scholarly journals Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Butuo Li ◽  
Chao Jiang ◽  
Linlin Pang ◽  
Bing Zou ◽  
Mingjun Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Cell Death ◽  
Combination Treatment ◽  
Small Cell ◽  
High Grade ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Significant Difference

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.MethodsAn electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.ResultsEleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.ConclusionMost AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

scholarly journals MLTI-04. EVOLUTION OF TREATMENT PARADIGMS FOR PATIENTS WITH ≥1 BRAIN METASTASES FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i15-i15
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Nebras Warsi ◽  
Jetan Badhiwala ◽  
Alireza Mansouri
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Inhibitors ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Management Paradigms

Abstract BACKGROUND: Brain metastases (BM) are common in non-small cell lung cancer (NSCLC), with approximately 10% of patients presenting with BM at the time of diagnosis. The aim of this systematic review was to critically evaluate the evolution of management paradigms for BM from NSCLC. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, and CENTRAL for randomized controlled trials (RCTs) published until October 2018. Comparative RCTs based on ≥ 50 patients were selected. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 3188 abstracts, 14 RCTs (2494 patients) met inclusion criteria. Median sample size was 97 (range 59–538). Most trials were open-label, parallel, superiority trials. All included patients aged ≥18 with histologically proven NSCLC and ≥1 BM proven on CT/MRI. The majority of trials (11/14) excluded patients with non-favorable performance status (ECOG, KPS, or WHO scales), prior SRS or WBRT, and/or leptomeningeal metastases. Interventions assessed included WBRT (11/14), SRS (3/14), targeted therapies (e.g. EGFR inhibitors, 5/14), and various chemotherapeutic regimens (12/14). Most trials (12/13) reported no significant difference in OS between interventions. 4/10 trials reported a difference in PFS, two of which only included patients with EGFR-mutant NSCLC; these showed a significant increase in PFS in patients managed with EGFR inhibitors. The other two trials reported longer PFS with sodium glycididazole + WBRT vs. WBRT alone (p=0.038) and temozolomide + SRS vs. SRS alone (p=0.003). The incidence of adverse events was consistent across most treatment groups. CONCLUSIONS: Most trials showed no significant improvement in OS; however, improvement in PFS was seen in several trials, most notably in EGFR-positive patients treated with EGFR inhibitors. Given the long-standing merit of radiation-based therapies for BM management, these data support the need for an in-depth meta-analysis assessing the comparative efficacy of current management paradigms for specific patient populations.

Randomized Double-Blind Trial of Combined Modality Treatment With or Without Amifostine in Unresectable Stage III Non–Small-Cell Lung Cancer

2003 ◽  
Vol 21 (9) ◽  
pp. 1767-1774 ◽  
Author(s):  
Swan Swan Leong ◽  
Eng Huat Tan ◽  
Kam Weng Fong ◽  
Einar Wilder-Smith ◽  
Yew Kwang Ong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Combined Modality Treatment ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Significant Difference

Purpose: Greater toxicities have been recognized to be a consequence of combined chemotherapy and radiotherapy in the treatment of locally advanced non–small-cell lung cancer (NSCLC). This study was designed to determine if the use of amifostine could reduce treatment-related toxicities associated with the use of paclitaxel plus carboplatin and thoracic radiotherapy. Patients and Methods: Sixty patients with unresectable stage III NSCLC were treated with two cycles of paclitaxel 175 mg/m2 and carboplatin (area under the time-concentration curve = 6), followed by thoracic radiotherapy (64 Gy) with concurrent weekly paclitaxel 60 mg/m2. Patients were randomly assigned to receive 740 mg/m2 of amifostine (arm A) or placebo (arm B) before each dose of paclitaxel and carboplatin. Treatment-related toxicities were evaluated at each visit and nerve conduction tests were performed before and after treatment for the objective assessment of neurotoxicity. Results: There was no significant difference between arms A and B in grade 3 to 4 neutropenia. In all 72 neurophysiological parameters measured, there was no significant difference between the two treatment arms, although there was a trend toward fewer patients showing deterioration in arm A for six of the parameters. Grade 2 to 3 esophagitis occurred in 43% of patients in arm A and in 70% of patients in arm B. The difference of −27% (95% confidence limit = −50%, 0.4%) was not statistically significant. Response rates and survival were also not significantly different between the two arms. Conclusion: Pretreatment with amifostine showed a trend toward reducing the severity of esophagitis associated with concurrent chemoradiotherapy, but it did not reach statistical significance. There was no significant protective effect on hematologic or neurologic toxicities induced by paclitaxel and carboplatin.

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