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

December 6, 2018, American Association for Cancer Research

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 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 ," 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 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 resulted in even larger clinical benefit compared to 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 are needed to further characterize the role of alpelisib in this setting," Juric noted.

Explore further: Targeting specific genomic mutation in breast cancer improves outcomes, first study shows

Related Stories

Targeting specific genomic mutation in breast cancer improves outcomes, first study shows

October 22, 2018
Targeting a common mutation in patients with hormone receptor positive (HR+) HER2 negative (HER2-) advanced breast cancer with the alpha-specific phosphatidylinositol-3-kinase (PI3K) inhibitor alpelisib significantly improves ...

Circulating tumor cell count could help choose treatment for metastatic breast cancer patients

December 6, 2018
Circulating tumor-cell (CTC) count could be used to choose hormone therapy or chemotherapy as frontline treatment for patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer, according ...

New option for women with advanced breast cancer resistant to hormone therapy

October 22, 2018
Treatment with the cyclin dependent kinase (CDK) 4/6 inhibitor palbociclib achieves a clinically meaningful improvement in overall survival in patients with hormone receptor positive (HR+) human epidermal growth factor receptor-2 ...

Drug combination slows growth of most common type of advanced breast cancer

June 4, 2018
The combination of taselisib and fulvestrant has shown to slow the growth of cancer in post-menopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2) negative, PIK3CA-mutant, inoperable, ...

Liquid biopsy can assess therapeutic response of pediatric brain tumors

November 30, 2018
(HealthDay)—A liquid biopsy using blood or cerebrospinal fluid (CSF) can effectively quantify changes in mutation levels among pediatric patients being treated for diffuse midline gliomas (DMGs), according to a study recently ...

Blood test identifies more treatable cancer mutations than tissue biopsy alone

October 11, 2018
In one of the largest clinical studies to ever examine the impact of using a blood test to detect treatable mutations in non-small cell lung cancer (NSCLC), researchers from the Abramson Cancer Center of the University of ...

Recommended for you

Treatment shown to improve the odds against bone marrow cancer

December 15, 2018
Hope has emerged for patients with a serious type of bone marrow cancer as new research into a therapeutic drug has revealed improved outcomes and survival rates.

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Lethal combination: Drug cocktail turns off the juice to cancer cells

December 12, 2018
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth—this was discovered by researchers from the University of Basel's Biozentrum two years ago. In a follow-up study, ...

Combining three treatment strategies may significantly improve melanoma treatment

December 12, 2018
A study by a team led by a Massachusetts General Hospital (MGH) investigator finds evidence that combining three advanced treatment strategies for malignant melanoma—molecular targeted therapy, immune checkpoint blockade ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.