scholarly journals Immune Checkpoint Blockade for Advanced NSCLC: A New Landscape for Elderly Patients

2019 ◽  
Vol 20 (9) ◽  
pp. 2258 ◽  
Author(s):  
Fabio Perrotta ◽  
Danilo Rocco ◽  
Fabiana Vitiello ◽  
Raffaele De Palma ◽  
Germano Guerra ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Elderly Patients ◽  
Advanced Nsclc ◽  
Cell Activity ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Efficacy And Safety ◽  
Older Subjects ◽  
Nsclc Patients ◽  
Careful Assessment

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.

Impact of rapid multigene assays with short turnaround time (TAT) on the development of precision medicine for non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9094-9094
Author(s):  
Shingo Matsumoto ◽  
Takaya Ikeda ◽  
Kiyotaka Yoh ◽  
Akira Sugimoto ◽  
Terufumi Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Targeted Therapies ◽  
Advanced Nsclc ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Gene Testing ◽  
Genomic Screening ◽  
Nsclc Patients

9094 Background: A variety of oncogene drivers have been identified in NSCLC and molecularly-stratified precision medicine has led to improved survival in advanced NSCLC. Next-generation sequencing (NGS)-based testing is utilized to detect actionable gene alterations; however, the TAT of NGS is often too long to translate into clinical decision making. Thus, rapid multi-gene testing alternatives are needed. Methods: A lung cancer genomic screening project (LC-SCRUM-Asia) capturing clinical outcome was established in 2013 to identify patients with oncogene drivers and to support the development of novel targeted therapies. Since February 2013 to May 2019 (LC-SCRUM-Asia 1st-phase), single gene testing and/or a targeted NGS assay, Oncomine Comprehensive Assay (OCA), were used for the genomic screening. Since June 2019 to December 2020 (2nd-phase), a multi-gene PCR assay (Amoy 9-in-1 test) and a rapid NGS assay (Genexus/Oncomine Precision Assay [OPA]) were also implemented as rapid multi-gene testing. Results: A total of 10667 Japanese NSCLC patients, including 6826 in the 1st-phase and 3841 in the 2nd-phase, were enrolled in the LC-SCRUM-Asia. Success rate for OCA: 93%, for 9-in-1 test: 98%, for Genexus/OPA: 96%. Median TAT for OCA: 21 days, for 9-in-1 test: 3 days, for Genexus/OPA: 4 days. The frequencies of genetic alterations detected in the 1st-/2nd-phase were EGFR: 17/24%, KRAS: 15/16%, HER2 ex20ins: 4/3%, ALK fusions: 3/3%, RET fusions: 3/2%, ROS1 fusions: 3/2%, MET ex14skip: 2/2%, BRAF V600E: 1/1%, NRG1 fusions: 0/0.2% and NTRK3 fusions: 0.05/0.04%. Overall percent agreement of 9-in-1 test compared with OCA for EGFR/KRAS/HER2/BRAF/MET/ALK/ROS1/RET/NTRK3 alterations was 98%, and that of OPA compared with OCA was 95%. The rate of patients who received targeted therapies as 1st-line treatment was significantly elevated in the 2nd-phase compared with the 1st-phase (510/3841 [13%] vs. 567/6826 [8%], p < 0.001). Through the genomic screening, 1410 (37%) and 1269 (18%) candidate patients for clinical trials of KRAS, HER2, BRAF, MET, ALK, ROS1, RET or TRK-targeted drugs were identified in the 2nd-phase and in the 1st-phase, respectively. The rate of patients who were actually enrolled into the genotype-matched clinical trials were also significantly higher in the 2nd-phase than in the 1st-phase (222 [6%] vs. 186 [3%], p < 0.001). In 1st-line treatments for advanced NSCLC patients, the median progression-free survival was 8.5 months (95% CI, 7.7−9.4) in the 2nd-phase (n = 1839) versus 6.1 months (95% CI, 5.9−6.3) in the 1st-phase (n = 4262) (p < 0.001). Conclusions: Both the 9-in-1 test and Genexus/OPA had short TATs (3−4 days), high success rates (96−98%) and good concordance (95−98%) compared with another NGS assay (OCA). These rapid multi-gene assays highly contributed to enabling precision medicine and the development of targeted therapies for advanced NSCLC.

scholarly journals Circulating Tumor Cell PD-L1 Expression as Biomarker for Therapeutic Efficacy of Immune Checkpoint Inhibition in NSCLC

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 809 ◽  
Author(s):  
Kloten ◽  
Lampignano ◽  
Krahn ◽  
Schlange
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Tissue Samples ◽  
Programmed Death ◽  
Nsclc Patients

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.

