Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer

Steendam, Christi M.J.; Veerman, G.; Pruis, Melinda A.; Atmodimedjo, Peggy N.; Paats, Marthe S.; Leest, Cor van der; Thüsen, Jan H. von der; Yick, David C Y; Hoop, Esther Oomen–de; Koolen, Stijn L.W.; Dinjens, Winand N.M.; Schaik, Ron H.N. van; Mathijssen, Ron H.J.; Aerts, Joachim; Dubbink, Hendrikus J.; Dingemans, Anne‐Marie C.

doi:10.3390/cancers12113179

Cited by 13 publications

(21 citation statements)

References 43 publications

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“…Circulating tumor DNA (ctDNA) analysis has revolutionized care in patients on targeted treatment (60,61). In the Gomez trial decrease in ctDNA was observed in the patients treated with local consolidative treatment (62).…”

Section: Future Perspectivesmentioning

confidence: 99%

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review

Mentink¹,

Paats²,

Dumoulin³

et al. 2021

Transl Lung Cancer Res

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In this review, the concept of (synchronous) oligometastatic disease in patients with nononcogene-driven non-small cell lung cancer (NSCLC) will be placed in the context of tumor biology and metastatic growth patterns. We will also provide considerations for clinical practice and future perspectives, which will ultimately lead to better patient selection and oligometastatic disease outcome. Background:The treatment landscape of metastasized NSCLC has moved from "one-size fits all" to a personalized approach. Prognosis has traditionally been poor but new treatment options, such as immunotherapy and targeted therapy, brighten future perspectives. Another emerging development is the recognition of patients with so-called "oligometastatic" state of disease. Oligometastatic disease has been recognized as a distinct clinical presentation in which the tumor is stated to be early in its evolution of metastatic potential. It is suggested that this stage of disease has an indolent course, comes with a better prognosis and therefore could be considered for radical multimodality treatment.Methods: Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases, hand searches, and authoritative texts.Conclusions: Oligometastatic NSCLC is a broad spectrum disease, with a variable prognosis. Although the biology and behavior of "intermediate state" of metastatic disease are not fully understood, there is evidence that a subgroup of patients can benefit from local radical treatment when integrated into a multimodality regime. The consensus definition of oligometastatic NSCLC, including accurate staging, may help to uniform future trials. The preferable treatment strategy seems to sequential systemic treatment with subsequent local radical treatment in patients with a partial response or stable disease. Prognostic factors such as N-stage, number and site of distant metastases, tumor volume, performance status, age, and tumor type should be considered. The local radical treatment strategy has to be discussed in a multidisciplinary team meeting, taking into account patient characteristics and invasiveness of the procedure. However, many aspects remain to be explored and learned about the cancer biology and characteristics of intermediate state tumors.

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Section: Future Perspectivesmentioning

confidence: 99%

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review

Mentink¹,

Paats²,

Dumoulin³

et al. 2021

Transl Lung Cancer Res

Self Cite

View full text Add to dashboard Cite

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“…Molecular targeted therapy has been reported to have an excellent outcome for driver gene mutant advanced non‐small cell lung cancer (NSCLC) patients, 1–3 but the effectiveness is greatly different among patients 4–7 . How to achieve efficacy stratification is important for implementing individualized precision treatment and prolonging the overall survival.…”

Section: Introductionmentioning

confidence: 99%

“…Molecular targeted therapy has been reported to have an excellent outcome for driver gene mutant advanced non‐small cell lung cancer (NSCLC) patients, 1 , 2 , 3 but the effectiveness is greatly different among patients. 4 , 5 , 6 , 7 How to achieve efficacy stratification is important for implementing individualized precision treatment and prolonging the overall survival. Radiological imaging fails to reflect clonal evolution at the molecular level timely.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR‐TKI treatment in advanced non‐small cell lung cancer

Zheng

Wang

et al. 2022

Thoracic Cancer

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Background: Circulating tumor DNA (ctDNA) has made a breakthrough as an early biomarker in operable early-stage cancer patients. However, the function of ctDNA combined with cell-free DNA (cfDNA) as a predictor in advanced non-small cell lung cancer (NSCLC) remains unknown. Here, we explored its potential as a biomarker for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced NSCLC. Methods: A retrospective analysis was undertaken. Plasma collected from 51 patients with advanced NSCLC prior to and serially after starting treatment with EGFR-TKIs was analyzed by next-generation sequencing (NGS). The performance of ctDNA, cfDNA, and combining ctDNA with cfDNA were evaluated for their ability to predict survival outcomes. Results: Patients with early undetectable ctDNA and increasing cfDNA had a markedly better progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.001) than those with early detectable ctDNA and decreasing cfDNA. Patients with early ctDNA clearance were more likely to have the ctDNA persistent clearance (p = 0.006). The early clearance rate of ctDNA in the normal carcinoembryonic antigen (CEA) group was significantly higher than in the low and high groups (p = 0.028). Patients with greater CEA decline had a higher early clearance rate of ctDNA than those with minor CEA change (p = 0.016). Conclusions: We based this study on ctDNA and cfDNA, explored its prognostic predictive ability, and combined CEA to monitor EGFR-TKI efficacy. This study may provide new perspectives and insights into the precise treatment strategies for NSCLC patients. K E Y W O R D Snon-small cell lung cancer, epidermal growth factor receptor tyrosine kinase inhibitors, circulating tumor DNA, cell-free DNA, carcinoembryonic antigen

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“…The START-TKI study 12 is a real-life, prospective, multi-center cohort study. Patients who are treated with SMKIs at the Erasmus Medical Centre Cancer Institute in Rotterdam and the Amphia Hospital in Breda, both in the Netherlands, between January 2017 and September 2021, were asked to participate in this study.…”

Section: Methodsmentioning

confidence: 99%

Improving the tolerability of osimertinib by identifying its toxic limit

et al. 2022

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Background: Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction. Methods: In this real-life prospective cohort study, patients with NSCLC treated with osimertinib were followed for severe toxicity (grade ⩾3 toxicity, dose reduction or discontinuation, hospital admission, or treatment termination). Blood for pharmacokinetic analyses was withdrawn during every out-patient visit. Primary endpoint was the correlation between osimertinib clearance (exposure) and severe toxicity. Secondary endpoint was the exposure–efficacy relationship, defined as progression-free survival (PFS) and overall survival (OS). Results: In total, 819 samples from 159 patients were included in the analysis. Multivariate competing risk analysis showed osimertinib clearance ( c.q. exposure) to be significantly correlated with severe toxicity (hazard ratio 0.93, 95% CI: 0.88–0.99). An relative operating characteristic curve showed the optimal toxic limit to be 259 ng/mL osimertinib. A 50% dose reduction in the high-exposure group, that is 25.8% of the total cohort, would reduce the risk of severe toxicity by 53%. Osimertinib exposure was not associated with PFS nor OS. Conclusion: Osimertinib exposure is highly correlated with the occurrence of severe toxicity. To optimize tolerability, patients above the toxic limit concentration of 259 ng/mL could benefit from a preventive dose reduction, without fear for diminished effectiveness.

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Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer

Cited by 13 publications

References 43 publications

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review

Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR‐TKI treatment in advanced non‐small cell lung cancer

Improving the tolerability of osimertinib by identifying its toxic limit

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