Impact of BMI on CDK4/6 inhibitors efficacy and safety in advanced breast cancer: Results from a propensity score matched study—CAMELIA.

Abstract

1058 Background: Body mass index (BMI) is strongly associated with the development and progression of breast cancer. Despite the widespread use of cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy (ET) in hormone receptor (HR)-positive advanced breast cancer, the effect of BMI on therapeutic outcomes remains poorly understood. Methods: Patients aged ≥18 years with advanced HR-positive breast cancer who received CDK4/6 inhibitors at six hospitals in China were included. 588 patients admitted between December 2016 and December 2024 were evaluated. Patients were categorized into two groups based on BMI: Group 1 (BMI < 25.0 kg/m²) and Group 2 (BMI ≥ 25.0 kg/m²). Propensity score matching with a 3:1 ratio was performed, resulting in 452 patients included in the final analysis. The median follow-up duration was 21.53 months. Progression-free survival (PFS) and overall survival (OS) across BMI categories were compared using Kaplan-Meier (KM) curves and log-rank test. Univariate and multivariate cox regression analyses were performed to assess the impact of baseline clinical factors on PFS. Results: Of 452 patients, 339 (66.7%) were in Group 1, 113 (33.3%) were in Group 2 at baseline. The KM analysis revealed that patients with BMI ≥ 25 kg/m² had a significantly longer PFS compared to those with BMI < 25 kg/m². The median PFS was 16.77 months (95% CI: 12.86–20.67) in Group 1, versus 12.93 months (95% CI: 11.38–14.49) in Group 2 (p = 0.036, HR 0.737, 95% CI: 0.554–0.981). However, no significant difference in OS was observed between the two groups (Group 1: 55.6 months vs. Group 2: not reached, p = 0.949, HR 1.015, 95% CI: 0.637–1.618). Univariate and multivariate cox regression analyses identified BMI, lymph node, liver, bone, and brain metastasis are independent prognostic factors for the entire cohort. Subgroup analyses revealed that BMI ≥25 kg/m² was associated with improved survival in patients aged < 60 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥ 1, with lung metastases, received ≥ 1 line of chemotherapy, and received ≥2 lines of CDK4/6 inhibitors. While Group 1 demonstrated a higher overall response rate (ORR) (30.4% vs. 26.5%, p = 0.476), Group 2 had a higher disease control rate (DCR) (87.0% vs. 91.2%, p = 0.314), though neither reached statistical significance. No significant differences were found in the incidence of grade 3/4 hematologic adverse events (AEs) (36.9% vs. 31.5%, p = 0.460) or non-hematologic AEs (17.1% vs. 14.4%, p = 0.605). Conclusions: In this study, overweight patients (BMI ≥ 25 kg/m²) with metastatic breast cancer may benefit more from CDK4/6 inhibitors. Moreover, similar adverse events were observed across BMI groups. These findings suggest that BMI could serve as a key predictor of CDK4/6 inhibitors treatment response, providing valuable insights for personalized therapeutic strategies