfassung
Die aktuelle Fassung der Leitlinie Lungenkarzinom trägt der Dynamik der Informationen in diesem Fachbereich Rechnung. Insbesondere gelten folgenden Empfehlungen:
Die Vorstellung aller neu diagnostizierten Patienten im interdisziplinären pneumoonkologischen Tumorboard ist verpflichtend, das CT-Screening für asymptomatische Risikopers...
Background:
Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.
Methods:
We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of...
Background:
Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer.
Methods:
In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every...
Introduction
Studies have shown improved tolerability with once-weekly versus three-weekly docetaxel in the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the tolerability of nintedanib plus weekly docetaxel in patients with NSCLC.
Methods
This phase I, open-label, dose-escalation study (NCT02668...
Background
Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) d...
Zusammenfassung
Die Identifikation Biomarker-stratifizierter Behandlungen hat das Überleben eines relevanten Anteils an Patient*innen mit metastasiertem Lungenkrebs in den letzten Jahren teils erheblich verbessert. Hierzu zählen Treibermutationen und bei Treiber-negativen Tumoren die Expression des „programmed death ligand 1“ (PD-L1) hinsichtlich d...
PURPOSE
To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2–positive (HER2+) metastatic biliary tract cancer (mBTC).
METHODS
SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380 ) is an open-label phase II basket study evaluating the efficacy and safety of...
Purpose:
Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal gr...
Introduction
In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy....
Background:
Patients with non-small cell lung cancer (NSCLC) and stable disease (SD) have an unmet clinical need to help guide early treatment adjustments.
Objective:
To evaluate the potential of tumor biomarkers to inform on survival outcomes in NSCLC SD patients.
Methods:
This post hoc analysis included 480 patients from the IMpower150 study...
Introduction:
Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking PD-L1, has shown clinical activity in a phase 1 expansion cohort of patients with PD-L1-high, advanced non-small cell lung cancer (NSCLC).
Methods:
This a...
Therapeutic strategies harnessing the immune system to eliminate tumour cells have been successfully used for several cancer types, including in patients with advanced-stage non-small-cell lung cancer (NSCLC). In these patients, immune-checkpoint inhibitors (ICIs) can provide durable responses and improve overall survival either as monotherapy, or...
Background
Lung cancer remains the deadliest cancer in the world and survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography (LDCT) screening can significantly reduce mortality, however, annual screening is limited by low adherence in the USA and still not broadly implemented in Europe. As a result, <10%...
Background:
Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line...
Background:
IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab vs best supportive care (BSC) following platinum-based chemotherapy in the PD-L1-positive and all stage II-IIIA non-small cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim ana...
Background:
Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identif...
Background:
Despite promising results of targeted therapy approaches, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Tripartite motif containing 11 (TRIM11) is part of the TRIM family of proteins, playing crucial roles in tumor progression. TRIM11 serves as an oncogene in various cancer types and has been rep...
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand...
LBA9023
Background: In CheckMate 9LA (NCT03215706), 1L N + I + C demonstrated durable survival benefit in pts with mNSCLC vs C alone. Here, we report updated efficacy and safety with a 4-y minimum (min) follow-up (f/u) as well as exploratory analyses of efficacy by THS, a known prognostic indicator for NSCLC. Methods: Adults with stage IV/recurrent...
Background:
Approximately 21 900 women and 35 300 men developed lung cancer in Germany in 2018, and 16 999 women and 27 882 men died of it. The outcome mainly depends on the tumor stage. In early stages (stage I or II), treatment can be curative; unfortunately, because early-stage lung cancers are generally asymptomatic, 74% of women and 77% of me...
TPS8611
Background: Small cell lung cancer (SCLC) is an aggressive malignancy for which very few patients achieve long term disease control; response to most treatments is transient and second line treatment options are limited. Delta-like ligand 3 (DLL3) is a Notch ligand aberrantly expressed on the surface of up to 85% of SCLC cells and minimally...
TPS8613
Background: Lurbinectedin is a novel synthetic chemical entity that acts as an inhibitor of oncogenic transcription and is active in tumors addicted to transcription. A phase II Basket trial (NCT02454972) in patients with small cell lung cancer (SCLC) treated with lurbinectedin in the second-line setting showed overall response rate (ORR) o...
