217P Switching cyclin-dependent kinase inhibitors (CDK4/6i) in patients with hormone receptor-positive (HR+)/human epidermal growth factor-negative (HER2-) advanced breast cancer (ABC) who experienced unacceptable toxicity

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. 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. 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: 217PMain AEs leading to discontinuation1st CDK4/6i (%)2nd CDK4/6i (%)pG2G3G4AllG2G3G4AllHaematological2 (3)14 (21)4 (6)20 (30)-2 (3)-2 (3)0.662Hepatic1 (1)12 (18)3 (4)16 (24)--Skin6 (9)4 (6)-10 (15)--Diarrhea3 (4)6 (9)-9 (13)1 (1)2 (3)-3 (4)1.000Main AEsG1G2G3-4AllG1G2G3-4AllNeutropenia1 (1)6 (9)31 (46)38 (57)3 (4)14 (21)21 (31)38 (57)0.047Anemia16 (24)7 (10)4 (6)27 (40)13 (19)7 (10)3 (4)23 (35)0.935Hepatic6 (9)1 (1)15 (22)22 (33)8 (12)4 (6)2 (3)14 (21)0.005Diarrhea2 (3)3 (4)6 (9)11 (16)4 (6)5 (7)4 (6)13 (19)0.494Gastrointestinal (not diarrhea)2 (3)6 (9)-8 (12)8 (12)1 (1)-9 (13)0.008Treatment duration Median, months3 0-2910 0-65**30 patients still on 2ndCDK4/6i. Open table in a new tab *30 patients still on 2ndCDK4/6i. Switching CKD4/6i after discontinuation for toxicity seems feasible and could represent a pragmatic option to maximize CDK4/6i efficacy and avoid early discontinuation.