scholarly journals Risk of SARS-CoV2-related Mortality in Non-small Cell Lung Cancer Patients Treated With First-line Immunotherapy Alone or in Combination With Chemotherapy

2021 ◽  
Author(s):  
Giuseppe Luigi Banna ◽  
Ornella Cantale ◽  
Alex Friedlaender ◽  
Harliana Yusof ◽  
Alfredo Addeo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
First Line ◽  
Risk Of Death ◽  
The Impact ◽  
Related Mortality

Abstract Background: Patients with cancer are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the impact of solid cancer types and systemic anticancer treatments on its related mortality is still debatable.Methods: To weigh the real impact of immune-checkpoint inhibitors (ICIs) by exploring the risk of SARS-CoV-2-related mortality in a retrospective analysis of patients with non-small-cell lung cancer (NSCLC) treated with first-line Pembrolizumab or in combination with chemotherapy (ChT) during the first surge of the pandemic. Results: The risk of death was significantly higher in the group of patients treated with ChT+Pembrolizumab than with Pembrolizumab alone (OR 2.43 (1.23-4.82, p=0.01). The SARS-CoV-2-related mortality rate was 8% and significantly associated with ChT+Pembrolizumab as compared to Pembrolizumab alone (18% vs. 0%, respectively, p=0.03). Patients dead because of SARS-CoV-2 were older than 70 years (100 vs. 34%, respectively, p=0.03) and tended to have a heavier smoking history (67 vs. 29% of current smokers, respectively, p=0.17). Higher baseline values of neutrophil-to-lymphocyte ratio (NLR) (with 67 vs. 50% ≥ 4.0, p=0.58) and systemic immune-inflammation index (SII) (with 67 vs. 50% ≥ 1236, p=0.58) were observed in patients dead due to the SARS-CoV-2.Conclusions: Immunotherapy might not impact the risk of SARS-CoV-2-related mortality, whilst the addition of ChT was either associated with an overall increased risk of mortality and to the risk of SARS-CoV-2-related mortality. The co-existence of other clinical factors may have contributed to the latter.

scholarly journals Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

2021 ◽  
Vol 9 (4) ◽  
pp. e002421
Author(s):  
Alessio Cortellini ◽  
Massimo Di Maio ◽  
Olga Nigro ◽  
Alessandro Leonetti ◽  
Diego L Cortinovis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc ◽  
The Impact

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

Successful treatment of pulmonary lymphangitic carcinomatosis by anlotinib in 14 Chinese patients with advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21064-e21064
Author(s):  
Shencun Fang ◽  
Wanwan Cheng ◽  
Yingming Zhang ◽  
Haitao Zhang ◽  
Si Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lymphatic Metastasis ◽  
Small Cell ◽  
Smoking History ◽  
Wild Type ◽  
Small Cell Lung ◽  
The Impact ◽  
Lymphangitic Carcinomatosis

