medwireNews: The novel CDK4/6 inhibitor dalpiciclib plus fulvestrant could be “a new treatment option” for patients who have received prior endocrine therapy for hormone receptor (HR)-positive advanced breast cancer, say the DAWNA-1 investigators.
The Chinese phase 3 study not only demonstrated a significant progression-free survival (PFS) advantage with the addition of dalpiciclib (previously known as SHR6390) instead of placebo to fulvestrant, but the benefit “extended beyond initial study treatment,” reported Binghe Xu (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing) at the 2021 ASCO Annual Meeting.
The trial enrolled 361 patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer who had progressed on endocrine therapy and received no more than one previous line of chemotherapy for recurrent or metastatic disease. The median follow-up at data cutoff was around 10.7 months.
Treatment with oral dalpiciclib 150 mg/day for 21 days of each 28-day cycle alongside fulvestrant led to a significant 58% reduction in the investigator-assessed risk for progression or death relative to placebo plus fulvestrant, with respective median PFS durations of 15.7 and 7.2 months.
The findings were similar by independent review, with a significant risk reduction of 55% favoring the CDK4/6 inhibitor, and median PFS times of 13.6 and 7.7 months in the dalpiciclib and placebo groups, respectively.
The objective response rate and clinical benefit rate were higher with dalpiciclib than placebo by investigator assessment, at 27.0% versus 20.0% and 61.0% versus 45.8%, respectively, and this was also the case by independent review, at 30.3% versus 15.8% and 60.2% versus 43.3%, respectively.
Xu also highlighted that the time to first subsequent chemotherapy was significantly prolonged among dalpiciclib- compared with placebo-treated patients, with the median unreached versus 14.2 months, and a hazard ratio of 0.47.
Overall survival data were not mature at the time of analysis.
Grade 3–4 adverse events (AEs) occurred in 88.3% of patients who received dalpiciclib and 11.7% of those given placebo, but the presenter noted that the rates of serious AEs (5.8 vs 6.7%) were comparable between the groups, as were the rates of AE-related treatment discontinuation (2.5 vs 3.3%) and death (0.8 vs 3.3%).
Neutropenia was the most common AE of grade 3 or 4 in the dalpiciclib study arm, reported in 84.2% of participants, followed by leukopenia in 62.1%. By contrast, neither AE occurred at this severity in the placebo arm.
These hematologic toxicities are “consistent with the known class effects of CDK4/6 inhibitors,” Xu pointed out, additionally noting that none of the cases of neutropenia led to discontinuation of dalpiciclib and there were no cases of febrile neutropenia.
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