The investigational selective estrogen receptor degrader camizestrant was associated with significantly longer progression-free survival for women with advanced estrogen receptor–positive, HER2-negative (ER+/HER2–) breast cancers, 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.

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.

“The results of SERENA-2 support further development of camizestrant in ER-positive breast cancer,” she said.

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.

Promising, but Early

Carlos Artega, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, who was not involved in the study, said the data look promising in comparison with fulvestrant.

“There is a clear suggestion that this might be better,” he said. “[Camizestrant] seems to be better at reducing the titer in plasma of the ESR1 mutation, and there is very strong basic science that supports that.”

He noted that the study numbers were relatively small, however.

Arteaga was speaking at a media briefing held immediately prior to the presentation of the data in an oral abstract session.

Fabrice Andre, MD, from Gustave Roussy in Villejuif, France, the invited discussant for the oral session, noted that, in patients with ESR1 wild type, where fulvestrant shows some efficacy, camizestrant appears to be equally effective, and that the latter agent may be more synergistic with targeted therapies than fulvestrant.

Given high patient dropout rates with currently available SERDs, there is a need for SERDs used in the adjuvant setting that are effective at minimally bioactive doses for patients who are predicted to poorly adherent, Andre said.

The study was funded by AstraZeneca. Oliveira has received personal funding from AstraZeneca, Guardant Health, Roche, Merck Sharp & Dohme, Pfizer, Seagen, iTeos Therapeutics, Eisai, Novartis, Relay Therapeutics, and Gilead. Arteaga is a scientific adviser to AstraZeneca and others, and has received grant support from Pfizer Lilly and Takeda. Andre disclosed fees to his hospital on his behalf from AstraZeneca, Daiichi Sankyo, Sanofi, Pfizer, Lilly, and Roche.

This story originally appeared on MDedge.com, part of the Medscape Professional Network.

Source: Read Full Article