LBA16 - Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial

Background

Dalpiciclib (dalp), a novel CDK4/6 inhibitor, with fulvestrant improved PFS in patients (pts) with HR+/HER2- advanced breast cancer (ABC) progressing after endocrine therapy (ET) in the phase 3, DAWNA-1 trial (Nature Medicine 2021). Here we assessed dalp with ET in the 1^st-line setting.

Methods

DAWNA-2 was a randomized, multicenter, double-blind, phase 3 trial done in 42 centers in China. Pts with untreated HR+/HER2- locally recurrent or metastatic BC, and any menopausal status were randomized 2:1 to receive dalp (150 mg, po, qd, d1-21, q4w) or placebo + letrozole (2.5 mg, po, qd) or anastrozole (1 mg, po, qd). The primary endpoint was PFS per investigator (INV). A prespecified interim analysis was done after 186 (70.5% of total expected) PFS events occurred (Jun 1, 2022), and the corresponding superiority boundary was 1-sided P <0.0076.

Results

456 pts were randomized to dalp + letrozole/anastrozole (N=303) or placebo+ letrozole/anastrozole (N=153). With a median follow-up of 21.7 and 21.4 mo respectively, PFS per INV was significantly improved in the dalp group vs the placebo group (median, 30.6 mo [95% CI 30.6-NR] vs 18.2 mo [16.5-22.5]; HR 0.51 [95% CI 0.38-0.69], 1-sided P <0.0001). PFS benefit with dalp was evident regardless of menopausal status (Table 1). ORR and DoR per INV also favored the dalp group (Table 1). The most frequent grade ≥3 AEs in the dalp group was neutropenia (85.8% [grade 3/4, 64.6%/21.2%] vs 0 in the placebo group) and leukopenia (66.6% [grade 3/4, 65.9%/0.7%] vs 0). SAEs occurred in 11.9% in the dalp group and 6.5% in the placebo group; 4.0% and 2.0% discontinued any treatment due to AEs respectively. Table: LBA16

Efficacy summary

^∗ StratifiedCox proportional hazards model.^† 1-sided stratified Log-rank test. ^‡ Unstratified Cox proportional hazards model. NR=not reached.

Conclusions

Adding dalp to letrozole/anastrozole significantly prolonged PFS in HR+/HER2- ABC, with manageable toxicities. Dalp is the 4^th CDK4/6 inhibitor showing survival benefit with letrozole or anastrozole in untreated HR+/HER2- ABC, or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib and abemaciclib.

Clinical trial identification

NCT03966898.

Editorial acknowledgement

Editorial assistance was provided by Xiuzhi Wu (Hengrui Pharmaceuticals).

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Disclosure

B. Xu: Financial Interests, Personal, Research Grant: Hengrui; Financial Interests, Personal, Advisory Role: Novartis, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Roche, Pfizer. Z. Tong: Financial Interests, Personal, Research Grant: Hengrui, Novartis, Company, Bio-Thera, Eli Lilly. S. Jiang: Financial Interests, Personal, Full or part-time Employment: Hengrui. N. Bayaxi: Financial Interests, Personal, Full or part-time Employment: Hengrui. X. Zhu: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest.