Abstract
Purpose
The multicenter, real-world study aims to explore the clinical efficacy of the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) versus fulvestrant (FUL) in Chinese patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
Methods
We retrospectively collected clinicopathological data of cancer patients receiving CDK4/6i from four cancer centers in China. Clinical benefit rate (CBR), objective response rate (ORR), and progression-free survival (PFS) were compared between AI- and FUL-combined therapy.
Results
A total of 315 patients with HR+/HER2- ABC were qualified. 188 (59.7%) patients received AI+CDK4/6i, and 127 (40.3%) patients received FUL+CDK4/6i therapy. In the overall population, the median PFS was 16.8 months versus 14.9 months for AI+CDK4/6i and FUL+CDK4/6i (p=0.34, HR=0.87, 95% CI=0.64–1.17). ORR (19.7% versus 24.4%, p=0.33) and CBR (69.7% versus 77.2%, p=0.16) were comparable between the two treatment regimens. For patients receiving post-first-line (1L) therapy, CBR for FUL+CDK4/6i therapy was 69.1%, which was significantly higher than 52.6% for AI+CDK4/6i therapy (p=0.04). Among ET-resistant subgroups, FUL+CDK4/6i achieved a higher CBR of 70.1% compared with 56.2% for AI+CDK4/6i (p = 0.008). In other subgroups, including patients receiving 1L CDK4/6i, who had a favorable response to ET, with/without liver metastasis at first relapse, the median PFS, ORR, and CBR showed no statistical difference (all p>0.05).
Conclusion
In general, both AI and FUL combinations are effective alternatives, irrespective of the CDK4/6i treatment line, liver metastasis at first relapse, or endocrine sensitivity. Further studies are expected.
Keywords: CDK4/6 inhibitor, HR+/HER2- breast cancer, advanced breast cancer, AI, fulvestrant
Introduction
Breast cancer is one of the most common malignancies among women worldwide, which poses a great threat to women’s health. Based on receptor biomarkers, breast cancer can be categorized into at least four subtypes, including hormone receptor-positive (HR+)/HER2-negative (HER2-), HR+/HER2-positive (HER2+), HR-/HER2+, and triple-negative breast cancer (TNBC).1,2 Among them, the most prevalent molecular subtype is HR+/HER2- breast cancer, accounting for approximately 60% of all breast cancer cases.2,3 Given the positive expression of estrogen receptor (ER) and/or progesterone receptor (PR), this subtype is generally sensitive to endocrine therapy (ET) and has a better prognosis.3–5
Currently, the combination of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and ET has been developed as an optimal first-line (1L) treatment regimen for HR+/HER2- advanced breast cancer (ABC), due to its survival benefit and manageable toxicity.6–9 Among all CDK4/6i categories, the administration of ribociclib or abemaciclib is associated with improved overall survival (OS).10,11 In clinical practice, aromatase inhibitors (AIs) and fulvestrant (FUL) present as the frequently used ET combinations with CDK4/6i.12,13 In a retrospective study, a great percentage of 90% of patients received palbociclib in combination with either AI or FUL.14
In the MONALEESA-2 trial, postmenopausal patients with HR+/HER2- ABC who were treated with ribociclib plus letrozole at 1L setting obtained a median progression-free survival (PFS) of 25.3 months.15 From the numerical perspective, ribociclib combined with FUL regimen as 1L therapy resulted in an improved PFS of 33.6 months in patients with HR+/HER2- ABC from the MONALEESA-3 clinical trial.16 To see, FUL plus CDK4/6i treatment serves as a more effective choice. Nevertheless, in another clinical trial, Chinese patients with HR+/HER2- ABC who received dalpiciclib plus letrozole or anastrozole as 1L therapy had a median PFS of 30.6 months.17 It is similar to the PFS benefits from ribociclib combined with FUL in the MONALEESA-3 trial. However, considering the lack of head-to-head comparisons, which ET combination contributed to better clinical efficacy of CDK4/6i remains controversial. Further exploration is highlighted.
