“Circulating tumor DNA (ctDNA) can help differentiate what is known as pseudoprogression from true progression of disease in patients with melanoma who are treated with programmed death 1 (PD-1) inhibitors, according to a new study. It also showed that ctDNA could be used as a powerful biomarker to predict long-term outcomes.
” ‘Pseudoprogression, a response that occurs after the initial development of new lesions or an increase in the size of target lesions, occurs in up to 10% of patients treated with PD-1 antibodies,’ wrote study authors led by Jenny H. Lee, MBBS, of Macquarie University in Sydney, Australia. ‘Confirmation of pseudoprogression requires subsequent imaging, imposing an ongoing challenge.’ ”
“In patients with hormone receptor (HR)-positive advanced breast cancer and no prior endocrine therapy who were positive for a gene signature-based biomarker indicating androgen receptor (AR)-signaling, the addition of enzalutamide (Xtandi) to exemestane was found to significantly improve progression-free survival (PFS) from 4 months to 16.5 months.
“Moreover, the phase II trial showed no effect of enzalutamide on PFS in the overall cohort of patients nor in the biomarker-positive population who received prior endocrine therapy, said Denise Yardley, MD, at the 2017 San Antonio Breast Cancer Symposium.”
“The boom of blood-based biomarkers has led to a turning point in clinical practice for physicians treating patients with non–small cell lung cancer (NSCLC). While tissue biopsies remain the standard approach, plasma assays—if positive—can direct patients to a first-line targeted treatment quicker.
” ‘Blood-based testing does have a role in patients with NSCLC,’ said Leora Horn, MD, MSc. ‘The blood can be potentially used as a surrogate for markers for directing for therapy. But if blood testing is negative, it is not enough to say that a patient is not positive. Those patients do need to go on to get a biopsy.’ ”
“Updates to the National Comprehensive Cancer Network (NCCN) guidelines for the management of advanced non–small cell lung cancer (NSCLC) stress the importance of multiplexed biomarker testing at diagnosis to aid in the selection of appropriate first-line and subsequent lines of therapy, said presenters at the 2017 NCCN Annual Conference.
“The latest version of the guidelines recommends that PD-L1, in addition to molecular analysis, be employed as a biomarker to direct initial therapy, with ≥50% expression established as the threshold for a positive result. The PD-L1 test ‘decides whether a patient has enough of the marker to warrant initial immunotherapy,’ said presenter Gregory J. Riely, MD, PhD.”
“By assessing plasma androgen receptor (AR) gene status assessment with multiplex droplet digital PCR (ddPCR), European researchers could predict which patients with castration-resistant prostate cancer (CRPC) were most likely to have poorer outcomes while undergoing targeted therapy, according to results from the PREMIER trial published in the Annals of Oncology.
“Researchers said there was a ‘significant association’ for AR gain and poorer overall survival (OS) for both chemotherapy-naïve patients (HR, 3.98; 95% CI, 1.75-9.10; P <.001) and patients previously treated with docetaxel (HR, 3.81; 95% CI, 2.28-6.37; P <.001). AR gain was also associated with poorer OS for chemotherapy-naïve patients treated with enzalutamide (Xtandi) or abiraterone acetate (Zytiga; HR, 2.18; 95% CI, 1.08-4.39; P = .03) and for patients previously treated with docetaxel (HR, 1.95; 95% CI, 1.23-3.11; P = .01).”
“Results from a prospective clinical trial showed that a blood test looking at specific biomarkers was able to detect recurrences of lung cancer an average of six months before conventional imaging methods found evidence of recurrence. In the largest prospective clinical trial to date of circulating tumor cells (CTC) as biomarkers for locally advanced lung cancer, the findings indicate that blood tests potentially can be used in conjunction with CT and PET/CT scans to guide personalized treatment planning for patients with non-small cell lung cancer (NSCLC). The study will be presented today at the 2017 Multidisciplinary Thoracic Cancers Symposium.”
“A prostate-specific antigen (PSA) nadir (the lowest level a PSA drops following treatment) greater than 0.5 ng/mL following radiation and androgen deprivation therapy seems to identify men prior to PSA failure who are at high-risk for death, and would thus require more aggressive treatment for their prostate cancer, according to the results of a recent study in JAMA Oncology.
“The study looked at data from a randomized trial of 206 men treated with either radiation or radiation plus 6 months of hormonal therapy and compared early markers of prostate cancer death to identify men at risk of dying early.”
“Detecting AR-V7 positive tumor cells circulating in the blood of an advanced prostate cancer patient predicts that he will not only fail the commonly-prescribed androgen receptor signaling inhibitors (ARSI), abiraterone and enzalutamide, but that he will survive significantly longer if treated with a taxane based chemotherapy regimen.
“This discovery, published today in JAMA Oncology, emerged from a study of 161 progressing metastatic castration-resistant prostate cancer (mCRPC) patients about to start an FDA approved ARSIs or taxane as a first, second or third line treatment at Memorial Sloan Kettering Cancer Center (MSK). Blood samples taken along with those routinely collected from the patients were analyzed on the Epic Sciences’ liquid biopsy platform for circulating tumor cells (CTCs) with the AR-V7 biomarker. Overall, almost 20% of patients had AR-V7 positive CTCs.
” ‘The percentage of men that responds to ARSIs is highest in the first line setting, decreasing steadily as more treatments are given. We found that a novel liquid biopsy for AR-V7 was able to identify, with specificity, patients who will not benefit from these therapies and should instead start chemotherapy independent of the line of therapy being administered,’ said Howard Scher, M.D., chief of the genitourinary oncology services at MSK and corresponding author for the study.”
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“A study by J. William Harbour, M.D., Associate Director for Basic Research and leader of the Eye Cancer Site Disease Group at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, and colleagues, published today in Clinical Cancer Research, details the discovery of a biomarker that puts patients at a higher risk for metastasis of uveal melanoma.
“Among uveal melanomas categorized as class 1, those with high levels of the biomarker PRAME mRNA were more likely to metastasize than those with low levels of PRAME mRNA, indicating that patients with this biomarker be monitored more closely for metastatic disease.
“The estimated five-year rate of metastasis was 0 percent for PRAME mRNA–low class 1 uveal melanomas and 38 percent for PRAME mRNA–high class 1 uveal melanomas. This research builds upon Harbour’s identification of class 1 and 2 uveal melanomas in 2004.”