Efficacy and Safety of CHOP-14 in Elderly Patients with Very Poor Risk Diffuse Large B-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3307-3307
Author(s):  
Dorte Tholstrup ◽  
Peter de Nully Brown ◽  
Mads Hansen ◽  
Jesper Jurlander
Keyword(s):  
Clinical Trials ◽  
Cardiac Arrest ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Pneumocystis Carinii ◽  
B Cell Lymphoma ◽  
Efficacy And Safety ◽  
Poor Risk ◽  
Risk Patients

Abstract The outcome of advanced diffuse large cell B-cell lymphoma (DLBCL) has been improved by the “dose-densified” biweekly CHOP-14 regimen. The German NHL-B2 trial has demonstrated favourable efficacy and safety in elderly patients with performance status ≤ 3 and normal organ function. However, a considerable proportion of patients are not eligible for clinical trials due to high age, poor performance, concomitant disease and/or organ dysfunction. The efficacy and safety of CHOP-14 is unknown in this group of very poor risk patients. CHOP-14 was introduced as standard treatment for advanced DLBCL (CSII-IV and/or LDH above UNV and/or bulky tumor ≥ 7.5 cm) at our institution in 2002. Seventy consecutive patients with DLBCL have been treated with 6-8 series CHOP-14 in the period March 2002 to December 2003. Patients with residual disease following chemotherapy were subsequently treated with involved field radiation. In order to estimate the efficacy and safety of CHOP-14 in very poor risk patients, we divided this population into two cohorts; A: standard risk: pts. aged 60–75 years with PS ≤ 3 or pts. aged < 60 years regardless of PS and B: very poor risk: pts. aged 60–75 years with PS = 4 or pts. aged > 75 years regardless of PS. Patient characteristics Age PS ≥ LDH UNV Bulky CS III/IV Extranodal IPI 4–5 B-symptoms; A: 22/44 (50%), B: 15/26 (58%) A (n=44) 60 (26–73) 0 (0–4) 26 (59%) 19 (43%) 25 (57%) 24 (55%) 2 (5%) B (n=26) 76 (64–83) 2 (0–4) 22 (85%) 14 (54%) 21 (81%) 19 (73%) 17 (65%) The response rates in the two cohorts (A vs. B) were CR/Cru: 82% vs. 62% (p=0.06); PR: 2% vs. 8% (p=0.55); NC/PD: 11% vs. 8% (ns). Two year EFS was 66% vs. 37% (p=0.027) and the two year OS was 71% vs. 57% (p=0.04). Concerning toxicity 30/44 (68%) vs. 23/26 (88%) (p=0.08) required hospitalisation for one or more of the following reasons: 50% vs. 65% (p=0.21) due to infection; 9% vs. 15% (p=0.42) due to Pneumocystis Carinii pneumonia; 27% vs. 31% (p=0.75) due to reduced PS mainly caused by malnutrition. The median total number of days in hospital were 8 (1–162) vs. 39 (1–228) days (p=0.002). The therapy-associated deaths without progression were 2/44 (5%) in cohort A (1 cardiac arrest, 1 ileus) compared to 3/26 (12%) in cohort B (1 cardiac arrest, 1 PCP, 1 unknown) (ns). In 3 additional patients in cohort B, treatment was stopped early due to severe infection, resulting in progression and subsequently death. In general dose erosion was minimal, except for vincristin that was reduced due to neuropathy in 20/44 (45%) vs. 10/26 (38%) (p=0.57) of the patients after a median of 5 vs. 4 cycles. The median delay in treatment schedule (schedule erosion) was 8 days (0–95 days) vs. 14 days (0–67 days) (p=0.06). Given the dismal prognosis of the patients in cohort B, the two-year survival rate of 57% is encouraging. However, the increased toxicity with infections and malnutrition, warrants for careful attention to this high risk group of patients, preferably within clinical trials focused on prevention and treatment of infections, improvement of the nutritional status and quality of life.