Indeed, conclusions drawn solely from numerical comparisons are unreliable because patient groups differ with respect to age, menopausal status, metastatic burden, and other characteristics. Therefore, we conducted a real-world and multicenter study to compare the clinical efficacy of CDK4/6i plus either AIs or FUL after balancing multiple clinicopathological factors, with the aim of refining the optimal therapeutic choice of ET combinations for CDK4/6i.
Methods
Data Collection
We collected patients’ information from four cancer centers in China from August 2015 and December 2024, including National Cancer Center (NCC), Chinese PLA General Hospital, Peking University Cancer Hospital & Institute and Qinghai University Affiliated Hospital. The information encompassed a wide range of demographic and clinicopathologic characteristics, involving age, menopausal status, histopathology, ER status, PR status, HER2 status, Ki67 index, adjuvant therapy, treatment lines and the corresponding drug response to CDK4/6i, etc.
Patients who met the specified criteria were qualified. (1) Adult women (age> 18 years). (2) Patients who have a positive status of ER or PR, together with a negative status of HER2. ER, PR, and HER2 status were identified by immunohistochemistry (IHC) scores, which were investigated locally at each hospital based on recommendations from the American Society of Clinical Oncology. In particular, HR+ tumors included those with more than 1% ER or PR. HER2- tumors were defined as IHC score and fluorescence in situ hybridization (FISH), which comprised HER2-zero (IHC score 0) and HER2-low (IHC score 1+ or 2+ with negative FISH) tumors. (3) Patients with metastatic or advanced breast cancer. (4) Patients who received CDK4/6i therapy for more than six weeks (the minimum time interval for follow-up). (5) CDK4/6i was administered with the combination of ET, rather than alone.
Drug Efficacy and Subgroup Analysis
Drug efficacy was identified based on three indicators, including clinical benefit rate (CBR), objective response rate (ORR), and progression-free survival (PFS). Treatment response was defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), according to Response Evaluation Criteria in Solid Tumors 1.1. PFS was described as the period from the start of first-line (1L) or post-1L therapy to confirmed progressive disease or death. ORR was the percentage of eligible populations who achieved a CR or PR to specific CDK4/6i. CBR was the proportion of patients who had a CR, PR or SD for greater than 6 months. All the definitions were referred to the published studies.3,18
Patients were divided into two groups according to ET combinations, including AI and FUL subgroups. The AI subgroup included patients who received letrozole, anastrozole, or exemestane in combination with CDK4/6i, whereas the FUL subgroup included patients who received FUL (500 mg, Q4w). Moreover, patients were grouped by CDK4/6i treatment line, metastatic burden, and endocrine sensitivity to further explore the efficacy of AI versus FUL combinations. 1L/Post-1L treatment was defined as the 1L or ≥1L ET in the metastatic setting, irrespective of chemotherapy and endocrine resistance. Endocrine sensitivity was investigated according to the Advanced Breast Cancer Consensus version 4 (ABC4) guidelines.19 Endocrine sensitivity was defined as a recurrence more than 1 year after completion of adjuvant ET. Endocrine resistance was defined as recurrence within 2 years of adjuvant ET, or relapse during adjuvant ET after ≥2 years and less than 1 year after completion of adjuvant ET, or receiving CDK4/6i as post-1L therapy.
Statistical Analysis
We used Fisher’s exact test to compare baseline features between distinct groups. Univariate and multivariate Cox regression analyses were conducted to investigate the correlation between survival outcomes and specific features. The Kaplan-Meier survival analysis was performed to vividly demonstrate prognostic differences, following the same method as previously described in our studies.20 Hazard ratio (HR) and 95% confidential interval (CI) were measured via the Log rank test. Survival analyses were conducted using the survfit function in the Survival package in R. A P-value of less than 0.05 reached significance. A P value of less than 0.01 was considered statistical tendency. All statistical analyses were conducted via SPSS (version 29.0) and R software (version 4.3.2).
