Association between immune-related adverse events (irAEs) and atezolizumab efficacy in advanced NSCLC: analyses from the Ph III study OAK

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S56-S56
Author(s):  
N Reinmuth ◽  
K Syrigos ◽  
J Mazieres ◽  
D Cortinovis ◽  
R Dziadziuszko ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc

440 Activity and safety of camrelizumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced non-small-cell lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A466-A466
Author(s):  
Guo Gui Sun ◽  
Jing Hao Jia ◽  
Peng Gao ◽  
Xue Min Yao ◽  
Ming Da Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Large Sample Size ◽  
Small Cell Lung ◽  
Previously Treated ◽  
Line Chemotherapy

BackgroundEffective options are limited for patients with non–small-cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy. Camrelizumab is a potent anti-PD-1 monoclonal antibody and has shown promising activity in NSCLC. We assessed the activity and safety of camrelizumab for patients with previously treated, advanced NSCLC patients with negative oncogenic drivers.MethodsPatients who progressed during or following platinum-based doublet chemotherapy were enrolled. All patients received camrelizumab(200 mg)every 3 weeks or in combination with chemotherapy until loss of clinical benefit. The primary endpoint was objective response rate (ORR), other endpoints included disease control rate (DCR), progression-free survival (PFS) and safety.ResultsBetween Aug 5, 2019, and Jun 19, 2020, we enrolled 29 patients, 25 patients were available evaluated, ORR and DCR was 36% (9/25) and 92% (23/25), respectively. 25 of 29 patients were still receiving the treatment, the median PFS was not yet achieved. Compared with those without reactive cutaneous capillary endothelial proliferation (RCCEP), patients with RCCEP had higher ORR (60% vs. 28.6%). Treatment-related adverse events (AEs) occurred in 69.0% of patients (all Grade), and the most common were RCCEP (37.9%), pneumonitis (6.9%), and chest congestion (6.9%). Treatment-related grade 3 to 4 adverse events occurred in 10.3% of patients.ConclusionsIn patients with previously treated advanced NSCLC, camrelizumab demonstrated improved ORR and DCR, compared with historical data of the 2nd line chemotherapy, with a manageable safety profile. While patients with RCCEP derived greater benefit from camrelizumab. Further studies are needed in large sample size trials.

scholarly journals Association between immune-related adverse events (irAEs) and atezolizumab efficacy in advanced NSCLC: analyses from the phase III study OAK

2017 ◽  
Vol 28 ◽  
pp. v469 ◽  
Author(s):  
J. von Pawel ◽  
K. Syrigos ◽  
J. Mazieres ◽  
D. Cortinovis ◽  
R. Dziadziuszko ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Phase Iii ◽  
Phase Iii Study

The combination of EGFR-TKIs and anlotinib as a first-line therapy for EGFR-mutant advanced non-small cell lung cancer: A multicenter, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9030-9030
Author(s):  
Zhiyong He ◽  
Jinghui Lin ◽  
Yueming He ◽  
Jing Zhang ◽  
Dongyong Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Advanced Nsclc ◽  
De Novo ◽  
Egfr Mutations ◽  
Treatment Naïve ◽  
Pre Treatment ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

9030 Background: Currently,EGFR-TKIs are widely accepted as the standard treatment for EGFR- mutant advanced non-small-cell lung cancer (NSCLC); however, acquired resistance is inevitable. Combination therapy is considered as a strategy to overcome the resistance to EGFR-TKIs. Anlotinib, a novel multi-targeting, small-molecule TKI, has shown active to suppress tumor angiogenesis and growth. However, there is still a lack of evidence supporting the use of EGFR-TKIs in combination with anlotinib for the treatment of NSCLC until now. A multi-center, single-arm, phase II clinical trial was therefore designed to examine the efficacy and safety of EGFR-TKIs combined with anlotinib for treatment-naïve, advanced NSCLC patients, and unravel the possible mechanisms. Methods: This study was conducted in 14 research centers in Fujian, China. The main eligibility criteria were stage IV or relapsed nonsquamous NSCLC with EGFR mutations (exon 19 deletion,, and L858R), ECOG score 0-2,and age 20 to 75 years and no previous systemic treatment. Patients with asymptomatic brain metastases were admitted.Eligible patients were given gefitinib (250 mg QD) or icotinib (125 mg TID) in combination with anlotinib (10 mg per day, on days 1‒14; 21 days per cycle) until disease progression. The primary endpoint is progression-free survival (PFS) and safety, and the secondary endpoint is overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Peripheral blood was sampled pre-treatment, once every two months during treatment and after disease progression, and T790M mutation was detected in plasma ctDNA using a droplet digital PCR (ddPCR) assay. Results: Of 60 patients enrolled (August 2, 2018 to May 28, 2020). As of February 1, 2021, 37 patients (61.7%) experienced PFS events and 10 (16.7%) died. The ORR was 78.3%, and the DCR was100%.Median PFS was 13.0 months (95%CI,10.7-15.3).The 5 most common treatment-related adverse events included rash (63.3%), fatigue (55.0%), hypertension (48.3%), diarrhea (33.3%) and hand-foot syndrome (30.0%), and grade 3 adverse events included hypertension (5.0%), rash (1.67%), hypertriglyceridemia (1.67%), vomiting (1.67%) and elevated ALT (1.67%); no grade 4 adverse events or drug-related deaths were observed. Peripheral blood samples were collected from 36 patients pre-treatment, and 30.6% were identified with low-frequency de novo T790M mutations, with the mutation-allele frequency (MAF) ranging from 0.01% to 0.28%. Conclusions: The combination of the first-generation EGFR-TKIs and anlotinib shows impressive ORR and DCR, and acceptable toxicity in treatment-naïve advanced NSCLC patients with activating EGFR mutations, and we observed a high proportion of patients harboring de novo EGFR T790M mutations in this study. Clinical trial information: NCT03720873.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small cell lung cancer: A prospective and multicenter phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
Weize Lv ◽  
Beilong Zhong ◽  
Wenhua Zhao ◽  
Zhong Lin ◽  
Xiaofeng Pei ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Recombinant Human Endostatin ◽  
Phase 2 Trial