in metastatic breast cancer. Characteristics of patients before and after matching according to BMI categories. Unmatched cohort Matched cohort Characteristics BMI<25kg/m 2 (n=448) BMI≥25kg/m 2 (n=140) P SMD BMI<25kg/m 2 (n=339) BMI≥25kg/m 2 (n=113) P SMD Age grope at study entry, No. (%) 0.134 0.152 0.694 0.036 ＜60years 286 (63.8) 79 (56.4) 204 (60.1) 70 (61.9) ≥60years 162 (36.2) 61 (43.6) 135 (39.8) 43 (38.1) ECOG PS 0.064 0.189 0.350 0.078 0 248 (56.4) 52 (37.1) 149 (43.7) 45 (39.8) ≥1 240 (53.6) 88 (62.9) 191 (56.3) 68 (60.2) Stage at diagnosis 0.217 0.124 0.406 0.072 I-III 368 (82.1) 108 (77.1) 279 (82.3) 96 (84.7) IV 80 (17.9) 32 (22.9) 60 (17.7) 17 (15.0) Estrogen receptor status, No. (%) 0.131 0.226 0.434 0.070 1~10% 9 (2.0) 0 (0.0) 0 (0.0) 0 (0.0) 10~50% 37 (8.3) 16 (11.4) 29 (8.6) 12 (10.6) ＞50% 402 (89.7) 124 (88.6) 310 (91.4) 101 (89.4) Progesterone receptor status, No. (%) 0.328 0.150 0.940 0.030 Negative 65 (14.5) 21 (15.0) 55 (16.2) 19 (16.8) 1~20% 121 (27.0) 29 (20.7) 75 (22.1) 26 (23.0) ＞20% 262 (58.5) 90 (64.3) 209 (61.7) 68 (60.2) HER-2 status, No. (%) 0.052 0.204 0.812 0.053 Negative 418 (93.3) 124 (88.6) 311 (91.7) 104 (92.0) Positive 23 (5.1) 9 (6.4) 21 (6.2) 6 (5.3) Unknown 7 (1.6) 7 (5.0) 7 (2.1) 3 (2.7) Ki-67 status, No. (%) 0.138 0.184 0.475 0.097 ＜20 166 (37.1) 46 (32.9) 120 (35.4) 36 (31.9) ≥20 246 (54.9) 75 (53.6) 188 (55.5) 64 (56.6) Unknown 36 (8.0) 19 (13.5) 31 (9.1) 13 (11.5) Resistance to previous endocrine treatment, No. (%) 0.085 0.234 0.924 0.031 Primary resistance 80 (17.9) 27 (19.3) 61 (18.0) 20 (17.7) Secondary resistance 325 (72.5) 90 (64.3) 239 (70.5) 81 (71.7) ET naïve 42 (9.4) 23 (16.4) 39 (11.5) 12 (10.6) non-sensitive 1 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) Bone metastases 0.281 0.107 0.816 0.024 No 181 (40.4) 64 (45.7) 151 (44.5) 49 (44.1) Yes 267 (59.6) 76 (54.3) 188 (55.5) 64 (56.6) Visceral metastases 0.432 0.084 0.310 0.084 No 183 (40.8) 63 (45.0) 146 (43.1) 44 (40.5) Yes 265 (59.2) 77 (55.0) 193 (56.9) 69 (61.1) Previous endocrine therapy lines, No. (%) 0.136 0.198 0.673 0.068 0 206 (46.0) 77 (55.0) 170 (50.1) 59 (52.2) 1 140 (31.2) 40 (28.6) 100 (29.5) 34 (30.1) ≥2 102 (22.8) 23 (16.4) 69 (20.4) 20 (17.7) CDK4/6 inhibitors treatment lines, No. (%) 0.014 0.286 0.696 0.065 1 155 (34.6) 68 (48.6) 140 (41.3) 50 (44.2) 2 90 (20.1) 22 (15.7) 60 (17.7) 20 (17.7) ≥3 203 (45.3) 50 (35.7) 139 (41.0) 43 (38.1) Combination of CDK4/6 inhibitors therapy, No. (%) 0.644 0.070 0.943 0.028 Aromatase inhibitors 270 (60.3) 86 (61.4) 202 (59.6) 68 (60.2) Fulvestrant 172 (38.4) 51 (36.5) 132 (38.9) 43 (38.1) Others 6 (1.3) 3 (2.1) 5 (1.5) 2 (1.8) Disease-free survival, No. (%) 0.417 0.126 0.478 0.092 ≤2years 75 (16.7) 23 (16.4) 54 (15.9) 21 (18.6) >2years 293 (65.4) 85 (60.7) 225 (66.4) 75 (66.4) De novo stage IV 80 (17.9) 32 (22.9) 60 (17.7) 17 (15.0) BMI: body mass index; ECOG: Eastern Cooperative Oncology Group; HER-2: human epidermal growth factor receptor 2; ET: endocrine treatment; CDK4/6: cyclin-dependent kinase 4/6.