scholarly journals Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO)

Immunotherapy ◽  
2021 ◽  
Author(s):  
Jacob M Sands ◽  
Sumithra J Mandrekar ◽  
David Kozono ◽  
Geoffrey R Oxnard ◽  
Shauna L Hillman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Small Cell ◽  
Disease Stage ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Biomarker Analysis

Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study that will evaluate both concurrent chemotherapy plus pembrolizumab and sequential chemotherapy followed by pembrolizumab to standard of care adjuvant platinum-based chemotherapy. Clinical trial registration: NCT04267848 (ClinicalTrials.gov)

Toxicities associated with checkpoint inhibitor immunotherapy: The Karmanos Cancer Center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14575-e14575
Author(s):  
Misako Nagasaka ◽  
Roba S Alhasan ◽  
Marcus Crosby ◽  
Nithin Thummala ◽  
Seongho Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Standard Of Care ◽  
Small Cell ◽  
Categorical Variables ◽  
Small Cell Lung

e14575 Background: PD-1 inhibitors work by re-instating the natural anti-cancer immune-mediated cytotoxicity. Although this new class of therapy offers hope for many advanced stage cancer patients (pts), data on pts who are more likely to experience adverse events (AE) are not available. Methods: Data from pts who received at least one dose of PD-1 inhibitors before August 31, 2016, were captured from our institution’s pharmacy database. AE of anemia, neutropenia, thrombocytopenia, acute kidney injury, hypothyroidism, transaminitis, pneumonitis, colitis and fatigue were recorded and graded based on CTCAEv4. Baseline pt characteristics were statistically compared between subjects who received PD-1 inhibitors on a clinical trial vs as part of standard of care (on vs. off-study) by Fisher’s exact test for categorical variables and Kruskal-Wallis test for continuous variables. Univariable and multivariable logistic regression models were fit to assess associations between toxicities (Grade0-1 vs. Grade2+) and predictors (age, agent, primary tumor, and trial status). Results: 231 pts received at least one dose of PD-1 inhibitors prior to data cut-off. Median age was 65 (24-92) off trial (n = 125) and 59. 5 (25-79) on trial (n = 106). There were 117 (51%) non-small cell lung cancer (NSCLC), 41 (18%) renal cell carcinoma (RCC) and 73 (32%) others. 24 (10%) melanoma, 18 (8%) Hodgkin’s lymphoma (HL), 9 (4%) head and neck squamous cell carcinoma (HNSCC), 8 (4%) small cell lung cancer (SCLC) were included in others. 129 (56%) had nivolumab alone, 50 (22%) had pembrolizumab alone and the rest 52 (23%) received combination treatment. Pts participating in a clinical trial had higher odds to experience grade 2 or more pneumonitis than those not on a trial (unadjusted p = 0.038). On trial pts had lower odds to experience grade 2 or more fatigue than those receiving the agent as standard of care (unadjusted p = 0.026) which remained significant after adjusting age, agent (single agent vs combination) and primary tumor (adjusted p = 0.004). Conclusions: In our observation, pneumonitis was seen more on clinical trials whereas fatigue was seen less.

scholarly journals Immunotherapy In Advanced Lung Cancer

ONCOLOGY ◽  
2020 ◽  
pp. 272-279
Author(s):  
Joy Huang ◽  
Karen Reckamp
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Single Agent ◽  
Standard Of Care ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

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 inhibitors with platinum-based chemotherapy has become the new standard of care for patients with advanced NSCLC. Furthermore, in ES SCLC, in which chemotherapy or chemoradiation has been the standard of care for decades, 2 anti–PD-1/PD-L1 agents have been approved for use in the frontline setting for ES SCLC, in combination with chemotherapy. Despite progressive integration of immunotherapy into treatment regimens, there remains a need for reliable biomarkers to precisely determine therapy candidates.

scholarly journals Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier

Radiation ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 317-333
Author(s):  
Tzen S. Toh ◽  
Benjamin H. Lok
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Initial Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Current Standard ◽  
Limited Stage ◽  
Platinum Based Chemotherapy

Limited-stage (LS) small-cell lung cancer (SCLC) is defined as disease confined to a tolerable radiation portal without extrathoracic metastases. Despite clinical research over two decades, the prognosis of LS-SCLC patients remains poor. The current standard of care for LS-SCLC patients is concurrent platinum-based chemotherapy with thoracic radiotherapy (RT). Widespread heterogeneity on the optimal radiation dose and fractionation regimen among physicians highlights the logistical challenges of administering BID regimens. Prophylactic cranial irradiation (PCI) is recommended to patients following a good initial response to chemoradiation due to improved overall survival from historical trials and the propensity for LS-SCLC to recur with brain metastases. However, PCI utilization is being debated due to the greater availability of magnetic resonance imaging (MRI) and data in extensive-stage SCLC regarding close MRI surveillance in lieu of PCI while spurring novel RT techniques, such as hippocampal-avoidance PCI. Additionally, novel treatment combinations incorporating targeted small molecule therapies and immunotherapies with or following radiation for LS-SCLC have seen recent interest and some concepts are being investigated in clinical trials. Here, we review the landscape of progress, limitations, and challenges for LS-SCLC including current standard of care, novel radiation techniques, and the integration of novel therapeutic strategies for LS-SCLC.

Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists

2020 ◽  
Vol 16 (1) ◽  
pp. 5-10
Author(s):  
Adrien Costantini ◽  
Theodoros Katsikas ◽  
Clementine Bostantzoglou
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Genetic Alterations ◽  
Small Cell ◽  
Extensive Literature ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Mutational Status

Over the past decade, major breakthroughs in the understanding of lung cancer histology and mutational pathways have radically changed diagnosis and management. More specifically, in non-small cell lung cancer (NSCLC), tumour characterisation has shifted from differentiating based solely on histology to characterisation that includes genetic profiling and mutational status of Epidermal Growth Factor (EGFR), Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF. These genetic alterations can be targeted by specific drugs that result in improved progression-free survival, as well as higher response rates and are currently standard of care for NSCLC patients harbouring these mutations. In this a narrative, non-systematic review we aim to handpick through the extensive literature and critically present the ground-breaking studies that lead to the institution of tailored treatment options as the standard of care for the main targetable genetic alterations.

scholarly journals Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genome Instability ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Levels ◽  
Platinum Based Chemotherapy ◽  
Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

scholarly journals Polymorphisms in the Gene Encoding Caspase 8 May Predict the Response to First-Line Platinum-Based Chemotherapy in Locally Advanced or Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Small Cell ◽  
Caspase 8 ◽  
Small Cell Lung ◽  
Gene Encoding ◽  
Platinum Based Chemotherapy

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).

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