132PD Plasma concentrations of pemetrexed to predict clinical outcomes in patients with advanced NSCLC

Abstract Abstract 4284 Introduction Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. Aims To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. Results In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. Conclusions IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed. Disclosures: No relevant conflicts of interest to declare.

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Long-term clinical outcomes of ALK inhibitors in patients with ALK-positive advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20542 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20542-e20542

Author(s):

Haruyasu Murakami ◽

Akira Ono ◽

Kazuhisa Nakashima ◽

Shota Omori ◽

Kazushige Wakuda ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Alk Inhibitors ◽

Alk Inhibitor ◽

Alk Positive

e20542 Background: Anaplastic lymphoma kinase (ALK) inhibitors show high clinical efficacy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the long-term clinical outcomes remain unknown. Methods: We retrospectively reviewed medical records of patients with ALK inhibitor-naïve ALK-positive advanced NSCLC who initiated alectinib or crizotinib therapy at the Shizuoka Cancer Center between June 2010 and December 2011. Results: This retrospective study included 14 patients (male/female, 5/9; PS 0/1, 6/8; adenocarcinoma/adenosquamous carcinoma, 13/1; smoker/never smoker, 8/6; brain metastasis presence/absence, 5/9; number of prior chemotherapy regimens 0/1/≥2, 1/7/6; alectinib/crizotinib, 4/10) with a median age of 55 years (range, 28-71). At the data cut-off (January 16, 2017), three patients were still receiving first ALK inhibitors (alectinib in two patients and crizotinib in one). One patient requested the discontinuation of alectinib therapy after five years. One patient discontinued crizotinib therapy due to unacceptable toxicity. Nine patients discontinued first ALK inhibitors due to disease progression. The overall response rate was 78.6% with complete response in two patients (14.3%), partial response in nine (64.3%), stable disease in one (7.1%), and progressive disease in two (14.3%). The median progression-free survival (PFS) for all 14 patients was 15.3 months, and the five-year PFS rate was 35.7%. The five-year PFS rates in patients treated with alectinib and crizotinib were 75.0% and 20.0%, respectively. The median overall survival (OS) for all 14 patients was 36.8 months, and the five-year OS rate was 42.9%. The five-year OS rates in patients treated with alectinib and crizotinib were 75.0% and 30.0%, respectively. Conclusions: ALK inhibitors showed favorable long-term clinical outcomes in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC, especially in patients treated with alectinib.

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Clinical outcomes of EGFR exon 20 insertion in advanced NSCLC in Korea.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e21136 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e21136-e21136

Author(s):

Seonggyu Byeon ◽

Youjin Kim ◽

Jiyun Lee ◽

Jong-Mu Sun ◽

Yoon-La Choi ◽

...

Keyword(s):

Clinical Outcomes ◽

Advanced Nsclc ◽

Exon 20

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Physiologic colonic uptake of 18F-FDG on PET/CT predicts immunotherapy response and gut microbiome diversity in patients with advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9600 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9600-9600

Author(s):

Lena Cvetkovic ◽

Claudine Régis ◽

Valerio Iebba ◽

Lisa Derosa ◽

Antoine Leblond ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Gut Microbiome ◽

Advanced Nsclc ◽

Surrogate Marker ◽

Small Cell ◽

High Uptake ◽

Small Cell Lung ◽

Pet Ct

9600 Background: Immune checkpoint inhibitors (ICI) represent the backbone treatment of advanced non-small cell lung cancer (aNSCLC) patients. Emerging evidence suggests increased gut microbiome (GM) diversity is associated with favorable response. Conversely, antibiotic-induced dysbiosis may be associated with deleterious outcomes in patients receiving ICI in multiple retrospective studies and one prospective study. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics and could be a surrogate marker for GM diversity and therefore clinical response. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with outcomes and GM metagenomics in patients with advanced NSCLC. Methods: 71 patients with aNSCLC who underwent PET/CT prior to ICI were identified. For each patient, the colon was manually contoured, SUVmax was measured in each segment of the colon by a nuclear medicine specialist and average SUVmax was calculated for the whole colon. Patients were stratified in two groups according to median colon SUVmax (low vs high uptake). 18F-FDG physiologic colonic uptake was then compared to overall survival (OS), objective response (ORR), and progression-free survival (PFS). For patients with available stool samples (n = 10), GM composition was defined using metagenomics sequencing. Results: 71 patients (54% men, median age: 68 years) with aNSCLC were included in the study and ICI was the first line of therapy in 38% of those patients. The mean colon SUV for the low and high uptake groups were 1.41 (CI 95% 1.35-1.47) and 2.18 (CI 95% 1.90-2.46) respectively. The high uptake group had a higher proportion of non-responders (p = 0.033) and significant shorter PFS (4.1 months vs 11.3 months, p = 0.005). In the caecum, high uptake also correlated with numerically shorter OS (10.82 vs 27.56 months, p = 0.058) compared to low uptake group. Despite the low number of samples, metagenomics sequencing revealed that PLS-DA (Partial Least Squares Discriminant Analysis) for diversity was lower in the high SUV group (p = 0.008). Conclusions: Higher colon SUVmax on pre-ICI FDG PET/CT is associated with worse clinical outcomes and lower baseline GM diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a surrogate marker of GM diversity and predicts clinical outcomes.