Results
Identification of Eligible Patients
Over the course of almost ten years, we collected 535 cancer patients who were treated with CDK4/6i from four cancer hospitals in China. Among them, eight male patients and three non-breast cancer patients were precluded. 123 female patients of breast cancer who had incomplete records of ER or PR or HER2 status were deleted. Furthermore, nine patients with a positive status of HER2 were filtered out. Using metastatic tumors as an inclusion criterion, 42 patients with HR+/HER2- early breast cancer who were treated with adjuvant CDK4/6i therapy were excluded. Out of the 350 patients, eight patients who received CDK4/6i for less than six weeks were excluded due to early discontinuation of medication. Among them, 27 patients who received CDK4/6i plus SERMs or oral progesterone were excluded from subsequent analyses because the sample size was limited, potentially leading to statistical bias. As a result, a total of 315 patients were qualified for the ensuing assessment. The flowchart is shown in Figure 1. Demographic characteristics of eligible patients are presented in Table 1.
Figure 1.
Flowchart of patient selection of the study.
Table 1.
Baseline Characteristics of Eligible Patients with HR+/HER2- ABC Receiving CDK4/6i
| Characteristics | Total (N=315) |
|---|---|
| Age | |
| Mean±SD | 55.8±10.4 |
| Median[min-max] | 55.0[31.00,86.00] |
| Age (years) | |
| ≤ 45 | 62(19.7%) |
| 4660 | 149(47.3%) |
| > 60 | 104(33.0%) |
| Menopausal statusb | |
| Premenopausal | 117(37.1%) |
| Postmenopausal | 198(62.9%) |
| Pathologya | |
| Invasive ductal carcinoma | 257(89.6%) |
| Others | 30(10.5%) |
| Gradea | |
| I | 5(2.4%) |
| II | 161(75.9%) |
| III | 46(21.7%) |
| Positiona | |
| Left | 173(55.3%) |
| Right | 135(43.1%) |
| Bilateral | 5(1.6%) |
| ER status | |
| ER-negative | 8(2.5%) |
| ER-positive | 307(97.5%) |
| PR status | |
| PR-negative | 50(15.9%) |
| PR-positive | 265(84.1%) |
| HER2 status | |
| HER2 zero | 108(34.3%) |
| HER2 low | 207(65.7%) |
| Subtype | |
| ER+/PR- | 50(15.9%) |
| ER-/PR+ | 8(2.5%) |
| ER+/PR+ | 257(81.6%) |
| Ki67 indexa | |
| < 20% | 92(32.7%) |
| ≥20% | 189(67.3%) |
| Surgery | |
| No | 49(15.6%) |
| Yes | 266(84.4%) |
| Adjuvant therapy | |
| Endocrine therapy | 241(76.5%) |
| Radiotherapy | 123(39.1%) |
| Chemotherapy | 235(74.6%) |
| Site of first metastases | |
| Skin | 36(11.4%) |
| Lymph node | 155(49.2%) |
| Lung | 119(37.8%) |
| Liver | 79(25.1%) |
| Bone | 173(54.9%) |
| Brain | 24(7.6%) |
| Treatment line of CDK4/6i | |
| First-line | 169(53.7%) |
| Post first-line | 146(46.4%) |
| Category of CDK4/6i | |
| Palbociclib | 233(74.0%) |
| Ribociclib | 6(1.9%) |
| Dalpiciclib | 34(10.8%) |
| Abemaciclib | 42(13.3%) |
| ET combinations | |
| AIs | 188(59.7%) |
| FUL | 127(40.3%) |
Notes: aCertain information of some patients was missing from local hospitals. bPremenopausal status was defined as age < 45 years regardless of ovarian function or age from 45–55 years with less than 1 year of amenorrhea, together with positive findings on a premenopausal hormone test (estradiol, >110 pg/mL [to convert to picomoles per liter, multiply by 3.671] or follicle-stimulating hormone, <40 mIU/mL [to convert to units per liter, multiply by 1.0]).
