1235TiP Perioperative pembrolizumab + platinum-based chemotherapy for resectable locally advanced non-small cell lung cancer: The phase III KEYNOTE-671 study

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).

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Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.12.2354 ◽

2000 ◽

Vol 18 (12) ◽

pp. 2354-2362 ◽

Cited By ~ 977

Author(s):

Frank V. Fossella ◽

Russell DeVore ◽

Ronald N. Kerr ◽

Jeffrey Crawford ◽

Ronald R. Natale ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Phase Iii ◽

Control Treatment ◽

Rank Test ◽

Small Cell Lung ◽

Phase Iii Trial ◽

Platinum Based Chemotherapy

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m2 (D100) or 75 mg/m2 (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P = .001 and P = .036, respectively). Patients who received docetaxel had a longer time to progression (P = .046, by log-rank test) and a greater progression-free survival at 26 weeks (P = .005, by χ2 test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P = .025, by χ2 test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

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Using the Systemic Immune-Inflammation Index (SII) as a Mid-Treatment Marker for Survival among Patients with Stage-III Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17217995 ◽

2020 ◽

Vol 17 (21) ◽

pp. 7995

Author(s):

Tithi Biswas ◽

Kylie H. Kang ◽

Rohin Gawdi ◽

David Bajor ◽

Mitchell Machtay ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Locally Advanced ◽

Small Cell ◽

Phase Iii ◽

Stage Iii ◽

Small Cell Lung ◽

Cancer Data ◽

Immune Inflammation

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3–4) is a significant predictor of survival, and if the effect of PEM vs. ETO differs by quartile (Q) level of SII. Hazard-ratios (HR) for survival were estimated using a proportional hazards model, accounting for the underlying correlated structure of the data. A total of 548 patients were included in our analysis. The median age at baseline was 59 years. Patients were followed for a median of 24 months. Adjusting for age, body mass index, sex, race, and chemotherapy regimen, SII was a significant mid-treatment predictor of both overall (adjusted HR (aHR) = 1.6, p < 0.0001; OS) and progression-free (aHR = 1.3, p = 0.0072; PFS) survival. Among patients with mid-RT SII values above the median (6.8), those receiving PEM (vs. ETO) had superior OS (p = 0.0002) and PFS (p = 0.0002). Our secondary analysis suggests that SII is an informative mid-treatment marker of OS and PFS in locally advanced non-squamous NSCLC.

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