e21079 Background: Although the administration of immune checkpoint inhibitors (ICIs) and antiangiogenic agents in advanced non–small-cell lung cancer (NSCLC) has been well established, evidence supporting the combination of immune checkpoint inhibitors plus antiangiogenic drugs in previous treatment patients with advanced NSCLC is insufficient. We aimed to investigate the efficacy and safety of nivolumab combined with recombinant human endostatin (rh-Endostatin) as second-line or later treatment for advanced NSCLC. Methods: In this prospective and multicentre phase 2 trial we enrolled patients with advanced NSCLC who had not responded to standardized first-line treatment regimen from two cancer centres in China. Eligible patients were those aged 18-75 years without ICIs in first-line treatment who received nivolumab (3mg/kg, intravenous drip, day 1) every 2 weeks and rh-Endostatin (30 mg, 24-hour continous intravenous infusion，day 1–7) every 4 weeks till disease progression or discontinuation. The primary end points were objective response rate and safety. This study is registered with Chinese Clinical Trial Registry, number ChiCTR1900023664. Results: A total of 35 patients (median age, 60 years; range, 37-72 years) received nivolumab and rh-Endostatin. Median previous treated line of eligible patients was 2 lines (range, 1-7 lines). Patients received a median of 2 cycles of therapy (range, 1-14 cycles). Eleven of 33 evaluable patients achieved confirmed partial response with an objective response rate of 33.3% (11/33, 95% confidence interval [CI]: 17.2% – 49.4%) and disease control rate of 60.6% (20/33,95%CI:43.9%–77.3%). Median follow-up was 8.2 months (range: 0.9 –17.1). Median progression-free survival was 7.1 months (95% CI: 1.2m–13.0m), median overall survival was not reached and the 6-month overall survival rate was 54.5% (95% CI:37.6%–71.4%). The predominant grade 1-2 adverse events were thyroiditis, arrhythmia, hypertension. The grade 3 treatment-related adverse events were pneumonitis (3/35, 8.6%), hypertension (1/35, 2.9%) and atrial fibrillation (1/35, 2.9%), respectively. No grade 4 or 5 treatment-related adverse events were observed. Conclusions: To the best of our knowledge, this is the first prospective study that assessed nivolumab combined with rh-Endostatin as second-line or later treatment in pretreated patients with advanced NSCLC. In view of its encouraging efficacy and safety profile, nivolumab plus rh-Endostatin represents a promising treatment regimen in this patient population. Clinical trial information: ChiCTR1900023664.

scholarly journals P1.01-78 Treatment-Related Adverse Events in Patients with Advanced NSCLC Treated with First-Line Atezolizumab Chemoimmunotherapy

2019 ◽  
Vol 14 (10) ◽  
pp. S390
Author(s):  
S. Swarup ◽  
K. Thein ◽  
A. Sultan ◽  
N. Jahan ◽  
M. Quirch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
First Line

Immune-related adverse events in advanced NSCLC treated with immunotherapy alone or concurrent chemotherapy and immunotherapy.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 83-83
Author(s):  
John Melson ◽  
Daniel Reed ◽  
Bethany J. Horton ◽  
Margaret Moore ◽  
Jacqueline Theresa Brown ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Therapy Group ◽  
Stage Iv ◽  
Standard Of Care ◽  
Concurrent Chemotherapy ◽  
Increased Risk ◽  
Treatment Naïve

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]