Univariate and Multivariate Analyses of Clinicopathological Features and CDK4/6i Efficacy in Patients with HR+/HER2- ABC
Univariate and multivariate analyses were conducted to control the potential bias from the retrospective study. A total of 17 variables were assessed, including treatment line of CDK4/6i (1L versus post 1L), CDK4/6i categories (palbociclib versus ribociclib versus dalpiciclib versus abemaciclib), age (≤45 years versus 46–60 years versus >60 years), menopausal status (premenopausal versus postmenopausal), type (IDC versus others), grade (Grade I versus Grade II versus Grade III), position (Right versus Left), Ki67 index (< 20% versus≥20%), surgery (Yes versus No), adjuvant endocrine therapy (Yes versus No), adjuvant radiotherapy (Yes versus No), adjuvant chemotherapy (Yes versus No), metastases at first relapse [skin (Yes versus No), lymph node (Yes versus No), liver (Yes versus No), bone (Yes versus No), and brain (Yes versus No)]. Results from univariate and multivariable cox analysis showed that treatment line of CDK4/6i (Figure S1, p < 0.0001), and liver metastasis at first relapse (Figure S2, p < 0.0001), were significantly associated with PFS of CDK4/6i (Table S1). Table S2 and Table S3 presented survival outcomes stratified by treatment line of CDK4/6i and liver metastasis at first relapse.
Clinical Efficacy of AI+CDK4/6i versus FUL+CDK4/6i in Patients with HR+/HER2- ABC
Overall Population
As demonstrated in Table 2, 188 (59.7%) patients were administered with AIs plus CDK4/6i treatment, and 127 (40.3%) patients received FUL plus CDK4/6i therapy. In the overall population, 178 patients reached the study point. The median follow-up period was calculated as 20.4 months (95% CI: 17.7–23.0 months). The median PFS for AI + CDK4/6i was 16.8 months (95% CI: 10.1–23.9 months), which was basically similar to 14.7 months (95% CI: 11.4–18.6 months) for FUL + CDK4/6i (p = 0.34, HR = 1.16, 95% CI = 0.86–1.56) (Figure 2). ORR and CBR were comparable between the two treatment regimens. Specifically, ORR was 19.7% versus 24.4% (p =0.33), and CBR was 69.7% versus 77.2% for AI and FUL (p =0.16).
Table 2.
Characteristics and Survival Outcomes of Patients Stratified by ET Combination
| Characteristics | FUL (N=127) | AI (N=188) | Total (N=315) | P value |
|---|---|---|---|---|
| Age (years) | 0.34 | |||
| ≤ 45 | 20(15.7%) | 42(22.3%) | 62(19.7%) | |
| 46–60 | 62(48.8%) | 87(46.3%) | 149(47.3%) | |
| > 60 | 45(35.4%) | 59(31.4%) | 104(33.0%) | |
| Best response | 0.4 | |||
| PD | 14(11.0%) | 29(15.4%) | 43(13.7%) | |
| PR | 31(24.4%) | 37(19.7%) | 68(21.6%) | |
| SD | 82(64.6%) | 122(64.9%) | 204(64.8%) | |
| ORR | 31(24.4%) | 37(19.7%) | 68(21.6%) | 0.33 |
| CBR | 98(77.2%) | 131(69.7%) | 229(72.7%) | 0.16 |
| PFS | ||||
| Events | 76(59.8%) | 102(54.3%) | 178(56.5%) | 0.36 |
| Months (95% CI) | 14.9 (11.4–18.6) | 16.8 (10.1–23.9) | 15.8 (11.8–19.8) | 0.34 |
Figure 2.