e21064 Background: Pulmonary lymphangitic carcinomatosis (PLC) occurs in 6%-8% of intrathoracic metastases among malignant tumor. The median survival was only 2.0 months from time of pulmonary symptoms to death in cases during 2000-2018, which is a poor prognosis. Effective interventions were needed besides standard chemotherapy and symptomatic support. Anlotinib showed a critical effect on lymphangiogenesis, and lymphatic metastasis in mouse models of lung adenocarcinoma, it might be a therapeutic option for tumor lymphatic metastasis. In this study, we retrospectively analyzed the efficacy and safety of anlotinib for PLC in patients with Non-small Cell Lung Cancer (NSCLC). Methods: We retrospectively investigated NSCLC patients with PLC at our hospital between May 2018 and November 2020, who received anlotinib monotherapy or combined therapy for PLC. Data were analyzed for progression-free survival (PFS), overall survival (OS), objective response rate(ORR), disease control rate(DCR) and adverse events (AE). The impact of clinical and genomic factors on PFS and OS were also assessed. Results: A total of 14 patients were enrolled with a median age of 64 years. 10(71.4%) were male, 4(28.6%) has smoking history, 10(71.4%) of patients had a performance status of 2-3. 9, 3, 2 patients had TP53 mutation, EGFR mutation, ALK fusion respectively. 9(64.3%) patients received anlotinib monotherapy. Of 14 patients, 8 achieved partial response (PR), 5 presented stable disease (SD), 1 had progressed disease. The ORR and DCR were 57.1% and 92.9% respectively. The median PFS was 3.1 months (95% CI: 2.0-4.2), the median OS for 1, 2, ≥3 line were 13 months, 7.2 months, 5.2 months, respectively. Median PFS and OS (≥3 line) were significantly longer for patients with TP53-mutant tumors compared with those with TP53–wild-type tumors (median PFS: 7 vs. 1.1 months, median OS (≥3 line): 6.8 vs. 1.9 months). No difference of PFS and OS (≥3 line) was found between EGFR or ALK alteration and the corresponding wild type patients. The most frequently reported AEs were high blood pressure (11, 78.6%), hand foot syndrome (6, 42.9%), diarrhea (5, 35.7%), fatigue (4, 28.6%), hoarseness (3, 21.4%), proteinuria (2, 14.3%) and stomatitis (2, 14.3%). Conclusions: Anlotinib presented favorable efficacy in patients with pulmonary lymphangitic carcinomatosis and conferred considerable survival benefit compared with previous studies, especially in patients harboring TP53 mutations. The AEs were manageable. These indicated that anlotinib can be a promising therapeutic treatment of PLC. More clinical data is needed to validate this finding.

scholarly journals Body composition and inflammation impact in non-small cell lung cancer patients treated by first-line immunotherapy

Immunotherapy ◽  
2021 ◽  
Author(s):  
Cinzia Baldessari ◽  
Annarita Pecchi ◽  
Raffaella Marcheselli ◽  
Giorgia Guaitoli ◽  
Riccardo Bonacini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Body Composition ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
First Line ◽  
Risk Of Death ◽  
Inflammatory Status

Background: Immunotherapy changed the landscape of non-small cell lung cancer (NSCLC). Efforts were made to implement its action. This study aims to describe body composition, nutritional and inflammatory status in NSCLC patients treated by first-line immunotherapy, their correlation, variation and impact. Patients and methods: We retrospectively analyzed 44 consecutive patients who received pembrolizumab treatment. Results: During the therapy, inflammation and visceral fat increased, whereas muscle and subcutaneous fat decreased. Parameters related to inflammation had an interesting prognostic impact. High numbers of white blood cells remained significantly correlated with a high risk of death in multivariate model. Conclusion: For the best treatment choice, a combination of clinical and biological factors will be most likely be necessary. Prospective and larger studies with a multidimensional approach are needed.

Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy

Oncology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Hisao Imai ◽  
Takayuki Kishikawa ◽  
Hiroyuki Minemura ◽  
Yutaka Yamada ◽  
Tatsuya Ibe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Strongly Correlated ◽  
Small Cell Lung ◽  
First Line ◽  
Patient Level ◽  
The Impact

<b><i>Background:</i></b> Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. <b><i>Methods:</i></b> We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. <b><i>Results:</i></b> Linear regression analyses and Spearman’s rank correlation coefficient revealed that PPS was strongly correlated with OS (<i>r</i> = 0.76, <i>p</i> &#x3c; 0.05, <i>R</i><sup>2</sup> = 0.65), while PFS was only moderately correlated with OS (<i>r</i> = 0.71, <i>p</i> &#x3c; 0.05, and <i>R</i><sup>2</sup> = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both <i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.

scholarly journals Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 728-736
Author(s):  
Geng-wei Huo ◽  
Ran Zuo ◽  
Ying Song ◽  
Wei-dong Chen ◽  
Wen-ming Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Antibiotic Use ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
The Impact

Abstract This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30–90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13–3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81–4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5–1.7) and 8.8 months (95% CI: 8.5–9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

scholarly journals Impact of KRAS and TP53 Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With STK11-Mutated Advanced Non–Small-Cell Lung Cancer

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Erin Bange ◽  
Melina E. Marmarelis ◽  
Wei-Ting Hwang ◽  
Yu-Xiao Yang ◽  
Jeffrey C. Thompson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Systemic Therapy ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Stk11 Gene ◽  
The Impact