scholarly journals Overview of Current Progress in Immune Checkpoint Inhibitor Therapy for Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382094748
Author(s):  
Xinlun Dai ◽  
Shupeng Wang ◽  
Chunyuan Niu ◽  
Bai Ji ◽  
Yahui Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Inhibitory Signaling

Hepatocellular carcinoma (HCC) remains to a common cause of tumor mortality worldwide and represents the most common type of lethal hepatic malignancy. The incidence of HCC is swiftly increasing in western countries and southeast Asia. Despite poor prognosis, traditional treatments for advanced HCC appear to be minimally effective or even useless since patients are usually diagnosed in the advanced stage of disease. In recent years, immune checkpoint blockade has shown promising results in multiple pre-clinical and clinical trials of different solid tumors, including advanced HCC. Novel drugs targeting immune checkpoints, such as nivolumab (anti-PD-1), durvalumab (anti-PD-L1), and tremelimumab (anti-CTLA-4) have been shown to be highly effective and relatively safe in monotherapy or in combination treatment of advanced liver cancer. Unlike other immunotherapies, this approach can rouse human anti-tumor immunity by relieving T-cell exhaustion and inhibiting the evasion of HCC by blocking co-inhibitory signaling transduction accurately. In this review, we will provide current knowledge of several major immune checkpoints and summarize recent data from clinical trials that applied immune checkpoint inhibitors alone or in combination. In addition, this review will discuss the limitations and future prospective of immune checkpoint-targeted therapy for advanced HCC.

First-line gefitinib for elderly patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations: A combined analysis of NEJ studies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7563-7563
Author(s):  
Sodai Narumi ◽  
Akira Inoue ◽  
Naoto Morikawa ◽  
Yuji Minegishi ◽  
Makoto Maemondo ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Reference Group ◽  
Safety Data ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
First Line ◽  
Younger Patients ◽  
Egfr Mutated

7563 Background: The first-line treatment with gefitinib has been established as a standard of care for advanced NSCLC patients with EGFR mutation by previous studies including NEJ002. Since the percentage of elderly population in those studies was lower than that of real situation, further validation of its usefulness for elderly patients with EGFR-mutated NSCLC is warranted. Methods: The efficacy and safety data of fit elderly patients (70 years or older with PS 0-2) with EGFR-mutated NSCLC who received the first-line gefitinib in NEJ001 (phase 2), NEJ002 (phase 3), and NEJ003 (phase 2) were combined. Same population treated with the first-line carboplatin plus paclitaxel in NEJ002 (n=34) were also examined their efficacy and safety for reference. Regarding the toxicity and quality of life (QOL), the comparison between elderly patients and younger patients (< 70 years old) both treated with first-line gefitinib in NEJ002 was also performed. Results: Data from 71 patients (7 from NEJ001, 33 from NEJ002, 31 from NEJ003) treated with first-line gefitinib were combined. Patients’ characteristics were as follows; mean age: 76.8 years (range 70-89), female: 73%, never smoker: 75%, PS 0-1: 92%. Overall response rate (73.2%) and median progression-free survival (14.3 months) in this group were significantly better than those in the reference group (26.5% and 5.7 months, respectively). Despite fewer patients received second-line chemotherapy in the first-line gefitinib group, its median overall survival (30.8 months) was not inferior to that of reference group (26.4 months). Regarding toxicities such as liver dysfunction, rash, diarrhea, and pneumonitis, and QOL examined by self questionnaires, there were no difference between the elderly patients and younger patients in NEJ002. Conclusions: First-line gefitinib still achieved high efficacy with acceptable toxicity in fit elderly patients with advanced NSCLC harboring EGFR mutation. Considering that elderly patients tend to receive fewer treatment lines compared with younger patients, first-line gefitinib would be strongly recommended for this population to avoid the risk of missing its administration.