Kaplan-Meier survival curve of progression-free survival (PFS) for HR+/HER2- ABC patients receiving AI versus FUL plus CDK4/6i. The green curve represents patients receiving FUL+CDK4/6i, the red curve represents patients receiving AI+CDK4/6i. Median survival, p value, HR and 95% CI are shown.
Patient Population Stratified by Treatment Lines of CDK4/6i
Given the crucial impact of CDK4/6i treatment lines on PFS, we compared PFS benefits between the two treatment regimens in patient subgroups stratified by treatment line (Table S4).
In the 1L setting, 66 events of disease progression have been reported. The combination of AI and CDK4/6i resulted in the median PFS of 43.6 months (95% CI: 24.5–68.8 months), which was numerically longer than 28.3 months (95% CI: 15.0–44.1 months) from FUL combined with CDK4/6i. However, no statistical significance was observed (p = 0.27, HR = 1.33, 95% CI = 0.80–2.20) (Figure 3A). ORR and CBR from FUL+CDK4/6i therapy were observed to be 30.5%, 86.4%, respectively. It was similar to AI+CDK4/6i therapy, for which ORR and CBR were 24.5% and 81.8%, respectively (ORR p = 0.47, CBR p = 0.52).
Figure 3.
Subgroup analyses of PFS for AI+CDK4/6i versus FUL+CDK4/6i in HR+/HER2- ABC patients. The green curve represents patients receiving FUL+CDK4/6i, the red curve represents patients receiving AI+CDK4/6i. (A) Patients receiving 1L-CDK4/6i treatment, (B) patients receiving CDK4/6i as post-1L therapy, (C) patients without liver metastasis at first relapse, (D) patients with liver metastasis at first relapse, (E) patients who were sensitive to endocrine therapy, (F) patients who did not respond to endocrine therapy. Median survival, p value, HR and 95% CI are shown.
In the post-1L setting, 112 patients reached the endpoint. CDK4/6i+AI regimen led to the median PFS of 6.0 months (95% CI: 3.4–10.5 months), while FUL combinations contributed to the median PFS of 10.9 months (95% CI: 9.0–13.2 months) (p = 0.23, HR = 0.79, 95% CI = 0.55–1.16) (Figure 3B). CBR was 69.1% in patients receiving FUL+CDK4/6i therapy, which was significantly higher than 52.6% in those treated with AI+CDK4/6i therapy (p = 0.04). ORR showed no significant difference between the FUL and AI combination strategy (19.1% versus 12.8%, p = 0.33).
Patient Population Stratified by Liver Metastasis at First Relapse
Since liver metastasis at first relapse has been identified to significantly correlate with survival outcomes of CDK4/6i in both univariate and multivariate cox analyses, it is vital to explore PFS of AI versus FUL combinations in subgroups stratified by liver metastasis (Table S5).
For 236 patients who developed other metastases, 110 events have been observed. Patients receiving AI plus CDK4/6i obtained a median PFS of 25.5 months (95% CI: 20.7–32.1 months), which was similar to 24.6 months (95% CI: 11.0–30.4 months) for FUL plus CDK4/6i regimen (p = 0.40, HR = 1.18, 95% CI = 0.80–1.74) (Figure 3C). ORR was generally similar for AI +CDK4/6i and FUL+CDK4/6i treatment (21.8% versus 22.5%, p = 1). A same tendency was observed in CBR (75.5% versus 83.1%, p = 0.19).
For the remaining 79 patients with liver metastasis at first relapse, 68 HR+/HER2- ABC patients reached the endpoint of PFS. AI plus CDK4/6i regimen resulted in a median PFS of 5.2 months (95% CI: 3.9–8.2 months). Patients who were treated with FUL plus CDK4/6i regimen had a median PFS of 9.3 months (95% CI: 6.4–14.0 months). No statistical significance was observed (p = 0.40, HR = 0.81, 95% CI = 0.51–1.31) (Figure 3D). Regarding drug response, patients with liver metastasis who were treated with FUL plus CDK4/6i were inclined to have higher ORR (28.9% versus 12.2%, p = 0.09). CBR displayed no statistical significance for FUL and AI combined therapy (63.2% versus 48.8%, p =0.26).
