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'Liquid biopsy' leads to earlier detection of NSCLC treatment resistance
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PHILADELPHIA — A novel regular blood test, known as a “liquid biopsy,” can monitor the presence of EML4-ALK gene fusion rearrangements in patients with non-small cell lung cancer, according to study results presented at the American Association for Cancer Research Annual Meeting.
Real-time monitoring of the EML4-ALK rearrangement status could help clinicians predict patients’ outcomes with crizotinib (Xalkori, Pfizer), researchers said.
“By using the platelets isolated from venous blood specimen collections, we have an opportunity to follow the therapy in real time by determining alterations occurring in the tumor during treatment, and this makes it possible to tailor the therapy for each patient,” Jonas A. Nilsson, PhD, a researcher in the department of radiation sciences at Umeå University in Sweden, said in a press release. “As a compliment to imaging modalities, we may help doctors to be informed on when the tumor starts to regrow, when to switch therapy and whether second-generation ALK inhibitors may be effective.”
Nilsson and colleagues sought to determine the sensitivity and specificity of identifying the EML4-ALK rearrangements, examining the impact of those rearrangements on crizotinib outcomes, and to test the feasibility of monitoring patients throughout their therapy.
The researchers analyzed blood samples from 77 patients with NSCLC who had an identified mutation status, 38 of whom had the EML4-ALK rearrangement within their tumor.
Researchers analyzed EML4-ALK rearrangements by a reverse transcription-polymerase chain reactor in platelets and plasma. Overall, the detection of the EML4-ALK rearrangements demonstrated 100% specificity and 65% sensitivity.
Researchers also were able to evaluate PFS and OS in a subset of 29 patients who received crizotinib.
Patients with a positive EML4-ALK status demonstrated a median PFS of 3.7 months, whereas patients with a negative EML4-ALK status demonstrated a median PFS of 16 months (HR = 3.5; P = .02).
“We showed that if we detected EML4-ALK in the platelet fraction before therapy starts and it does not disappear during treatment, it indicates that the patient is not responding to the therapy, which is associated with shorter time to recurrence and, therefore, other therapies could be tried,” Nilsson said in the release.
Further, the researchers noted that monitoring the rearrangements during therapy was feasible. The test identified crizotinib resistance in one patient who was followed for 2.5 years 2 months prior to imaging confirmation.
“This study shows that platelet-powered diagnostics may add another layer of information to clinicians, and this information can be used to help in the clinical decision-making process,” Nilsson said in the release. “Therefore, the platelet platform is an interesting bio-source for the next generation of liquid biopsies and in the development of personalized health care.” – by Anthony SanFilippo
Reference:
Nilsson JA, et al. Abstract #8728. Presented at: American Association for Cancer Research Annual Meeting; April 18-22, 2015; Philadelphia.
Disclosure: Nilsson reported stock ownership in and a co-founder role with thromboDx BV.
Perspective
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Grace Dy, MD
Clinicians and patients alike have been waiting for less invasive tests that can help in cancer management, such as diagnosis and monitoring of treatment outcomes. This research study assessed the presence of the rare genetic aberration EML4-ALK translocation in blood platelets. This “liquid biopsy” identified 65% of patients with EML4-ALK translocation confirmed using conventional tissue assays. Although not a very sensitive test, researchers showed that in patients who received treatment with crizotinib (Xalkori, Pfizer), this test was able to differentiate patients who are at risk for early disease progression if EML4-ALK continues to be detected in the platelet fraction while on therapy. Conversely, re-emergence of EML4-ALK in the platelets after initial disappearance may predict progression months ahead of radiological disease progression.
Multiple other similar strategies are currently being investigated, such as the use of plasma, urine and pleural effusions in the detection of oncogenic changes that predict for response to therapy. The concept of “liquid biopsy” is an unmet need in the clinical setting. Although further efforts are clearly required to improve on accuracy, validity, sensitivity and specificity of these tests, it is anticipated that, given the pace of technological advances, the liquid biopsy approach will hopefully be ready for routine clinical use to provide complementary information to standard tissue biopsies, and in certain situations to supplant standard tissue biopsies, within the next 5 years or less.
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