394P - CDK4/6 inhibitors in metastatic breast cancer: An Italian real-world experience

Background

Abemaciclib, ribociclib and palbociclib are CDK4/6 inhibitors (CDKi) that have shown benefit in combination with endocrine therapy (ET) for estrogen receptor-positive (HR+) metastatic breast cancer (mBC). We aimed to compare the effectiveness of CDKi in mBC using twang propensity weight.

Methods

We performed a retrospective study using data from patients (pts) with HR+/HER2- mBC treated with abemaciclib, ribociclib or palbociclib plus ET in endocrine sensitive and resistant setting between July 2014 and March 2022 in 24 hospitals in Italy with at least 1 year of follow up. We used multinomial propensity weight from the twang package to balance baseline characteristics across treatment groups. We estimated the hazard ratios (HR) for progression-free survival (PFS), overall survival (OS). We also compared the grade 3-4 toxicities between the three drugs.

Results

We included 1184 patients (abemaciclib n=158, ribociclib n=326, palbociclib n=700). After twang propensity weight, the treatment groups were well balanced. In the endocrine-sensitive setting PFS was not significantly different between abemaciclib and ribociclib, while palbociclib was associated with shorter PFS compared both to ribociclib (HR 1.41, 95% CI 1.21-1.66, p<0.001) and abemaciclib (HR 1.33, 1.12-1.58, p=0.001). OS in the palbociclib group was also shorter compared to abemaciclib (HR 1.75, 95% CI 1.35-2.28, p<0.001) and ribociclib (HR1.29, 95% CI 1.05-1.58, p=0.014). In the endocrine-resistant setting abemaciclib showed a longer PFS compared to ribociclib (HR 0.53, 95% CI 0.44-0.64, p<0.001) and albociclib (HR 0.55, 95% CI 0.46-0.66, p<0.001) while no difference was observed between ribociclib and albociclib. OS was not significantly different between the three CDKi. Abemaciclib was associated with higher rates of grade 3-4 diarrhea and thromboembolism, palbociclib with anemia and neutropenia, and ribociclib with liver toxicity (P<0.001).

Conclusions

Our study showed that abemaciclib, ribociclib in the endocrine-sensitive setting have different efficaciesin terms of PFS and OS compared to palbociclib. In the endocrine’resistant setting abemaciclib showed a better PFS compared to other agents. This evidence coupled with different toxicity profiles that may guide treatment selection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Pantano: Financial Interests, Speaker, Consultant, Advisor: Novartis, Gilead, Pfizer, AstraZeneca. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli-Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. R. Caputo: Financial Interests, Speaker, Consultant, Advisor: Lilly, Novartis, Roche, Veracyte, MSD, AstraZeneca, Gilead, Daiichi, Pierre-Fabre. O. Garrone: Financial Interests, Advisory Board: Eisai, MSD, Daiichi Sankyo, Gilead. B. Tagliaferri: Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Speaker, Consultant, Advisor: Novartis, Eli Lilly. A. Toss: Financial Interests, Speaker, Consultant, Advisor: Lilly, Novartis, Pfizer, AstraZeneca, MSD, Daiichi Sankyo, Seagen , Gilead. C. Vernieri: Financial Interests, Advisory Board: Pfizer, Novartis, Eli Lilly, Daiichi Sankyo; Financial Interests, Speaker, Consultant, Advisor: Novartis, Istituto Gentili, Accademia di Medicina, Fenix srl, OVER Group, Eli Lilly; Financial Interests, Research Grant: Roche. P. Vici: Financial Interests, Personal, Advisory Board: Novartis, Eisai, Pfizer, Lilly; Financial Interests, Institutional, Local PI, multicentric trial (Persevera): Roche; Financial Interests, Institutional, Local PI, multicentric study (LIDERA): Roche; Financial Interests, Institutional, Local PI, EPIK B2: Novartis. All other authors have declared no conflicts of interest.