Patient Population Stratified by Endocrine Sensitivity
In the study, all patients receiving post-1L CDK4/6i developed endocrine resistance. For patients receiving 1L CDK4/6i therapy, ET sensitivity should be determined by DFS and the completion of adjuvant ET, as previously described. In particular, 149 and 166 patients were classified as ET-sensitive and ET-resistant, respectively (Table S6).
A total of 149 patients were classified as ET-sensitive, of whom 55 developed progressive disease. Patients receiving AI + CDK4/6i regimen had a median PFS of 43.6 months (95% CI: 26.2–67.2 months). FUL + CDK4/6i resulted in a median PFS of 28.3 months (95% CI: 17.9–41.2 months). Though the median PFS from AI + CDK4/6i regimen was 15.3 months longer than FUL + CDK4/6i, the discrepancy was not significant (p = 0.49, HR = 1.22, 95% CI = 0.69–2.15) (Figure 3E). ORR (p = 0.44) and CBR (p = 0.48) were comparable for FUL + CDK4/6i and AI + CDK4/6i treatment.
For 166 ET-resistant patients, 123 events have been observed. The median PFS from FUL + CDK4/6i was comparable to AI + CDK4/6i regimen (10.9 months versus 8.7 months, p = 0.46, HR = 0.87, 95% CI = 0.61–1.25) (Figure 3F). Patients receiving FUL + CDK4/6i therapy obtained greater clinical benefits, as compared to those who received AI + CDK4/6i therapy (CBR: 70.1% versus 56.2%, p = 0.008). ORR was similar between FUL + CDK4/6i and AI + CDK4/6i treatment regimen (19.5% versus 13.5%, p = 0.4).
Discussion
The study initially and comprehensively compared the clinical efficacy of CDK4/6i combined with AI versus FUL utilizing large-scale samples from four Chinese centers, including ORR, CBR, and PFS. From a statistical perspective, AI and FUL showed comparable clinical efficacy across CDK4/6i treatment lines, metastatic burden, and drug sensitivity to ET. Our results indicate that both AI and FUL are optional therapeutic options for the combination treatment of CDK4/6i in patients with HR+/HER2- ABC. This was relatively consistent with the results from the PARSIFAL study. It revealed that palbociclib + FUL as 1L therapy resulted in a median PFS of 27.9 months, which was not statistically different from 32.8 months of letrozole + palbociclib.21 However, in a Bayesian network meta-analysis of thirteen randomized controlled trials, PFS and OS from ribociclib + FUL treatment regimen ranked first among patients with HR+/HER2- ABC, compared with other ET combinations of CDK4/6i.12 It suggested that different ET combination strategies potentially contributed to diverse clinical outcomes with CDK4/6i-based therapy.
In the study, AI and FUL combinations showed tendencies toward clinical benefits, especially with respect to numerical strengths. In particular, CDK4/6i combined with FUL yielded greater clinical benefits in patients who received post-1L therapy, as well as in those who did not respond to ET. One of the most important reasons may be that a majority of patients in the post-1L setting had previously received AI therapy prior to CDK4/6i and might have developed drug resistance to AIs. To be elucidated, previous exposure to ET and associated estrogen receptor 1 (ESR1) mutations have an impact on drug resistance to CDK4/6i. ESR1 mutations predominantly occur in patients with HR+ breast cancer who have undergone a period of AI treatment, with a prevalence of approximately 30%.22,23 ESR1 mutations, including D538G and Y537S, have been shown to correlate with drug resistance to ET (mostly AI) and CDK4/6i-based therapy.24–26 One of the potential mechanisms is that ESR1 mutations can modulate the interaction between ERα protein and other oncogenic signaling pathways, including the phosphoinositidol-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways.27,28 Intriguingly, FUL, which inhibits the growth of estrogen-dependent tumors by inducing ER degradation,29 remains effective in patients with ESR1 mutation-mediated endocrine resistance.30,31 This may explain why FUL combinations may result in favorable clinical benefits from post-1L therapy with CDK4/6i. However, the specific condition of ESR1 mutations of most patients in the study is unknown due to missing ESR1 testing and incomplete medical records. Therefore, caution should be exercised when interpreting results from the study.
