Nav: Home

Liquid biopsies in SOLAR-1 trial predict benefit of Alpelisib in PIK3CA-mutant breast cancer

December 06, 2018

Liquid biopsy-based assessment of PIK3CA mutational status served as a better indicator of progression-free survival compared with analysis of tissue biopsy in breast cancer patients enrolled in the phase III clinical trial SOLAR-1, according to data presented at the 2018 San Antonio Breast Cancer Symposium, held Dec. 4-8.

"While the primary endpoint of the SOLAR-1 trial was determined based on PIK3CA mutations in any available tumor tissue, such as archival or fresh tissue, liquid biopsy analysis can be performed on a plasma sample obtained just prior to the initiation of treatment," said Dejan Juric, MD, director of the Termeer Center for Targeted Therapies at the Massachusetts General Hospital Cancer Center. "Our analysis reveals that advanced breast cancer patients with detectable PIK3CA mutations in their blood have a more impressive benefit when alpelisib [a selective PI3K-alpha inhibitor] is added to fulvestrant for their treatment compared to patients with PIK3CA mutations detected in their tissue."

Utilizing information from the SOLAR-1 trial, Juric and colleagues analyzed data from 341 hormone positive, HER2-negative advanced breast cancer patients with PIK3CA mutations, as determined by tissue biopsy, who had received prior endocrine therapy. Patients were randomized to receive either fulvestrant and alpelisib or fulvestrant and placebo. The median follow-up time was 20 months.

In addition to tissue-based analysis, the researchers evaluated progression-free survival (PFS) by PIK3CA mutational status as measured in circulating tumor DNA (ctDNA). PFS was also analyzed by line of metastatic treatment, and by prior exposure to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

While patients with PIK3CA mutations as evaluated in tissue samples had a 35 percent reduction in risk for disease progression, the risk reduction was 45 percent for patients with PIK3CA mutations as evaluated in ctDNA.

"Compared to tissue DNA, circulating tumor DNA is a very easily accessible source of material for mutation profiling," said Juric. "The finding that assessing mutational status via liquid biopsy resulted in even larger clinical benefit compared to tissue biopsy, with improvement of median PFS from 3.7 months to 10.9 months, further highlights the clinical utility of this biospecimen."

Compared with patients in the placebo arm, those who received alpelisib as second line of treatment in the metastatic setting had a 39 percent reduction in risk for disease progression; the risk reduction was 33 percent for those who did not receive prior treatment with CDK4/6 inhibitors. There was also a 52 percent (nonsignificant) reduction in risk for participants who received prior treatment with CDK4/6 inhibitors.

Patients enrolled in the alpelisib arm experienced increased incidences of hyperglycemia, diarrhea, nausea, and rash compared to the placebo arm (65 percent versus 9 percent; 54 percent versus 11 percent; 46 versus 20 percent; and 40 percent versus six percent, respectively).

"PI3K-alpha is important for insulin signaling and PI3K-alpha inhibition results in insulin resistance; hyperglycemia is therefore an on-target effect inextricably linked with the activity of alpelisib," said Juric. "Early detection and serial monitoring of elevated glucose, initiation of appropriate dietary measures, as well as early initiation of metformin and other insulin sensitizers is essential for adequate management of these patients."

Limitations of this study include a small number of patients who received prior treatment with CDK4/6 inhibitors. "Larger studies specifically focused on post-CDK4/6 patients are needed to further characterize the role of alpelisib in this setting," Juric noted.
-end-
The study was sponsored by Novartis. Juric has received scientific advisory board fees from Novartis, Genentech, EMD Serono, Ipsen, and Eisai.

American Association for Cancer Research

Related Disease Progression Articles:

Genetic modifier for Huntington's disease progression identified
A team led by UCL and Cardiff University researchers has developed a novel measure of disease progression for Huntington's disease, which enabled them to identify a genetic modifier associated with how rapidly the disease progresses.
Blood test can predict onset and track progression of Huntington's disease
The first blood test that can predict the onset and progression of Huntington's disease has been identified by a UCL-led study.
Some lung cancer patients benefit from immunotherapy even after disease progression
Some advanced lung cancer patients benefit from immunotherapy even after the disease has progressed as evaluated by standard criteria, according to research presented at the European Lung Cancer Conference (ELCC).
Boosting a cell-protecting protein may help slow Alzheimer's disease progression
A new study of Alzheimer's disease by Fiona Kerr and Linda Partridge at University College London, uses mouse and fruit fly models to show that Keap1, which inhibits the protective protein Nrf2, is a promising target for new preventative drugs for Alzheimer's and other neurodegenerative diseases.
MS treatment that 'resets' immune system may halt disease progression for at least 5 years
A type of treatment for multiple sclerosis that 'resets' the immune system may stop progression of the disease in nearly half of patients.
Researchers show how Lou Gehrig's disease progression could be delayed
A team of biomedical scientists led by researchers at the University of California, Riverside has identified a molecule (123C4) that targets a gene (EphA4 receptor) that plays a critical role in the progression of amyotrophic lateral sclerosis, sometimes known as Lou Gehrig's disease, which affects motor neurons.
New PET imaging technique may help monitor neurological disease progression
In Alzheimer's disease and Parkinson's disease, loss of the sense of smell often precedes classical symptoms of cognitive or motor dysfunction.
Study challenges model of Alzheimer's disease progression
Researchers provide unprecedented evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment in people with Alzheimer's disease.
Antibiotics weaken Alzheimer's disease progression through changes in the gut microbiome
Long-term treatment with broad spectrum antibiotics decreased levels of amyloid plaques, a hallmark of Alzheimer's disease, and activated inflammatory microglial cells in the brains of mice in a new study by neuroscientists from the University of Chicago.
MicroRNAs help to predict disease progression in brain tumors
Scientists at the Helmholtz Zentrum M√ľnchen and the Ludwig Maximilians University of Munich have developed a new method of predicting disease progression in gliobastoma patients who have undergone standard treatment.

Related Disease Progression Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Don't Fear Math
Why do many of us hate, even fear math? Why are we convinced we're bad at it? This hour, TED speakers explore the myths we tell ourselves and how changing our approach can unlock the beauty of math. Guests include budgeting specialist Phylecia Jones, mathematician and educator Dan Finkel, math teacher Eddie Woo, educator Masha Gershman, and radio personality and eternal math nerd Adam Spencer.
Now Playing: Science for the People

#518 With Genetic Knowledge Comes the Need for Counselling
This week we delve into genetic testing - for yourself and your future children. We speak with Jane Tiller, lawyer and genetic counsellor, about genetic tests that are available to the public, and what to do with the results of these tests. And we talk with Noam Shomron, associate professor at the Sackler School of Medicine at Tel Aviv University, about technological advancements his lab has made in the genetic testing of fetuses.