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CHICAGO – Monitoring of circulating tumor DNA during advanced melanoma treatment may help identify patients likely to benefit from dabrafenib alone or with trametinib, according to a data badysis of the COMBI-d phase test 3 presented at the ASCO Annual Meeting.
This appeared particularly true in patients with elevated lactate dehydrogenase initially, a prognostic factor established in this context.
"Our study offers strong evidence that tracking this genetic information can be useful in identifying patients whose cancer contracts and who survive longer as a result of a particular drug treatment," senior researcher of the group. ;study. David Polsky, MD, PhD, Alfred W. Kopf, MD, professor of dermatological oncology at NYU Langone Health, said in a press release.
The badysis included 345 patients with metastatic or unresectable melanoma treated with dabrafenib (Tafinlar, Novartis) alone or with trametinib (Mekinist, Novartis) in Phase III COMBI-d and BRAF Plasma measurements of V600E / V600K circulating tumor DNA plasma (cDNA) at the beginning and at the 4th week.
The researchers evaluated the plasma samples using mutation-specific droplet digital polymerase chain reaction badays (Bio-Rad Laboratories), categorizing the results as positive or negative using a 0.25 copy threshold. / mL.
Most patients (n = 320, 92.7%) had a detectable tDNA at baseline. However, basic cDNA measurements were not badociated with survival.
Almost all patients experienced a decrease in cDNA after 4 weeks of treatment.
Of the 224 patients with 4-week measurements, 128 remained positive for ctDNA and 96 were negative. Patients who remained positive had a significantly shorter median PFS (7.4 months vs. 13 months, HR = 1.68, 95% CI, 1.24-2.27) and one OS (15.3 vs. 27 months, 9 months, HR = 1.64, 95% CI, 1.2-2.25) than patients who became negative for cDNA.
A total of 201 patients had a baseline detectable cDNA that could be compared to 4-week matched measures. Among them, 121 (60%) remained positive for ctAD at 4 weeks and 80 (40%) were negative. Those who became negative had a significant improvement in median PFS (12.9 months vs. 7.1 months, HR = 0.55, 95% CI, 0.39-0.76) and median SO ( 28.2 months vs 14.6 months, HR = 0.56, 95% CI, 0.4-0.79).
The researchers also compared cDNA results in patients with low lactate dehydrogenase (n = 143) and high lactate dehydrogenase (n = 81).
Of those with a high lactate dehydrogenase initially, 64 remained positive and 17 were negative for ctDNA. Among people whose lactate dehydrogenase was initially weak, 64 remained positive and 79 became negative for cDNA.
Patients with a high lactate dehydrogenase initially showed a particularly significant benefit if they became negative for ct DNA (median SSP for ct + positive / negative DNA, 5.5 months vs. 10, 3 months, HR = 1.99, 95% CI, 1.08 to 3.64, median OS, 10.8 months vs 21.1 months, HR = 2.38, 95% CI, 1.24-4, 54).
The corresponding differences in patients with low lactate dehydrogenase did not reach statistical significance.
Typically, patients with melanoma are screened for disease progression every three months. However, this ctDNA blood test badysis could allow more frequent monitoring, with results readily available, according to Polsky.
The researchers then plan to badyze this approach over a longer period of time and provide for a clinical trial that would determine whether treatment decision-making based on ctDNA monitoring improves survival outcomes.
"If additional tests prove successful, check the blood samples BRAF could tell us quickly whether or not we need to adapt the patient's treatment plan, "he said in a press release. – by Alexandra Todak
Reference:
Syeda MM et al. Abstract 9510. Presented at: ASCO Annual Meeting; May 31 to June 4, 2019; Chicago.
Disclosures: Polsky reports consulting / consulting roles with Molecular® and Novartis, research funds at Bio-Rad Laboratories and Novartis, and travel expenses for Bio-Rad Laboratories. Please consult the summary for the relevant financial information of all other authors.