TPS8601
Background: Pleural mesothelioma (PM) is a highly aggressive cancer of the pleura, predominantly caused by prior asbestos exposure. Currently, there is no approved standard therapy for the treatment of early-stage PM. In most cases a multimodal therapy is recommended consisting of locoregional treatment by surgical cytoreduction via extende...
8522
Background: The Phase III IMpower010 trial (NCT02486718) met its primary disease-free survival (DFS) endpoint leading to approval of atezolizumab after adjuvant platinum-based chemotherapy for completely resected PD-L1 TC ≥1% or ≥50% stage II-IIIA NSCLC in the US, EU and other regions. Mutant KRAS (mKRAS) is the most prevalent oncogenic driver...
3035
Background: Low-dose computed tomography (LDCT) screening can significantly reduce lung cancer mortality. However, annual screening is limited by low adherence in the USA and still not broadly implemented in Europe. As a result, <10% of lung cancers are detected through existing programs. Thus, there is great need for additional diagnostic mod...
9099
Background: PERLA (NCT04581824) is a global, randomized, Phase II, double-blind study assessing the efficacy and safety of chemotherapy (CT) combined with programmed death 1 (PD-1) inhibitors dostarlimab (dostCT) and pembrolizumab (pembCT) as first-line (1L) treatment (tx) for patients (pts) with metastatic non-oncogene-driven, non-squamous, N...
4007
Background: Biliary tract cancer (BTC) is an aggressive malignancy with a poor prognosis, and current treatment options for advanced BTC are limited, with second-line therapy, FOLFOX and S-1 offering an objective response rate (ORR) of 5.0% and 7.5%, respectively. Up to 20% of BTCs overexpress human epidermal growth factor receptor 2 (HER2). T...
TPS9141
Background: Although immune checkpoint inhibitors have improved clinical outcomes in mNSCLC, the majority of patients will experience progression and shorter survival. Thus, an urgent need exists for more effective treatment options in mNSCLC. DOM is an anti-TIGIT IgG1, Fc-silent monoclonal antibody designed to inhibit the interaction betwe...
Pembrolizumab monotherapy is a standard first-line treatment for PD-L1–high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface anti...
Background: Recent trials have demonstrated the clinical benefit of immunotherapy in either the neoadjuvant or adjuvant resectable (R) NSCLC setting. AEGEAN (NCT03800134) is a randomized, double-blind, placebo (PBO)-controlled trial assessing neoadjuvant durvalumab (D) + chemotherapy (CT) followed by surgery (Sx) and adjuvant D in patients (pts) wi...
Limited treatment options exist for EGFR-mutated NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy. HER3 is highly expressed in EGFR-mutated NSCLC, and its expression is associated with poor prognosis in some patients. Patritumab deruxtecan (HER3-DXd) is an investigational, potential first-in-class, HER3-directed antibody-dru...
Introduction:
In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC), regardless of tumor programmed death ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic/intracranial efficacy outcomes and safety by baseline b...
Background
Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis...
Zusammenfassung
Die Identifikation Biomarker-stratifizierter Behandlungen hat das Überleben eines relevanten Anteils an Patient*innen mit metastasiertem Lungenkrebs in den letzten Jahren teils erheblich verbessert. Hierzu zählen Treibermutationen und bei Treiber-negativen Tumoren die Expression des „programmed death ligand 1“ (PD-L1) hinsichtlich d...
Background: Standard therapies for patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) that has progressed after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs) offer only limited benefit. Human epidermal growth factor receptor 3 (HER3) is often expressed in primary NSCLC tumors,...
Background:
In CheckMate 9LA (NCT03215706), first-line nivolumab plus ipilimumab with chemotherapy (2 cycles) significantly improved overall survival versus chemotherapy (4 cycles) in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor/anaplastic lymphoma kinase alterations. We present expl...
