Camizestrant extends PFS for postmenopausal women with advanced breast cancer
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SAN ANTONIO — Camizestrant significantly prolonged PFS compared with fulvestrant among postmenopausal women with advanced ER-positive, HER2-negative breast cancer, according to study results.
Camizestrant (AstraZeneca) — a next-generation oral selective estrogen receptor degrader (SERD) — also appeared well-tolerated, findings presented at San Antonio Breast Cancer Symposium showed.
“The results of SERENA-2 showed the potential of camizestrant as the next-generation endocrine therapy and reflect an important step toward a potential new treatment option that could improve on currently available endocrine therapies and optimize outcomes for patients with advanced ER-positive breast cancer,” Mafalda Oliveira, MD, PhD, attending physician in the department of medical oncology at Vall d’Hebron University Hospital and the Breast Cancer Group at Vall d’Hebron Institute of Oncology in Barcelona, Spain, told Healio. “Camizestrant is currently being investigated in combination with CDK4/6 inhibitors in two pivotal trials, SERENA-4 and SERENA-6.”
Background and methods
Hormone receptor-positive, HER2-negative breast cancer often is treated with therapies that inhibit ER activity, including selective ER modulators (SERMs), aromatase inhibitors and SERDs.
However, most tumors eventually develop resistance to available endocrine therapies and commonly acquire a mutation in ESR1.
“Camizestrant has been tested in a phase 1 study across a range of doses and has shown a very good profile of inhibition of the ER pathway,” Oliveira said during a press conference. “We, therefore, decided to assess different doses of the agent compared with standard of care among women with advanced ER-positive, HER2-negative breast cancer who progressed on prior therapy.”
As Healio previously reported, the randomized phase 2 SERENA-2 trial compared camizestrant with fulvestrant for 240 women (median age, 60 years; 94.2% white) with locally advanced or metastatic ER-positive, HER2-negative breast cancer who previously received endocrine therapy for advanced disease.
Researchers randomly assigned 73 patients to fulvestrant. They assigned the other patients to camizestrant at one of two dose levels — 75 mg daily (n = 74) or 150 mg daily (n = 73). Treatment continued until disease progression.
PFS with camizestrant at both dose levels vs. fulvestrant served as the primary endpoint. Secondary endpoints included safety, objective response rate and clinical benefit rate at 24 weeks.
Findings
Researchers reported reductions in risk for disease progression or death of 42% with the 75 mg camizestrant and 33% with the 150 mg.
Results showed median PFS of 7.2 months with 75 mg camizestrant, 7.7 months with 150 mg camizestrant and 3.7 months with fulvestrant.
Among those with ESR1 mutations, researchers observed a 67% reduction in risk for disease progression or death with 75 mg camizestrant and a 45% reduction with 150 mg.
In this group, results showed median PFS of 6.3 months with 75 mg camizestrant, 9.2 months with 150 mg camizestrant and 2.2 months with fulvestrant.
Among patients without detectable ESR1 mutations, researchers reported reductions in risk for disease progression or death of 22% with 75 mg camizestrant and 24% with the 150-mg dose.
“Camizestrant at 75 mg and 150 mg also increased both objective response rates and clinical benefit rate at 24 weeks compared with fulvestrant,” Oliveira said.
Results of additional high-risk subgroup analyses showed improved efficacy with camizestrant.
Among those with lung or liver metastases, researchers observed a decrease in risk for disease progression or death of 57% with the 75 mg dose and 45% with the 150 mg dose. For those previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, researchers observed reductions in risk for progression or death of 51% with the 75 mg dose and 32% with the 150 mg dose.
“We also observed activity of camizestrant vs. fulvestrant among patients with no prior CDK 4/6 inhibitors,” Oliveira said. “The activity among patients with no lung or liver metastases was less clear.”
Researchers reported grade 3 or higher adverse events of 12.2% with the 75 mg dose, 21.9% with the 150 mg dose and 13.7% with fulvestrant.
Investigators acknowledged study limitations, including the small sample size.
"The results of SERENA-2 support the further development of camizestrant in ER-positive breast cancer,” Oliveira said.
Perspective
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Oral SERDs are emerging at a steady drumbeat. For this trial, camizestrant showed clinical benefit at two doses, 75 mg and 150 mg, compared with fulvestrant. Although there was a numerically small improvement at 150 mg compared with 75 mg, both in all-comers as well as in those with ESR1 mutations, the rate of reported adverse events also was higher. As such, in the announced SERENA-4 and SERENA-6 trials, the 75 mg dose will be combined with palbociclib (Ibrance, Pfizer). The SERENA-2 presentation reviewed some subgroup analysis looking at outcomes of visceral metastases but, given the small size of those subgroups, no conclusions should be drawn.
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Oliveira M, et al. Abstract GS3-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022.
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