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P1.07-024 ISEND May Predict Clinical Outcomes for Advanced NSCLC Patients on PD-1/PD-L1 Inhibitors but Not Chemotherapies or Targeted Kinase Inhibitors

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.942 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2005

Author(s):

W. Park ◽

D. Kwon ◽

A. Desai ◽

V. Florou ◽

D. Saravia ◽

...

Keyword(s):

Clinical Outcomes ◽

Kinase Inhibitors ◽

Advanced Nsclc ◽

Nsclc Patients

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Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.630136 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kenji Morimoto ◽

Tadaaki Yamada ◽

Chieko Takumi ◽

Yuri Ogura ◽

Takayuki Takeda ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Confidence Interval ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Hazard Ratio ◽

Small Cell Lung

BackgroundThe immunotherapy plus chemotherapy combination is one of the most promising treatments in advanced non-small-cell lung cancer (NSCLC). Immunotherapy often causes immune-related adverse events (irAEs), which have been reported to be associated with the good clinical outcomes. However, the effects of immunotherapy plus chemotherapy remain unknown. In this study, we investigated the association between irAEs caused by immunotherapy plus chemotherapy and clinical efficacy in patients with advanced NSCLC.Materials and MethodsWe retrospectively analyzed the data of patients with advanced NSCLC, who received a combination of immunotherapy plus chemotherapy at six institutions in Japan between January 2019 and September 2019. We examined the effect of irAEs on various clinical outcomes.ResultsWe included 70 patients with advanced NSCLC. Patients were divided into two groups: patients with irAEs and patients without irAEs. Patients with irAEs had significantly longer progression-free survival than those without irAEs on univariate (hazard ratio 0.53, 95% confidence interval 0.30–0.93, p = 0.026) and multivariate (hazard ratio 0.53, 95% confidence interval 0.29–0.97, p = 0.041) analyses. In addition, patients with grade 1–2 irAEs (mild irAEs) had significantly longer progression-free and overall survival than those with grade 3-5 irAEs (severe irAEs) or without irAEs on univariate (398 days versus 189 days, respectively; p = 0.0061) and multivariate (not reached versus 412 days, respectively; p = 0.021) analyses.ConclusionPatients with NSCLC who experienced mild irAEs showed better response to treatment with immunotherapy plus chemotherapy than those with severe irAEs or without irAEs. Further large-scale research is warranted to confirm these findings.

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Clinical outcomes in patients with advanced NSCLC treated with targeted therapies, with actionable mutations identified by InVisionFirst ctDNA assay

Annals of Oncology ◽

10.1093/annonc/mdy318.006 ◽

2018 ◽

Vol 29 ◽

pp. vi8-vi9

Author(s):

J. Remon ◽

L. Mezquita ◽

S. Ortiz-Cuaran ◽

C. Jovelet ◽

L. Lacroix ◽

...

Keyword(s):

Clinical Outcomes ◽

Targeted Therapies ◽

Advanced Nsclc

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Preliminary safety and effectiveness of bevacizumab (BV) based treatment in subpopulations of patients (pts) with non-small cell lung cancer (NSCLC) from the ARIES study: A bevacizumab (BV) treatment observational cohort study (OCS)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8040 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8040-8040 ◽

Cited By ~ 2

Author(s):

N. A. Fischbach ◽

D. Spigel ◽

J. Brahmer ◽

J. Garst ◽

R. Robles ◽

...

Keyword(s):

Clinical Outcomes ◽

Advanced Nsclc ◽

The Elderly ◽

Phase Iii ◽

Cohort Size ◽

Treatment Benefit ◽

Phase Iii Trials ◽

Observational Cohort ◽

Ecog Ps ◽

Total Accrual

8040 Background: Phase III trials have shown that bevacizumab (Avastin, BV), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. To further define clinical outcomes associated with BV treatment among a broader population of NSCLC pts in a real-world setting, the ARIES OCS was initiated. Pt populations in OCSs are often more reflective of pts encountered in practice, permitting examination of treatment benefit and toxicity in subgroups that might be too small for study in traditional randomized controlled trials (RCTs). The NSCLC cohort in ARIES will assess clinical outcomes in the overall cohort as well as subpopulations such as the elderly, pts with poor PS or pts on concurrent anticoagulants (AC). Methods: Pts with advanced NSCLC whose 1st-line therapy includes BV may enroll. 257 sites are enrolling pts; total accrual of 2000 pts is expected. There are no protocol-specified treatments or assessments. Data is collected at baseline (BL) then quarterly, including targeted adverse events (AEs) and BV-related serious AEs. Clinical outcomes will be descriptively summarized by baseline characteristics. Multivariate analyses will be conducted if cohort size is sufficient. Results: As of 9/15/08, 1518 NSCLC pts have enrolled. Median F/U is 7.5 mos. Key BL characteristics: 20% ≥75 yrs; 67% adenocarcinoma; 10% ECOG ≥2; 8% brain metastasis; 5% therapeutic AC. The most common 1st-line chemotherapy regimen was carboplatin/paclitaxel (64%). Key safety outcomes and cohort size of subpopulations are in the Table . Conclusions: The safety of BV in subpopulations of pts in ARIES (elderly pts, pts with ECOG PS ≥2, with brain mets at BL, or on therapeutic AC) is generally consistent with safety results from RCTs. Updated outcomes analyses will be presented at the meeting for >1600 pts and subpopulations. [Table: see text] [Table: see text]

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