PURPOSE The STK11 gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non–small-cell lung cancer (NSCLC) and STK11 mutations often have other co-mutations. We evaluated the impact of KRAS and TP53 co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors STK11 mutations. METHODS We conducted a retrospective review of patients with metastatic NSCLC and STK11 mutations treated at the University of Pennsylvania. STK11 mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between STK11 co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). RESULTS From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an STK11 mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an STK11 mutation alone, 19 had STK11/ KRAS, 18 had STK11/ TP53, and seven had STK11/ KRAS/ TP53. Patients with STK11/ KRAS co-mutations had a worse median PFS (2.4 months) compared with STK11 alone (5.1 months; log-rank P = .048), STK11/ TP53 (4.3 months; log-rank P = .043), and STK11/ KRAS/ TP53 (13 months; log-rank P = .03). Patients with STK11/ KRAS co-mutation experienced shorter median OS (7.1 months) compared with STK11 alone (16.1 months; log-rank P < .001), STK11/ TP53 (28.3 months; log-rank P < .001), and STK11/ KRAS/ TP53 (22 months; log-rank P = .025). CONCLUSION Among patients with advanced NSCLC and STK11 mutations treated with first-line systemic therapy, co-mutation with KRAS was associated with significantly worse PFS and OS. By contrast, co-mutation of STK11 with TP53 conferred a better prognosis.

Evaluation of the incidence of pneumonitis in United States veterans with non-small cell lung cancer receiving durvalumab following chemoradiation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9034-9034
Author(s):  
Theodore Seth Thomas ◽  
Suhong Luo ◽  
Eric Marshall Knoche ◽  
Kristen Marie Sanfilippo ◽  
Jesse W. Keller
Keyword(s):  
Lung Cancer ◽  
Radiation Dose ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Disease Stage ◽  
Smoking History ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
Grade 3

9034 Background: Locally advanced, unresectable non-small cell lung cancer is commonly treated with concurrent chemoradiation therapy (CRT). Durvalumab is a PD-L1 immune checkpoint inhibitor (ICI) administered following completion of CRT. Pneumonitis is a known toxicity of ICI therapy. In the landmark PACIFIC study the incidence of pneumonitis in patients receiving durvalumab was 33.9% (any grade) and 3.4% (grade 3/4) compared to placebo 24.8% and 2.6% ( Antonia et al, NEJM 2017). The incidence of pneumonitis is thought to be higher in real-world populations. This study evaluated the incidence of pneumonitis in a cohort of U.S. Veterans. Methods: Durvalumab recipients were identified using VA Informatics and Computing Infrastructure databases. Using pharmacy records we confirmed durvalumab and corticosteroid prescriptions. Clinical information was obtained via the electronic medical record. The primary outcome was the development of pneumonitis. We defined asymptomatic pneumonitis as the presence of new radiographic findings consistent with pneumonitis without documented clinical symptoms. We recorded pneumonitis grade as reflected in clinical documentation. If not specifically graded, we used Common Terminology Criteria for Adverse Events (CTCAE v4.0) to assess severity. Logistic regression analysis evaluated associations between pneumonitis and age, comorbidities, radiation dose and stage. Cox proportional hazards analysis evaluated associations between pneumonitis and risk of death. Results: A total of 123 veterans received durvalumab through 3/31/2019 (with follow up through 11/15/2019). Asymptomatic radiographic infiltrates occurred in 49 (39.8%) patients. There were 26 cases of clinically important pneumonitis Grade 2: 9(7.3%), Grade 3: 14 (11.4%), Grade 4: 2(1.6%), and grade 5: 1 (.08%). Acute hypersensitivity reactions occurred in five (4.1%) patients. Reported reasons for discontinuation of durvalumab included: disease progression [38 (31%)], toxicity [30 (24.3%)], and patient death [1 (1.6%)]. There was no association between age, time from radiation end to durvalumab initiation, radiation dose, smoking history, chemotherapy used or disease stage on development of pneumonitis. Cox analysis did not demonstrate an association between pneumonitis and risk of death. Conclusions: Clinically significant pneumonitis was more frequent in this cohort than reported in prior clinic trial populations. Further studies to identify pneumonitis risk factors are needed.

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