medwireNews: Treatment with the novel oral selective estrogen receptor degrader (SERD) camizestrant significantly improves progression-free survival (PFS) versus fulvestrant in patients with pretreated, estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, shows a phase 2 study.
The PFS benefit was seen with both trialed doses of camizestrant – 75 and 150 mg/day – and across several “prespecified subgroups of unmet medical need,” such as patients with ESR1 mutations, reported Mafalda Oliveira (Vall d’Hebron Institute of Oncology, Barcelona, Spain) at the 2022 San Antonio Breast Cancer Symposium in Texas, USA.
She therefore believes that “the results of SERENA-2 support the further development of camizestrant in ER-positive breast cancer and recruitment to two phase 3 studies of camizestrant in advanced breast cancer – SERENA-4 and SERENA-6 – continues.”
The SERENA-2 researchers enrolled 240 postmenopausal women who had received one prior line of endocrine therapy and one of chemotherapy for advanced disease, and randomly assigned them to receive the oral SERD camizestrant at a daily dose of 75 or 150 mg or intravenous fulvestrant 500 mg. A third camizestrant arm – with a 300 mg/day dose – was closed early due to strategic reasons, explained the presenter.
At a median follow-up of 16.6–17.4 months, camizestrant treatment led to “a statistically significant and clinically meaningful improvement” in the primary endpoint of investigator-assessed PFS compared with fulvestrant, said Oliveira.
The median PFS durations in the camizestrant 75 mg and 150 mg groups were 7.2 and 7.7 months, respectively, versus 3.7 months in the fulvestrant group, giving adjusted hazard ratios (HRs) for progression or death of 0.58 and 0.67, respectively.
Oliveira noted that camizestrant also achieved “clinically meaningful” improvements in PFS relative to fulvestrant in several high-risk subgroups.
For instance, in the 129 patients with lung and/or liver metastases, the median PFS was longer with camizestrant 75 mg and 150 mg than fulvestrant, at 7.2 and 5.6 months versus 2.0 months, respectively. The corresponding HRs were a significant 0.43 and 0.55.
And among the 83 participants who had detectable ESR1 mutations at baseline, PFS was a median of 6.3 months with camizestrant 75 mg, 9.2 months with camizestrant 150 mg, and 2.2 months with fulvestrant, where the differences between the groups was significant. This gave HRs in favor of the oral SERD of 0.33 and 0.55, respectively.
The magnitude of benefit with camizestrant was smaller among the 134 patients without detectable ESR1 mutations, but the HRs still favored camizestrant, at 0.78 for the 75 mg dose and 0.76 for the 150 mg dose, highlighted the investigator.
She moved on to the safety data and reported that treatment-related adverse events (TRAEs) of grade 3 or worse were “infrequent,” occurring in 1.4% of patients given camizestrant 75 mg, 2.7% of those given camizestrant 150 mg, and 1.4% of those treated with fulvestrant. The respective rates of discontinuation due to TRAEs were 2.7%, 0.0%, and 0.0%, and there were no fatal TRAES.
Photopsia was the most common treatment-emergent AE of any grade in the camizestrant arms, occurring at a rate of 12.2% in the 75 mg group and 24.7% in the 150 mg group, but no case was of grade 3 or higher. There were no cases of photopsia with fulvestrant.
In conclusion, Oliveira outlined the key next steps, including longer follow-up and analysis of overall survival as well as “detailed assessments of intersections and interactions between key subgroups” and “analysis of the rich translational dataset.”
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