Immune Checkpoint Inhibitors in NSCLC

Opinion statement Lung cancer is the leading cause of cancer-related mortality worldwide. Cytotoxic chemotherapy and tyrosine kinase inhibitors provide palliation and prolong survival, however, the median survival for patients with metastatic disease remains poor and more effective therapies are needed. Immune checkpoint inhibitors have shown promising results in phase I trials and are being evaluated in ongoing clinical trials in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients. These include agents targeting the programmed cell death-1 receptor and its ligand (PD-1/PD-L1; notably nivolumab, pembrolizumab, MPDL3280A, and MEDI-4736) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; ipilimumab and tremelimumab); these agents induce antitumor responses by inhibiting critical negative T cell regulators. In particular, the anti-PD-1/PD-L1 therapies administered as single agent therapy in chemotherapy refractory patients have produced objective response rates ranging from 15 %–25 %, the majority of which were rapid and ongoing 1 year after starting therapy. Furthermore, the toxicity profile for these agents differs from that of cytotoxic chemotherapy but generally is much better tolerated. Promising biomarkers, particularly tumor expression of PD-L1 and tumor infiltrating lymphocytes, may aid in treatment selection and stratification. Ongoing evaluation is needed to define the most appropriate timing and patient population t...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research

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Basel, 17 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that results from a number of studies across its broad oncology portfolio will be presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which will be held 19-21 September, 2020. Results include data from three phase III studies across the Tecentriq® (atezolizumab) triple-negative breast cancer (TNBC) programme. Central nervous system (CNS) efficacy data from integrated analyses of the pivotal phase II Rozlytrek® STARTRK-2, phase I STARTRK-1, and phase I ALKA-372-001 trials will be presented in addition to re...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
DTX1 rs1732786A>G was associated with better prognosis in patients with early ‐stage non‐small cell lung cancer, in the previous study. DTX1 rs1732786A>G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer. Deltex ‐1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect ofDTX1 rs1732786A  >  G, which is associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC).DTX1 rs1732786A  >...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: BRIEF REPORT Source Type: research
Conclusion TTF-1 expression is an independent predictor of first-line chemotherapy response rate and survival in patients with SCLC, and may become a biomarker to predict the efficacy and prognosis of SCLC. DOI: 10.3779/j.issn.1009-3419.2020.101.27
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
In this study, we reported a case in which an SCLC patient with EGFR exon 19 deletion (19-Del) mutation did not benefit from EGFR-TKIs. Interestingly, the standard treatment strategies for SCLC also failed to control tumor progression. Moreover, we screened 43 SCLC patients in China and found that the frequency of EGFR mutations in Chinese SCLC patients was about 4.65% by next-generation sequencing (NGS). Collectively, this case illustrated a rare subtype of SCLCs which harbored EGFR mutations and was intrinsically resistant to standard treatments and EGFR-TKIs. We also tried to explore the mechanisms underlying drug resis...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Historically, platinum-based chemotherapy was the standard of care for metastatic lung cancer. However, since the success of immune checkpoint inhibitors (ICIs) in melanoma, PD-1/PD-L1 and CTLA-4 immune checkpoint pathways have been established as effective therapies to manage advanced non-small cell lung cancer (NSCLC) and extensive-stage (ES) small cell lung cancer (SCLC). Multiple large-scale randomized clinical trials have analyzed the effects of ICIs in NSCLC, and results of these trials have since translated to the approval of single-agent PD-1/PD-L1 inhibitors, and the combination of PD-1 inhibitor...
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. METHODS: The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. RESULTS: The qRT-PCR analysis showed that t...
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
Opinion statementIn March 2019, the FDA approved the use of the anti-programmed death ligand 1 (PD-L1) antibody atezolizumab, as a first-line treatment option in combination with platinum-etoposide (PE) for patients with extensive stage small cell lung cancer (ED SCLC) based upon the results of the IMpower133 trial. More recently, the FDA approved the anti-PD-L1 antibody durvalumab in March 2020 , also in the frontline setting for SCLC based upon the results of the CASPIAN trial. Both these trials demonstrated a small, but significant overall survival (OS) benefit with the addition of a PD-L1 antibody to standard chemother...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Lung cancer is the leading cause of cancer-related death worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancers and is categorized into two histology types: nonsquamous (NSQ) and squamous (SQ) [2]. Small cell lung cancer (SCLC) is less prevalent than NSCLC and accounts for approximately 15-20% of all lung cancers [2,3]. Strategies for first-line treatment for advanced-stage lung cancer continue to evolve to address the high mortality rate. The FDA has approved combination therapy consisting of chemotherapy plus antibodies targeting either programmed cell death protein-1 (PD-1) or progra...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Immune checkpoint inhibitors (ICIs) are currently used as monotherapy or combination therapy in frontline and subsequent lines for metastatic lung cancer including adenocarcinoma, squamous cell carcinoma, and small cell lung cancer (SCLC) [1 –5]. Furthermore, ICIs before or after surgery showed efficacy in patients with resectable disease, highlighting the potential of ICIs to improve outcomes in these patients and expand the use of ICIs in the neoadjuvant and adjuvant settings [6,7]. Despite higher response rates, longer duration of response, and less toxicity of ICIs compared with chemotherapy, many lung cancer pat...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid growth, early metastasis, and acquired therapeutic resistance. A majority of patients with SCLC have extensive-stage (ES) disease, defined as the presence of metastatic disease outside the hemithorax at first diagnosis. SCLC has been considered “a graveyard for drug development,” with chemotherapy remaining the standard treatment for first- and second-line management until quite recently. In contrast to NSCLC, identifying therapeutic targets in SCLC has been challenging, partly because driver mutations are primarily loss of functio...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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