Abstract 217P
Background
There is very limited data on the safety of switching between CDK4/6i in patients with HR+/HER2- ABC after discontinuing CDK4/6i for toxicity.
Methods
This international retrospective study investigated consecutive HR+/HER2- ABC patients treated with CDK4/6i between 2019 and 2023 at two cancer centers, who switched to another CDK4/6i after discontinuing the firstCDK4/6i for unacceptable toxicity without disease progression. Descriptive statistics, Chi-Squared or Fisher’s exact test for contingency tables and factorial ANOVA were applied. The study aimed to assess the safety and feasibility of this approach.
Results
Of 1413 HR+/HER2- ABC patients treated with CDK4/6i, 67 (5%) switched CDK4/6i for toxicity: ribociclib was the 1st CDK4/6i in 38 (57%), palbociclib in 17 (25%) and abemaciclib in 12 (18%). Most frequent adverse events (AE) leading to switch were: hematological in 30% (G2 3%, G3 21%, G4 6%), liver enzymes increase in 24% (G2 1%, G3 18%, G4 4%) and skin toxicity in 15% (G2 9%, G3 6%). Switched CDK4/6i was palbociclib in 34 patients (51%), abemaciclib in 31 (46%) and ribociclib in 2 (3%). The median time for toxicity resolution was 35 (7-150) days. Recurrence of the same toxicity that led to the switch occurred in 20 patients (30%) and was mainly hematologic (22%), while liver AEs accounted for the remaining 8% (all G1-G2). second CDK4/6i was discontinued for toxicity in only 7 patients (10%). AE severity was significantly lower with the second CDK4/6i for neutropenia (p= 0.047), liver toxicity (p= 0.005), and gastrointestinal AEs other than diarrhea (p=0.008). Patients achieving an objective response and those with visceral disease had higher number of AEs (p<0.001 and p=0.043). Table: 217P
| Main AEs leading to discontinuation | 1st CDK4/6i (%) | 2nd CDK4/6i (%) | p | ||||||
| G2 | G3 | G4 | All | G2 | G3 | G4 | All | ||
| Haematological | 2 (3) | 14 (21) | 4 (6) | 20 (30) | - | 2 (3) | - | 2 (3) | 0.662 |
| Hepatic | 1 (1) | 12 (18) | 3 (4) | 16 (24) | - | - | |||
| Skin | 6 (9) | 4 (6) | - | 10 (15) | - | - | |||
| Diarrhea | 3 (4) | 6 (9) | - | 9 (13) | 1 (1) | 2 (3) | - | 3 (4) | 1.000 |
| Main AEs | G1 | G2 | G3-4 | All | G1 | G2 | G3-4 | All | |
| Neutropenia | 1 (1) | 6 (9) | 31 (46) | 38 (57) | 3 (4) | 14 (21) | 21 (31) | 38 (57) | 0.047 |
| Anemia | 16 (24) | 7 (10) | 4 (6) | 27 (40) | 13 (19) | 7 (10) | 3 (4) | 23 (35) | 0.935 |
| Hepatic | 6 (9) | 1 (1) | 15 (22) | 22 (33) | 8 (12) | 4 (6) | 2 (3) | 14 (21) | 0.005 |
| Diarrhea | 2 (3) | 3 (4) | 6 (9) | 11 (16) | 4 (6) | 5 (7) | 4 (6) | 13 (19) | 0.494 |
| Gastrointestinal (not diarrhea) | 2 (3) | 6 (9) | - | 8 (12) | 8 (12) | 1 (1) | - | 9 (13) | 0.008 |
| Treatment duration Median, months | 3 [0-29] | 10 [0-65]* |
*30 patients still on 2ndCDK4/6i.
Conclusions
Switching CKD4/6i after discontinuation for toxicity seems feasible and could represent a pragmatic option to maximize CDK4/6i efficacy and avoid early discontinuation.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A.A. Viansone: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Eisai Europe; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Advisory Role: Seattle Genetics. T. Grinda: Financial Interests, Personal, Other, Travel fees: AstraZeneca, Gilead, Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca, Cancerologie-pratique; Financial Interests, Personal, Funding: Amgen; Financial Interests, Personal, Research Grant: Philippe Foundation. A. Zambelli: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Lilly, Pfizer, AstraZeneca, Seagen, Merck, Daiichi Sankyo Europe GmbH, Exact Sciences; Financial Interests, Personal, Invited Speaker: Gilead Sciences; Financial Interests, Personal, Advisory Board: Gilead Sciences, Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Daiichi Sankyo Europe GmbH, Lilly. A. Santoro: Financial Interests, Personal, Advisory Role: Bristol-Myers-Squibb (BMS), Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, Incyte; Financial Interests, Personal, Speaker’s Bureau: Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, Lilly, Sandoz, Novartis, BMS, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, ArQule. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, AstraZeneca, Gilead, Seagen, MSD, Novartis, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. R. De Sanctis: Financial Interests, Personal, Research Grant: Gilead Sciences; Financial Interests, Personal, Advisory Board: Lilly, Novartis, Istituto Clinico Gentili, Amgen, Eisai, Ipsen. All other authors have declared no conflicts of interest.