A large prospective, randomized clinical trial in patients with advanced breast cancer has found that the use of liquid biopsy blood tests for early detection of a treatment-resistance mutation, followed by a switch to a new type of treatment, substantially extends the period of tumor control compared to standard care.
The SERENA-6 study, published June 1 in the New England Journal of Medicine and presented concurrently at the annual meeting of the American Society for Clinical Oncology, was conducted at multiple medical centers, principally in Europe, East Asia and the United States, including at Weill Cornell Medicine and three affiliated NewYork-Presbyterian campuses: NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian Brooklyn Methodist Hospital, and NewYork-Presbyterian Queens. It is one of the first demonstrations that treatment switching guided by liquid biopsy results brings better outcomes for patients.
"The main message here is that liquid biopsy technology allows us to intervene sooner when the tumor burden is lower and the chance of a good outcome is higher," said study co-author Dr. Massimo Cristofanilli, professor of medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
Dr. Cristofanilli, an expert on the use of liquid biopsy technology for cancer monitoring and early cancer detection, helped design and oversee the SERENA-6 study as a member of its steering committee.
The study, which was sponsored by Astra Zeneca, enrolled patients with advanced forms of estrogen receptor (ER) positive, HER2 receptor-negative breast cancer, which is driven by the overactivity of growth-promoting estrogen receptors on tumor cells. Standard treatment includes drugs called aromatase inhibitors that block the production of ER-stimulating estrogen hormones. However, tumors treated this way often start growing and spreading again because they develop mutations in the ESR1 gene that keep estrogen receptors active even when estrogen hormone levels are low or absent.
The trial was set up to determine if patients would benefit from early detection of ESR1 mutations with liquid biopsy-type blood tests, followed by an immediate switch to an experimental new breast cancer drug called camizestrant, which reduces the number of estrogen receptors.
The researchers screened more than 3,300 patients at 264 different clinical sites in 23 countries. The 315 who had detectable ESR1 mutations but no symptomatic or medical imaging evidence of tumor progression were randomly assigned to stop taking an aromatase inhibitor and start taking camizestrant, or to stick to standard treatment including an aromatase inhibitor.
The results showed that patients who switched to camizestrant tended to have a longer period of tumor non-progression (median 16.0 months vs. 9.2 months), and a much longer time to deterioration in their overall health status and quality of life (median 23.0 months vs. 6.4 months).
The researchers considered these differences to be both statistically significant and clinically meaningful. Camizestrant also was well tolerated, with low rates of treatment discontinuation.
Dr. Cristofanilli, who is also the scientific director of the Englander Institute for Precision Medicine and the associate director of precision oncology at the Sandra and Edward Meyer Cancer Center, said that he expects the strategy demonstrated in this study to be applicable more generally when doctors monitor for ER-positive breast cancer recurrence after treatment. He noted as well that not only breast cancer but also many other cancer types have potential treatment-resistance mutations that can be detected early with liquid biopsy techniques.