CHICAGO – Monitoring of circulating tumor DNA during advanced melanoma treatment may help identify patients likely to benefit from dabrafenib alone or with trametinib, according to a data badysis of the COMBI-d phase test 3 presented at the ASCO Annual Meeting.
This appeared particularly true in patients with elevated lactate dehydrogenase initially, a prognostic factor established in this context.
"Our study offers strong evidence that tracking this genetic information can be useful in identifying patients whose cancer contracts and who survive longer as a result of a particular drug treatment," senior researcher of the group. ;study. David Polsky, MD, PhD, Alfred W. Kopf, MD, professor of dermatological oncology at NYU Langone Health, said in a press release.
The badysis included 345 patients with metastatic or unresectable melanoma treated with dabrafenib (Tafinlar, Novartis) alone or with trametinib (Mekinist, Novartis) in Phase III COMBI-d and BRAF Plasma measurements of V600E / V600K circulating tumor DNA plasma (cDNA) at the beginning and at the 4th week.
The researchers evaluated the plasma samples using mutation-specific droplet digital polymerase chain reaction badays (Bio-Rad Laboratories), categorizing the results as positive or negative using a 0.25 copy threshold. / mL.
Most patients (n = 320, 92.7%) had a detectable tDNA at baseline. However, basic cDNA measurements were not badociated with survival.
Almost all patients experienced a decrease in cDNA after 4 weeks of treatment.
Of the 224 patients with 4-week measurements, 128 remained positive for ctDNA and 96 were negative. Patients who remained positive had a significantly shorter median PFS (7.4 months vs. 13 months, HR = 1.68, 95% CI, 1.24-2.27) and one OS (15.3 vs. 27 months, 9 months, HR = 1.64, 95% CI, 1.2-2.25) than patients who became negative for cDNA.
A total of 201 patients had a baseline detectable cDNA that could be compared to 4-week matched measures. Among them, 121 (60%) remained positive for ctAD at 4 weeks and 80 (40%) were negative. Those who became negative had a significant improvement in median PFS (12.9 months vs. 7.1 months, HR = 0.55, 95% CI, 0.39-0.76) and median SO ( 28.2 months vs 14.6 months, HR = 0.56, 95% CI, 0.4-0.79).
The researchers also compared cDNA results in patients with low lactate dehydrogenase (n = 143) and high lactate dehydrogenase (n = 81).
Of those with a high lactate dehydrogenase initially, 64 remained positive and 17 were negative for ctDNA. Among people whose lactate dehydrogenase was initially weak, 64 remained positive and 79 became negative for cDNA.
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Patients with a high lactate dehydrogenase initially showed a particularly significant benefit if they became negative for ct DNA (median SSP for ct + positive / negative DNA, 5.5 months vs. 10, 3 months, HR = 1.99, 95% CI, 1.08 to 3.64, median OS, 10.8 months vs 21.1 months, HR = 2.38, 95% CI, 1.24-4, 54).
The corresponding differences in patients with low lactate dehydrogenase did not reach statistical significance.
Typically, patients with melanoma are screened for disease progression every three months. However, this ctDNA blood test badysis could allow more frequent monitoring, with results readily available, according to Polsky.
The researchers then plan to badyze this approach over a longer period of time and provide for a clinical trial that would determine whether treatment decision-making based on ctDNA monitoring improves survival outcomes.
"If additional tests prove successful, check the blood samples BRAF could tell us quickly whether or not we need to adapt the patient's treatment plan, "he said in a press release. – by Alexandra Todak
Reference:
Syeda MM et al. Abstract 9510. Presented at: ASCO Annual Meeting; May 31 to June 4, 2019; Chicago.
Disclosures: Polsky reports consulting / consulting roles with Molecular® and Novartis, research funds at Bio-Rad Laboratories and Novartis, and travel expenses for Bio-Rad Laboratories. Please consult the summary for the relevant financial information of all other authors.
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