The efficacy and safety of EGFR-TKI combined with chemotherapy in NSCLC patients with EGFR co-mutation with other oncogenic alterations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21077-e21077
Author(s):  
Wenhua Zhao ◽  
Wei Jiang ◽  
Hongtu Qiu ◽  
Aiping Zeng ◽  
Xiangqun Song ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Monotherapy Group ◽  
Efficacy And Safety ◽  
Observation Study ◽  
Primary Resistance ◽  
Nsclc Patients ◽  
Egfr Tki

e21077 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations. However, the optimal therapeutic regimen for advanced NSCLC with EGFR co-mutation was still unknown. This respective observation study aimed to assess the efficacy and safety of the combination therapy with EGFR-TKI and chemotherapy in this sub-population. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR mutation detected using next-generation sequencing targeting 59 genes were screened for eligibility. We included patients of EGFR co-mutation with other oncogenic alterations receiving EGFR-TKI monotherapy or TKI plus chemotherapy as first-line therapy. The primary outcome was objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 48 patients were enrolled. Among patients with concomitant mutation, the combination of chemotherapy with TKI was found to prolong mPFS (12.5 vs 7.3 months; HR, 0.38; 95%CI: 0.17-0.81; P = 0.012) compared with TKI monotherapy, with a trend of longer mOS (27.0 vs 22.4 months; HR, 0.40; 95%CI: 0.15-1.05; P = 0.062) and higher ORR (68.4% vs 44.8%, P = 0.113). The DCR were 100% in combination group and 93.1% in monotherapy group (P = 0.99). A proportion of 13.8% patients reported grade≥3 treatment-related adverse events in monotherapy group and 36.8% in combination group. Conclusions: EGFR co-mutation with other oncogenic alterations associated with poor treatment outcome with EGFR-TKI monotherapy. The combination of EGFR-TKI and chemotherapy was effective in this sub-population and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.

scholarly journals Efficacy and Safety of Weekly Low Dose Paclitaxel and Cisplatin as First Line Therapy in Advanced NSCLC of Elderly Patients

2007 ◽  
Vol 6 (2) ◽  
pp. 85
Author(s):  
Jung Ho Lee ◽  
Mi Hye Kwon ◽  
Ji Hyun Jeoung ◽  
Go Eun Lee ◽  
Eu Gene Choi ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Low Dose ◽  
Advanced Nsclc ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Phase II randomized trial of erlotinib versus vinorelbine in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) aged ≥70 years in Taiwan

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8051-8051
Author(s):  
Y. Chen ◽  
C. Tsai ◽  
J. Shih ◽  
R. Perng ◽  
J. Whang-Peng
Keyword(s):  
Elderly Patients ◽  
Disease Control ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Disease Control Rate ◽  
Efficacy And Safety ◽  
Oral Vinorelbine ◽  
The Difference

8051 Background: Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors, such as erlotinib, are effective against NSCLC, especially in East Asian patients. Single-agent chemotherapy, such as vinorelbine, is an appropriate treatment choice for elderly patients. Oral vinorelbine is more convenient for elderly patients than intravenous vinorelbine. The primary objective of this study was to compare the response rate of chemo-naïve, elderly patients with advanced NSCLC treated with daily erlotinib versus oral vinorelbine. Methods: Chemo-naïve Taiwanese patients aged ≥70 years with advanced NSCLC were enrolled and randomized (stratified by histology, smoking status, ECOG performance status, and gender) to receive either oral erlotinib 150mg/day or oral vinorelbine (60mg/m2 on days 1 and 8 of the first cycle and subsequently increased to 80mg/m2 every 3 weeks in the absence of grade 2 adverse events). From February 2007 to July 2008, 116 patients were enrolled. Results: By October 2008, 77 enrolled patients (n = 37 for erlotinib; n = 40 for vinorelbine) had completed 6 cycles of study treatment and were available for efficacy and safety analyses. Objective response rates were 21.6% (8/37) with erlotinib and 12.8% (5/39) with vinorelbine [95% CI -0.09–0.24 for the difference in response rate between arms]. Disease control rate was 70.3% with erlotinib and 56.4% with vinorelbine [95% CI -0.09–0.34 for the difference in disease control rate between arms; p = 0.216). Median time to disease progression was 4.4 months [95% CI 4.1–5.4] with erlotinib, compared with 3.9 months [95% CI 2.4–6.9] with vinorelbine, p = 0.6069. The most common treatment-related toxicities were skin rash and diarrhea with erlotinib, and diarrhea and nausea with vinorelbine. Conclusions: Erlotinib is effective and well tolerated compared with oral vinorelbine in elderly, chemo-naïve, Taiwanese patients with NSCLC. Updated efficacy and safety data will be presented. [Table: see text]

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