Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC

Hellmann, Matthew D.; Nabet, Barzin Y.; Rizvi, Hira; Chaudhuri, Aadel A.; Wells, Daniel K.; Dunphy, Mark; Chabon, Jacob J.; Liu, Chih Long; Hui, Angela B.; Arbour, Kathryn C.; Luo, Jia; Preeshagul, Isabel R.; Moding, Everett J.; Almanza, Diego; Bonilla, Rene F.; Sauter, Jennifer L.; Choi, Hyejin; Tenet, Megan; Abu-Akeel, Mohsen; Plodkowski, Andrew J.; Johnston, Rocio Perez; Yoo, Christopher H.; Ko, Ryan B.; Stehr, Henning; Gojenola, Linda; Wakelee, Heather A.; Padda, Sukhmani K.; Neal, Joel W.; Chaft, Jamie E.; Kris, Mark G.; Rudin, Charles M.; Merghoub, Taha; Li, Bob T.; Alizadeh, Ash A.; Diehn, Maximilian

doi:10.1158/1078-0432.ccr-19-3418

Cited by 77 publications

(49 citation statements)

References 35 publications

(59 reference statements)

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“…A recent study of ctDNA in long-term responders to PD-(L)1 blockade suggest that ctDNA testing can be used to predict the risk of eventual progression. In this study, 31 NSCLC patients with long-term benefit to PD-(L)1 blockade (defined as PFS ongoing > 1 year) were included (26,27). The median duration of ICPI therapy was 20.4 months (range: 1.7-48.1 months).…”

Section: Can We Use Predictors Of Long-term Benefit To Determine the mentioning

confidence: 99%

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

2020

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Immune checkpoint inhibitors (ICPIs) have revolutionized the management and prognosis of fit patients with advanced non-small cell lung cancer (NSCLC). Recently, the publication of 5-year survival rates has cemented the role of ICPIs in NSCLC. An ongoing challenge is to determine the optimal treatment duration to find the balance between efficacy, toxicity and cost. From the onset of ICPI trials, different durations were used, ranging from treatment until progression or toxicity, to fixed durations of 2 years. Subsequently, exploratory analyses from a 1-year fixed duration trial failed to change practice. There are, to date, no adequately powered prospective trials addressing this important question. With today's severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic, more than ever, the question resurfaces with added factors tilting the already shaky therapeutic balance. Here, we will discuss current data regarding ICPI treatment duration and incorporate this into the context of the ongoing pandemic. We conclude with a discussion of pragmatic approaches, should physicians be unable to continue standard therapy.

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Section: Can We Use Predictors Of Long-term Benefit To Determine the mentioning

confidence: 99%

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

2020

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“…Plasma was separated by centrifugation at 1600 g for 20 minutes within 2 hours of being drawn from the patient. 13 Supernatants were stored as 2 mL aliquots at −80°C. Leukocytes, for control DNA, were washed and stored at −80°C.…”

Section: Sample Collectionmentioning

confidence: 99%

Monitoring treatment response and disease progression in myeloma with circulating cell‐free DNA

Deshpande

Tytarenko

Wang

et al. 2020

European J of Haematology

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Circulating cell‐free DNA (cfDNA) has the potential to capture spatial genetic heterogeneity in myeloma (MM) patients. We assessed whether cfDNA levels vary according to risk status defined by the 70 gene expression profile (GEP70). cfDNA levels in 77 patients were significantly higher in the GEP70 high‐risk (HR) group compared to the low‐risk (LR) group and correlated weakly with clinical markers including lactate dehydrogenase, β2‐microglobulin, and ISS. Patients with high cfDNA levels were associated with a worse PFS (hazard ratio 6.4; 95% CI of ratio 1.9‐22) and OS (hazard ratio 4.4; 95% CI of ratio 1.2‐15.7). Circulating tumor DNA (ctDNA) was elevated in the HR group and ctDNA correlated strongly with GEP70 risk score (Spearman r = .69, P = .0027). cfDNA concentrations were significantly elevated between days 3‐5 after chemotherapy before falling back to baseline levels. ctDNA in two patients showed a similar spike in levels between days 3 and 5 after chemotherapy with a concomitant increase in allele fraction of KRAS mutations. We assessed cfDNA levels in 25 patients with smoldering myeloma with serial samples and showed increased allele fraction of mutated KRAS at progression in cfDNA. Our study shows that cfDNA is a dynamic tool to capture genetic events in myeloma.

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“…Recently, Hellman et al hypothesized that ctDNA analysis of responders to immune checkpoint inhibitors may predict the long-term clinical benefit of this strategy [18]. This study included 31 advanced NSCLC patients still responding after at least 12 months of an immune checkpoint inhibitor representing 20% of the entire population.…”

Section: Identification Of Completely Eradicated Disease In Long Respmentioning

confidence: 99%

“…The duration of immunotherapy in long responder patients after two years of treatment is debated. ctDNA could be useful in this context to differentiate patients whose disease was cleared or not by the treatment and offer them different treatment strategies [18].…”

Section: Introductionmentioning

confidence: 99%

Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

Gobbini

Swalduz

Levra

et al. 2020

Cancers

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Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is limiting. The clinical relevance of tumor genotyping through analysis of ctDNA is now widely recognized at all steps of the clinical evaluation process in metastatic non-small cell lung cancer (NSCLC) patients. ctDNA analysis through liquid biopsy has recently gained increasing attention as well in the management of early and locally advanced, not oncogene-addicted, NSCLC. Its potential applications in early disease detection and the response evaluation to radical treatments are promising. The aim of this review is to summarize the landscape of liquid biopsies in clinical practice and also to provide an overview of the potential perspectives of development focusing on early detection and screening, the assessment of minimal residual disease, and its potential role in predicting response to immunotherapy. In addition to available studies demonstrating the clinical relevance of liquid biopsies, there is a need for standardization and well-designed clinical trials to demonstrate its clinical utility.

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Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC

Cited by 77 publications

References 35 publications

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

Rethinking the Optimal Duration of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer Throughout the COVID-19 Pandemic

Monitoring treatment response and disease progression in myeloma with circulating cell‐free DNA

Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

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