The study has several limitations. First, owing to its retrospective nature, it may introduce potential biases. To minimize the potential negative effects of bias, we first conducted univariate and multivariate analyses to investigate the impact of multiple clinicopathological factors on the efficacy of CDK4/6i. Furthermore, subgroups were established to compare the efficacy of AI+CDK4/6i versus FUL+CDK4/6i based on potential factors influencing CDK4/6i efficacy. These factors included treatment line of CDK4/6i, liver metastasis at first relapse, and endocrine sensitivity. Second, the analysis did not differentiate among various types of AIs and CDK4/6i. Lack of stratification may have influenced the results. We performed univariate and multivariate analyses to assess the correlation between four commercially available CDK4/6i categories and PFS. Results showed no statistical significance, indicating that all CDK4/6i agents confer PFS benefits for HR+/HER2- ABC. It was consistent with previous studies.32,33 Regarding the stratification of AIs, missing data at the local hospital precluded further subgroup analyses due to the small sample size. Third, certain clinicopathological characteristics were excluded from the analyses due to incomplete medical records, such as TNM stage and ESR1 information.
Conclusion
For patients with HR+/HER2- ABC, treatment line of CDK4/6i and liver metastasis at first relapse are associated with clinical efficacy of CDK4/6i-based therapy. Both AI and FUL presented as an effective alternative when choosing ET combinations of CDK4/6i, irrespective of the treatment line of CDK4/6i, liver metastasis at first relapse, and endocrine sensitivity. Further head-to-head comparisons are anticipated to investigate the efficacy of AI and FUL combinations for CDK4/6i.
Funding Statement
The study was financially supported by the following sources of funding: the Special Research Fund for Central Universities, Peking Union Medical College (grant number: 3332025188); National Natural Science Foundation of China (grant number: 82103010); Cultivation Project of Medical Oncology Key Foundation of Cancer Hospital, Chinese Academy of Medical Sciences (grant number: CICAMS-MOCP2022004), and Noncommunicable Chronic Diseases-National Science and Technology Major Project (grant number: 2023ZD0502200).
Abbreviations
HR, hormone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer; ER, estrogen receptor; PR, progesterone receptor; ET, endocrine therapy; CDK4/6i, cyclin-dependent kinases 4/6 inhibitor; 1L, first-line; ABC, advanced breast cancer; AIs, aromatase inhibitors; FUL, fulvestrant; OS, overall survival; PFS, progression-free survival; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; CBR, clinical benefit rate; ORR, objective response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ABC4, Advanced Breast Cancer Consensus version 4; HR, hazard ratio; CI, confidential interval; IDC, invasive ductal carcinoma; ESR1, estrogen receptor 1; PI3K/AKT, hosphoinositidol-3-kinase/protein kinase B; MAPK: mitogen-activated protein kinase.
Data Sharing Statement
The data analyzed in the current article will be available on reasonable request to the lead corresponding author (Prof. Fei Ma).
Ethics Approval and Consent to Participate
The study was conducted according to institutional guidelines of the Ethics Committee of Cancer Institute and Hospital, Chinese Academy of Medical Science (approve number: 25/427-5373). The privacy and confidential information of patients were properly handled and protected in the process of medical research and publication. All procedures performed in this study were in compliance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. The informed consent was waived due to its retrospective and non-interventional nature.
Disclosure
The authors report no conflicts of interest in this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data analyzed in the current article will be available on reasonable request to the lead corresponding author (Prof. Fei Ma).