SAN ANTONIO – compared with the first-generation SERD fulvestrant Faslodex, in the SERENA-2 trial, shows a study recently presented at the San Antonio Breast Cancer Symposium.
Dr. Mafalda Oliveira
Among 180 postmenopausal women with ER+/HER2– breast cancers that had recurred or progressed following at least one line of endocrine therapy, the median progression-free survival (PFS) after a median follow-up of 16.6-17.4 months was 7.2 months for patients treated at a 75-mg dose of camizestrant and 7.7 months for those treated at a 150-mg dose, compared with 3.7 months for patients who received fulvestrant, reported Mafalda Oliveira, MD, PhD, from Vall d’Hebron University Hospital in Barcelona.
Dr. Mafalda Oliveira
Oral agent
Camizestrant is a next-generation oral SERD and pure estrogen receptor antagonist that was shown in the SERENA-1 trial to be safe and to have clinical activity against ER+ breast cancers.
SERENA-2 pitted camizestrant at doses of 75 mg, 150 mg, or 300 mg against standard-dose fulvestrant, although the 300-mg dose was dropped in a protocol amendment after 20 patients had been assigned to that arm. (Currently planned studies with camizestrant will be conducted with the 75-mg dose.)
The investigators enrolled women with ER+/HER2– advanced breast cancer who had not previously received fulvestrant or an oral SERD. Eligible patients were limited to no more than one prior line of endocrine and one prior line of chemotherapy for advanced breast cancers. The study included patients with both measurable and unmeasurable disease.
The median patient age was about 60 years. Approximately 59% of patients in each arm had either lung or liver metastases. Patients with recurrence in bone only comprised 14.9%-19.4%.
Mutations in ESR1, a gene associated with hormonal resistance, were detectable in 29.7%-47.9% of patients.
Better PFS
As noted before, the primary endpoint of investigator-assessed median PFS favored camizestrant in both the 75-mg arm (7.2 months) and the 150-mg arm (7.7 months), with respective adjusted hazard ratios for progression versus fulvestrant of 0.58 (P = .0124) and 0.67 (P = .0161).
Camizestrant at the 75-mg dose was also superior to fulvestrant among patients who had previously received a cyclin-dependent kinase 4/6 inhibitor, with median PFS of 5.5 months and 3.8 months for the 75-mg and 150-mg doses, respectively, compared with 2.1 months.
The adjusted HR for progression with camizestrant with the 75-mg dose was 0.49, with a 90% confidence interval indicating significance. The 150-mg dose was not significantly superior to fulvestrant, however.
Both camizestrant doses were also superior for prolonging PFS versus fulvestrant among patients with lung and/or liver metastases, with median PFS of 7.2 months, 5.6 months, and 2.0 months, respectively.
The experimental SERD also outperformed fulvestrant in an analysis looking at PFS by ESR1 mutational status and ER-driven disease. Among patients with ESR1 wild type, however, median PFS rates with camizestrant 75 mg and fulvestrant were the same (7.2 months).
The 24-week objective response rates were 15.7% in the 75-mg camizestrant arm, 20% in the 150-mg arm, and 11.8% in the fulvestrant arm. The respective clinical benefit rates, including all patients with responses or stable disease, were 47.3%, 49.3%, and 38.4%. The camizestrant clinical benefit rates did not differ significantly from those with fulvestrant, however.
Treatment-related adverse events of grade 3 or greater occurred in only five patients, and only two patients, both in the 75-mg camizestrant arm, discontinued therapy because of adverse events. There were no treatment-related deaths.
Adverse events that occurred only with camizestrant included photopsia (flashing lights or floaters in the field of vision) and sinus bradycardia.