A phase I clinical trial to assess the safety, pharmacokinetics, and antitumor activity of glumetinib (SCC244) in patients with advanced non-small cell lung cancers (NSCLCs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21702-e21702
Author(s):  
Hua-Jun Chen ◽  
Jin-Ji Yang ◽  
Xuening Yang ◽  
Qing Zhou ◽  
Minghui Sun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase I ◽  
Dose Escalation ◽  
Advanced Nsclc ◽  
Clinical Activity ◽  
Maximum Plasma ◽  
Open Label ◽  
Elevated Alkaline Phosphatase ◽  
Once Daily

e21702 Background: Aberrant activation of the MET pathway is associated poor prognosis and poor response to standard therapies in cancer patients. Glumetinib (SCC224) is an oral potent and highly selective MET inhibitor. This is an open label, dose-escalation, phase I clinical study to determine the safety, pharmacokinetics and anti-tumor activity in patients with advanced NSCLC regardless of MET status. Methods: Patients with advanced NSCLC failed standard treatments received glumetinib orally according to one of four dose escalation regimens on a 28-day cycle: 100 mg, 200 mg, 300mg and 400 mg once daily, in a Pharmacologically Guided Dose Escalation (PGDE) design (a variation of the standard 3+3 design). The primary endpoints are the incidence of dose limit toxicity (DLT), maximally tolerated dose (MTD), biologically effective dose (BED). The secondary endpoints are treatment-emergent adverse events (TEAE), safety and tolerability, anti-tumor efficacy, pharmacokinetics, and its metabolites. Results: As of Feb 7, 2020, a total of eighteen eligible (18) patients were enrolled into this study: 3 at 100 mg, 3 at 200 mg, 6 at 300 mg and 6 at 400 mg. Only one patient among 6 evaluable patients at 400mg cohort reported one DLT of grade 3 vomiting. Treatment-related adverse events mostly were grade 1 or 2 nausea, vomiting, elevated alkaline phosphatase, elevated conjugated bilirubin, edema, headache, asthenia and decreased appetite. Non-DLT treatment related G3/4 adverse events were peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%). Absorption was rapid after dosing and the median time to reach maximum plasma drug concentration ( Tmax) was 2.0‐6.0 hours. The mean value of half-life(t1/2) in each dose group ranged from 20.43h to 35.36 h. In response to glumetinib, one patient with MET overexpression at 200mg dose level had a best of response of partial response and completed 44 weeks glumetinib treatment, 4 patients (3 with MET amplification) had a best of response of stable disease. Conclusions: Glumetinib was well tolerated at doses up to 400 mg once daily and demonstrated clinical activity in advanced NSCLC with MET alterations. Glumetinib is used in ongoing clinical trials to further explore safety and efficacy in NSCLC. Clinical trial information: NCT03466268.

scholarly journals To Evaluate the Safety and Efficacy of Drug‐eluting Beads Bronchial Arterial Chemoembolization Loaded with Pirarubicin in the Treatment of Advanced Non-small-cell Lung Cancer

2021 ◽  
Author(s):  
Zhaonan Li ◽  
Quanjing Chen ◽  
Dechao Jiao ◽  
Xinwei Han
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Drug Eluting Beads ◽  
Drug Eluting ◽  
Grade 3 ◽  
Arterial Chemoembolization

Abstract Objectives The control of solid tumors by drug-eluting beads has been recognized in clinical practice, but there are still few applications regarding drug‐eluting beads bronchial arterial chemoembolization (DEB‐BACE) in lung cancer. To further investigate the role of DEB-BACE in patients with lung cancer. We evaluated the efficacy and safety of Pirarubicin-loaded CalliSpheres beads in patients treated for advanced non-small cell lung cancer (NSCLC). MethodsFrom June 2017 to January 2018, 54 patients with advanced NSCLC received DEB‐BACE with Pirarubicin‐loaded CalliSpheres® beads. After the treatment, the progression-free survival (PFS) and overall survival (OS) were analyzed. Moreover, adverse events and complications were also reported. ResultsAfter DEB‐BACE treatment, most of the adverse events and complications were CTCAE grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated) . Of the 54 patients, 2 persons (4%) had grade-3 lung abscess and required percutaneous drainage, 1(2%) had a grade-3 pulmonary infection that caused difficulty breathing and required intravenous antibiotics and ventilator adjuvant therapy. Moreover, the patient’s mean PFS was 7.828 months (95% CI: 6.614, 9.043), and the mean OS rates were 17.678 months (95% CI: 15.573, 19.783). Additionally, both univariate and multivariate cox regression indicated that the disease stage (stage III) seems related to better PFS in patients with advanced NSCLC (P=0.013). ConclusionsThe clinical effect of DEB‐BACE with Pirarubicin‐loaded CalliSpheres® beads on advanced NSCLC is probably significant and could improve the PFS, the adverse events and complications were tolerable.

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