medwireNews: Dalpiciclib given in combination with an aromatase inhibitor (AI) offers a novel first-line treatment option for patients with locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer, say the DAWNA-2 investigators.
Reporting at the ESMO Congress 2022 in Paris, France, Binghe Xu (Peking Union Medical College, Beijing, China) reported that the CDK4/6 inhibitor achieved the primary endpoint of a significant improvement in progression-free survival (PFS) compared with placebo at the interim analysis of the phase 3 trial conducted in 42 Chinese centers.
“These findings support dalpiciclib plus letrozole or anastrozole as a new first-line treatment option,” he said.
Median PFS per investigator assessment was 30.6 months for the 303 patients randomly assigned to receive dalpiciclib 150 mg for days 1–21 of each 4-week cycle plus letrozole 2.5 mg/day or anastrozole 1.0 mg/day versus 18.2 months for the 153 patients given placebo with either AI, giving a significant hazard ratio (HR) of 0.51 in favor of the CDK4/6 inhibitor.
A similar relationship was also found when PFS was assessed by an independent review committee, with a corresponding median PFS duration of unreached and 22.5 months, and a significant HR of 0.50.
The objective response rate per investigator assessment for patients given the dalpiciclib regimen was 57.4%, the clinical benefit rate was 86.8%, and the median duration of response was unreached; the corresponding values for the control arm were 47.7%, 79.7%, and 15.0 months.
Xu emphasized that the PFS benefit with dalpiciclib versus placebo did not significantly differ between postmenopausal patients and those who were pre- or perimenopausal, with significant HRs of 0.52 and 0.53, respectively.
Safety analysis showed that grade 3 or 4 adverse events (AEs) were frequent with the dalpiciclib regimen, affecting 90.4% of patients versus 12.4% of controls, most commonly grade 3 neutropenia (64.6 vs 0.0%) and leukopenia (65.9 vs 0.0%).
Although AEs resulted in dose reductions in 32.5% of dalpiciclib-treated patients, AEs rarely led to discontinuation (4.0%) and the combination had a “manageable safety profile,” the presenter said.
There were three AE-related deaths with the dalpiciclib regimen and two among controls.
Discussing the abstract at the session, Meritxell Bellet Ezquerra (Vall d’Hebron University Hospital, Barcelona, Spain) said the DAWNA-2 trial findings were “clearly positive,” noting that it is the only phase 3 trial “in endocrine-sensitive disease with [a] mixed pre/peri/post-menopausal population.”
The discussant said that the PFS HRs for both the DAWNA-1 trial of endocrine-resistant disease and the DAWNA-2 trial of endocrine-sensitive tumors are “consistent” with phase 3 trial findings for palbociclib, ribociclib, and abemaciclib in these settings.
She concluded that while the OS data are yet to mature, the PFS results suggest approval for dalpiciclib could be extended to the first-line metastatic breast cancer setting in the Chinese population.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group