At the 2022 San Antonio Breast Cancer Symposium, Mafalda Oliviera MD, PhD, Vall d'Hebron University Hospital, Barcelona, Spain, shared results from the SERENA-2 trial, investigating 2 dosing regimens of oral selective estrogen receptor degrader (SERD) camizestrant for ER-positive, HER2-negative, metastatic breast cancer that progressed after previous endocrine therapy, vs fulvestrant.

Results from SERENA-2 found that camizestrant improved progression-free survival in patients at both 75 mg and 150 mg compared with standard-of-care fulvestrant. Dr Oliviera emphasized this benefit was seen across certain subgroups of patients with unmet needs, such as those who progressed on CDK4/6 inhibitors, with visceral metastasis, and with ESR1 mutations. Currently, there are 2 phase 3 studies, SERENA-4 and SERENA-6, that will define the role of camizestrant in this treatment paradigm.

Transcript:

Hi. I'm Mafalda Oliviera. I'm a medical oncologist in the Vall d'Hebron University Hospital in Barcelona. We are here at the 2022 San Antonio Breast Cancer Symposium, where I presented the results of the phase 2 randomized trial, SERENA-2.

SERENA-2 is a trial that compared different doses of an oral selective estrogen receptor degrader (SERD), camizestrant, with standard-of-care fulvestrant in patients with ER-positive, HER2-negative metastatic breast cancer that had progressive disease after prior endocrine therapy. Patients could have received up to one line of endocrine therapy in the metastatic disease, and up to one line of chemotherapy also in the metastatic disease. They were randomized to receive camizestrant at 75 mg, 150 mg, or 300 mg, or the standard-of-care fulvestrant. The randomization was stratified by prior CDK4/6 inhibitor therapy and by the presence of lung or liver metastasis.

The primary endpoint of the trial was progression-free survival (PFS) as assessed by investigator, by RECIST 1.1 criteria. It is important to know that the camizestrant 300 milligram arm was discontinued after 20 patients were enrolled. This had to do with strategic reasons for the company and not with toxicity concerns.

There were 240 patients included in the trial. All were postmenopausal and all had tumors that were ER-positive. 50% of the patients had received prior CDK4/6 inhibitors, and approximately 60% of the patients had lung or liver metastasis. Approximately 40% of the patients included had an ESR1 mutation detected in circulating tumor DNA (ctDNA) prior to study enrollment. 20% of the patients had received prior chemotherapy in the metastatic setting and 66% of them had received prior endocrine therapy in the metastatic setting.

The primary results of SERENA-2 were positive. Camizestrant at both 75 mg and 150 mg improved PFS in comparison to fulvestrant. The hazard ratio for 75 mg of camizestrant compared to fulvestrant was 0.58 with a median PFS of 7.2 months compared to 3.7 months in the fulvestrant arm. The hazard ratio for the camizestrant 150 mg arm compared to fulvestrant was 0.67 with a median PFS of 7.7 months compared to 3.7 months in the fulvestrant arm.

Importantly, camizestrant at both doses also improved PFS in comparison to the standard of care in some subgroups of patients with special unmet medical need. Patients that had progressed on prior CDK4/6 inhibitors, patients with visceral metastasis, those patients with an ESR1 mutation detection in plasma prior to enrollment, and patients with evidence of ER-driven disease. Camizestrant at both doses led to a significant suppression of the variant allele frequency of the ESR1 mutation from cycle 2 day 1 until cycle 7 day 1. This suppression was also apparent with fulvestrant, but to a lesser extent.

An important point is the toxicity profile of this drug. Camizestrant at both doses was extremely well-tolerated. Dose discontinuations, interruptions, and reductions were very infrequent with camizestrant. The most frequent adverse events with camizestrant were photopsia, bradycardia that was in almost 100% of the cases asymptomatic, asthenia, and arthralgia. This is a drug that is taken orally and has a very favorable toxicity profile.

In summary, SERENA-2 met its primary endpoint: camizestrant both at dose of 75 mg and 150 mg is superior to fulvestrant in terms of PFS in the population of patients with ER-positive, HER2-negative metastatic breast cancer with a favorable toxicity profile. Currently, camizestrant is being tested in 2 phase 3 studies, SERENA-4 and SERENA-6, and those results will be important to define the role of this drug in the new treatment scenario for ER-positive breast cancer.

Source:

Oliveira M, Pominchuk D, Nowecki Z, et al. “Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose Phase 2 SERENA-2 trial.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Poster GS3-02