Introduction:
Pemetrexed-based immunochemotherapy represents an established standard of care as first line treatment for non-oncogenic driven metastatic non-small cell lung adenocarcinoma (NSCLC/ADC). However, retrospective analyses revealed better outcomes for pemetrexed-free regimens compared to pemetrexed-containing regimens in patients with th...
Alternative sources of tumor information need to be explored in patients with non-small cell lung cancer (NSCLC). Here, we compared programmed cell death 1 ligand 1 (PD-L1) expression on cytology imprints and circulating tumor cells (CTCs) with PD-L1 tumor proportion score (TPS) from immunohistochemistry staining of tumor tissue from patients with...
One of the great challenges in therapeutic oncology is determining who might achieve survival benefits from a particular therapy. Studies on longitudinal circulating tumor DNA (ctDNA) dynamics for the prediction of survival have generally been small or nonrandomized. We assessed ctDNA across 5 time points in 466 non-small-cell lung cancer (NSCLC) p...
The implementation of immune checkpoint inhibitors (ICIs), with or without chemotherapy, as first-line treatment for patients who do not have actionable mutations has proved to be a major paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). However, the transition of ICIs, such as pembrolizumab and nivolumab, to a first-...
Background:
Ramucirumab plus erlotinib (RAM+ERL) demonstrated superior progression-free survival (PFS) in RELAY, a randomised Phase III trial in patients with untreated, metastatic, EGFR-mutated, non-small-cell lung cancer (EGFR+ NSCLC). Here, we present the relationship between TP53 status and outcomes in RELAY.
Materials and methods:
Patients...
Leveraging real-world data (RWD) for drug access is necessary to overcome a key challenge of modern precision oncology: tackling numerous low-prevalence oncogenic mutations across cancers. Withholding a potentially active medication in patients with rare mutations for the sake of control chemotherapy or "best" supportive care is neither practicable...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published...
Importance:
Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes.
Objective:
To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies.
Desig...
Although immunotherapy (IO) has changed the paradigm for the treatment of patients with advanced non-small cell lung cancers (aNSCLC), only around 30% to 50% of treated patients experience a long-term benefit from IO. Furthermore, the identification of the 30 to 50% of patients who respond remains a major challenge, as programmed Death-Ligand 1 (PD...
Introduction:
Trials of CT-based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population.
Methods:
We used data from 3623 lung cancer...
Purpose:
Model-based tumor growth inhibition (TGI) metrics are increasingly incorporated into go/no-go decisions in early clinical studies. To apply this methodology to new investigational combinations requires independent evaluation of TGI metrics in recently completed Phase III trials of effective immunotherapy.
Methods:
Data were extracted fr...
Background
DNA methylation (5-mC) signals in cell-free DNA (cfDNA) of cancer patients represent promising biomarkers for minimally invasive tumor detection. The high abundance of cancer-associated 5-mC alterations permits parallel and highly sensitive assessment of multiple 5-mC biomarkers. Here, we performed genome-wide 5-mC profiling in the plasm...
Immunotherapies have recently gained traction as highly effective therapies in a subset of late-stage cancers. Unfortunately, only a minority of patients experience the remarkable benefits of immunotherapies, whilst others fail to respond or even come to harm through immune-related adverse events. For immunotherapies within the PD-1/PD-L1 inhibitor...
Background
Extensive-stage (ES) small cell lung cancer (SCLC) disproportionately contributes to annual lung cancer-related deaths.1,2,3 Following the pivotal Phase III IMpower133 study, the PD-L1 inhibitor atezolizumab, combined with carboplatin and etoposide (CE), was the first immune checkpoint inhibitor approved for first-line treatment of ES-SC...
Purpose/Objective(s)
Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) + cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; no...
Introduction
We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab-combination for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials.
Methods
This retrosp...
Objectives
For refractory NSCLC patients with EGFR mutations, recent studies have demonstrated a favorable response to the combination of anti-angiogenic therapy and checkpoint inhibition but included only very few patients with uncommon EGFR mutations for which treatment options are still limited despite new targeted treatments.
Materials and Met...
Background
First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced NSCLC. We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
Patients and methods
Data were pooled from four studies of first-line nivolumab plus ipilimumab in...
