Mafalda Oliveira, MD, PhD, on Camizestrant vs Fulvestrant in Advanced Breast Cancer: New Phase II Results
2022 San Antonio Breast Cancer Symposium
Mafalda Oliveira, MD, PhD, of Spain’s Vall d’Hebron University Hospital and Institute of Oncology, discusses findings from the SERENA-2 trial, which compared the next-generation selective estrogen receptor degrader camizestrant to fulvestrant in patients with hormone receptor–positive, HER2-negative breast cancer. Camizestrant, which can be taken as a daily pill (as opposed to fulvestrant, which must be given via injection), improved progression-free survival by up to 42% (Abstract GS3-02).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
SERENA-2 is a randomized phase two trial of two doses of camizestrant, a novel oral selective ER degrader, versus fulvestrant in patients with ER-positive, HER2-negative metastatic breast cancer that had received prior treatment with endocrine therapy. The reason we designed this study is to test this novel endocrine therapy, camizestrant, an oral SERD that degrades and inhibits more potently the estrogen receptor with respect to the current endocrine therapies.
So SERENA-2 enrolled patients that were postmenopausal, that had to have progressed to prior endocrine therapy, could have received up to one line of endocrine therapy in the metastatic setting and one line of chemotherapy in the metastatic setting, and could have measurable or evaluable disease. And the patients were stratified according to prior treatment with CDK4/6 inhibitors and the presence of lung or liver metastasis, and were randomized to receive camizestrant at three doses, 75 milligrams, 150 milligrams or 300 milligrams, or the current standard of care, fulvestrant.
The arm of camizestrant 300 milligrams was discontinued early due to strategic reasons in the absence of toxicity concerns. Now, 240 patients were included in the trial, all postmenopausal, all with ER-positive breast cancer, and about 20% of the patients had received prior chemotherapy in the metastatic setting. And we designed the trial to include a population of patients, 50% of them had to received prior CDK4/6 inhibitors and that is exactly what happened. About 58% of patients had visceral metastasis lung or liver metastasis, and about 35% of the patients had ESR1 mutation identified in plasma at baseline.
Now the primary endpoint of the trial was progression free survival according to the investigator assessment and camizestrant both at 75 milligram and 150 milligram improved progression free survival in comparison with fulvestrant. The hazard ratio for the 75 milligram comparison was 0.58 with the median PFS for camizestrant of 7.2 months compared with 3.7 months for fulvestrant. And the hazard ratio for camizestrant 150 was at 0.67 with 7.7 months for camizestrant 150 compared to fulvestrant.
The improvement of PFS of camizestrant when compared with fulvestrant was also apparent in important subgroups of patients, like patients previously treated with CDK4/6 inhibitors, patients with lung or liver metastasis, patients with the presence of ESR1 mutation, and patients with evidence of ER-driven disease. A very important point is that this treatment was very well tolerated. Drug discontinuations, drug reductions due to adverse events were very infrequent across all the population of the trial. The most frequent adverse events associated with camizestrant were photopsia, bradycardia, asthenia, and arthralgia. But most of these adverse events were grade one. So grade one bradycardia means it's perfectly asymptomatic. The patient does not complain of any symptom. And the photopsia was very well tolerated because patients could continue with their daily activities.
So in conclusion, in summary, SERENA-2 met its primary endpoint. It is the first evidence that range of doses of an oral SERD, in this case camizestrant, is superior in terms of progression free survival respect to the standard of care, fulvestrant, in patients with ER-positive, HER2-negative metastatic breast cancer that had received prior endocrine therapy. Currently, there are two trials on going that are testing camizestrant in the first-line setting. These are SERENA-4 and SERENA-6, and these trials will build more evidence regarding the activity of this new drug for patients with ER-positive breast cancer.
Erica L. Mayer, MD, PhD, of Dana-Farber Cancer Institute, discusses findings from the PACE study of patients with endocrine- and CDK4/6 inhibitor–pretreated estrogen receptor–positive/HER2-negative metastatic breast cancer who were randomly assigned to fulvestrant alone; fulvestrant and palbociclib; or fulvestrant, palbociclib, and avelumab. Combining palbociclib with fulvestrant beyond disease progression on a prior CDK4/6 inhibitor regimen did not improve progression-free survival compared with fulvestrant alone. A longer progression-free survival when a PD-L1 inhibitor was added to fulvestrant and palbociclib deserves further study. A baseline circulating tumor DNA analysis suggests that the potential benefit of palbociclib after progression on a prior CDK4/6 inhibitor may be influenced by ESR1 or PIK3CA status (Abstract GS3-06).
Andrea De Censi, MD, PhD, of Italy’s E.O. Ospedali Galliera, discusses phase III findings showing that low-dose tamoxifen (so-called babytam) given for 3 years still significantly prevents recurrences from noninvasive breast cancer after a median of 7 years from treatment cessation. Babytam at 5 mg/d for 3 years significantly lowered recurrence from noninvasive breast cancer at 10 years without “excess” adverse events (Abstract GS4-08).
Joseph A. Sparano, MD, of the Tisch Cancer Center at Mount Sinai Health System, discusses long-term clinical outcomes data that continue to show many women with early breast cancer can safely forgo chemotherapy, when guided by the 21-gene recurrence score result. The longer follow-up also showed that recurrences of breast cancer continue to occur years after the original diagnosis, although these recurrences were not prevented by chemotherapy use. Racial disparities were not explained by inequities in social determinants of health or treatment adherence, with Black women at higher risk of early recurrence within the first 5 years of diagnosis, but not later recurrence after 5 years (Abstract GS1-05).
Aditya Bardia, MD, MPH, of Massachusetts General Hospital, discusses results from the phase III EMERALD trial, the first study to demonstrate improved progression-free survival vs standard of care in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer with one to two prior lines of endocrine treatment, with or without one line of chemotherapy. This finding applied to all patients in the study, including the subgroup with ESR1 mutations (Abstract GS3-01).
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, discusses results from the POSITIVE trial, which showed that a temporary interruption of endocrine therapy in women with hormone-responsive breast cancer in order to attempt pregnancy, does not affect short-term disease outcomes. The study found that 74% of women had at least one pregnancy, most (70%) within 2 years. Birth defects were low (2%) and were not clearly associated with treatment exposure. Dr. Partridge explains that these data stress the need to incorporate patient-centered reproductive health care in the treatment and follow-up of young women with breast cancer (Abstract GS4-09).