scholarly journals A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer

2022 ◽  
Author(s):  
Yoshihiro Kondo ◽  
Michihiro Kunishige ◽  
Naoki Kadota ◽  
Yoshio Okano ◽  
Hisanori Machida ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Dose ◽  
Durable Response

Single dose of atezolizumab plus chemotherapy in active psoriasis with advanced non-small cell lung cancer

2021 ◽  
pp. 107815522110388
Author(s):  
Pui Yee Wong ◽  
Soon Hin How ◽  
Irnani Ismail ◽  
Radhiana Hassan
Keyword(s):  
Lung Cancer ◽  
Single Dose ◽  
Autoimmune Disease ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Small Cell ◽  
Small Cell Lung ◽  
Durable Response ◽  
Ideal Approach

Introduction Immunotherapy has been recognized as the standard of care in addition to chemotherapy in the treatment of advanced non-small cell lung cancer. Most immunotherapy trials, however, exclude patients with autoimmune disease owing to concerns of disease exacerbation. Case report We report a case of a patient with advanced non-small cell lung cancer and underlying active psoriasis who experienced a remarkable response, without developing psoriasis flares, following treatment with a single dose of atezolizumab and first-line chemotherapy. Management and outcome The patient remained asymptomatic 10 months since treatment discontinuation, without disease progression, despite having received only a single dose of atezolizumab and six cycles of chemotherapy. Discussion Little is known about the optimum duration required to achieve a durable response with immunotherapy. Patients with autoimmune disease are commonly excluded from immunotherapy trials owing to a higher risk of autoimmune disease flares or immune-related adverse events. The remarkable outcome observed in this case offers some insights into the possible durable response with limited doses of immunotherapy and a safer approach for administering immunotherapy in patients with autoimmune disease. Initiating chemotherapy to induce remission in active autoimmune disease prior to administering immunotherapy could potentially be an ideal approach that facilitates the use of immunotherapy in this patient population.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

scholarly journals Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC)

Cancer ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Holger Hof ◽  
Marc Muenter ◽  
Dieter Oetzel ◽  
Angelika Hoess ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Single Dose ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Nonsmall Cell Lung Cancer

A phase II study of atezolizumab and cobimetinib in PD-1/PD-L1 inhibitor resistant or refractory non-small cell lung cancer: ETCTN #10166.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9638-TPS9638
Author(s):  
Stephen V. Liu ◽  
Richard Delmar Hall ◽  
Andreas Nicholas Saltos ◽  
Gregory Alan Otterson ◽  
Ming Tony Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Resistance ◽  
Durable Response

TPS9638 Background: Use of checkpoint inhibitors, alone or with chemotherapy, has emerged as the preferred standard treatment for patients with advanced, driver-negative non-small cell lung cancer (NSCLC). While outcomes are superior to chemotherapy alone, only a subset of patients achieve durable response and long term survival. One potential mechanism of primary resistance to checkpoint inhibitors is the lack of tumor-infiltrating lymphocytes. Inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) increases the number of CD8+ T-cell within a tumor and has shown synergy with anti-programmed death-ligand 1 (PD-L1) antibodies. The combination of the MEK inhibitor cobimetinib and the PD-L1 antibody atezolizumab has led to limited responses in colorectal cancer, a tumor typically non-responsive to checkpoint inhibition. This phase II trial explores the combination of cobimetinib and atezolizumab in patients with PD(L)1-refractory NSCLC. Methods: This phase II study is being conducted through the Experimental Therapeutics Clinical Trials Network (ETCTN #10166). Eligible patients have advanced NSCLC with primary resistance to anti-PD(L)1 therapy (defined as progression noted within 6 months of initiating therapy) and tumor amenable to serial core biopsy. Patients will receive atezolizumab 840mg intravenously every 2 weeks and cobimetinib 60mg orally for 21 days in 28-day cycles. Two cohorts will enroll in parallel, defined by presence or absence of a KRAS mutation. Each cohort will employ a Simon two-stage design to test a null rate of 5% vs. 25% (power = 0.90, □ = 0.10). If > 1 of 9 patients in stage 1 achieve a partial response, an additional 15 patients are enrolled and if > 3 patients achieve a durable response, the combination will be worthy of further investigation. The primary endpoint is durable (> 6 months) response rate. Secondary endpoints are overall response rate, progression free survival, overall survival, duration of response and adverse events. Biopsies performed at baseline and after 3 weeks of therapy will assess the change in the density of tumoral CD8+ T-cells. Whole exome sequencing and immune cell profiling will also be performed on serial samples. Enrollment was initially limited to KRAS-mutant NSCLC. Prespecified activity goal for the first stage of accrual has been met; second stage accrual began in September 2019. Enrollment to the KRAS wild-type cohort will commence. Clinical trial information: NCT03600701 .

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