Abstract
Background
Triple‐positive breast cancer (TPBC) is highly invasive and lacks well‐established treatment strategies, especially in patients with advanced stage disease. This study aimed to explore the efficacy of everolimus in patients with metastatic TPBC (mTPBC) in a multicenter real‐world setting.
Methods
A total of 2518 cancer patients who received everolimus‐based therapy were enrolled from three cancer institutes in China from 2014 to 2022. Their clinicopathological characteristics were collected from medical records. The indicators for the efficacy of everolimus were progression‐free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR).
Results
We collected 79 HER2‐enriched patients that were treated with everolimus‐based therapy, 43 of whom were mTPBC. The most commonly used therapeutic combinations was everolimus plus endocrine therapy (18/43, 41.9%). Among all combinations, everolimus plus chemotherapy plus trastuzumab developed the longest PFS of 10.9 months (95% CI: 1.5–20.3). Seventeen patients (32.6%) with mTPBC received everolimus as frontline treatment (1 L/2 L/3 L, FL), and 26 patients (67.4%) as backline treatment (>3 L, BL). Among all the population, the median PFS for everolimus was 4.5 months (range: 3.0–6.0), ORR was 30.2%, and CBR was 48.8%. PFSFL of 10.9 months was significantly longer than 4.0 months for PFSBL (p = 0.003, HR = 0.31, 95% CI: 0.14–0.67). ORRFL was 41.2%, showing no significance compared to ORRBL of 23.1% (one‐sided p = 0.11). CBRFL was observed better of 76.5% versus CBRBL of 46.2% (one‐sided p = 0.026).
Conclusion
Everolimus as frontline treatment achieves clinical benefits for Chinese patients with mTPBC, which may provide some references for the management of Chinese mTPBC patients.
Keywords: everolimus, metastasis, real‐world study, triple positive breast cancer
The study collected 43 patients with metastatic triple‐positive breast cancer (mTPBC) who received everolimus‐based therapy from three cancer institutes in China. Seventeen patients (32.6%) with mTPBC received everolimus as frontline treatment (1 L/2 L/3 L, FL), and 26 patients (67.4%) as backline treatment (>3 L, BL). Among all the population, the median PFS for everolimus was 4.5 months (range 3.0–6.0), ORR was 30.2%, and CBR was 48.8%. PFSFL of 10.9 months was significantly longer than 4.0 months for PFSBL (p = 0.003, HR = 0.31, 95% CI: 0.14–0.67). ORRFL was 41.2%, showing no significance compared to ORRBL of 23.1% (one‐sided p = 0.11). CBRFL was observed better of 76.5% versus CBRBL of 46.2% (one‐sided p = 0.026).
INTRODUCTION
Triple‐positive breast cancer (TPBC) is a distinct type of breast cancer characterized by the positive status of hormone receptors (HR) of estrogen receptor (ER) and progesterone receptor (PgR), together with human epidermal growth factor receptor 2 (HER2) in immunohistochemical (IHC) staining. 1 This subtype constitutes approximately 10% of all breast cancer cases. 2 , 3 TPBC has been classified as an independent biological subtype, with a poorer prognosis compared to HR‐positive (HR+)/HER2‐negative (HER2‐) subtype but a better prognosis than HR‐negative (HR‐)/HER2‐positive (HER2+) subtype. 4 Several studies have consistently shown that TPBC is highly invasive and exhibits increased proliferative activity. 5 , 6 TPBC patients generally present with higher tumor grades, larger tumor sizes, and an elevated risk of lymph node metastases. 5
There have been few studies on patients with TPBC, particularly for those at advanced stage disease. The primary treatment pattern for metastatic TPBC (mTPBC) is the combination of an anti‐HER2 drug and chemotherapy, with or without endocrine therapy (ET). 7 , 8 Currently, some real‐world studies have reported that chemotherapy‐free regimens involving ET plus anti‐HER2 therapy contribute to extended survival. 9 , 10 , 11 There has also been promising evidence suggesting that the combination of cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, could achieve improved prognosis and drug response in the post second‐line treatment. 12 However, mTPBC patients tend to derive less benefit from anti‐HER2 treatment, such as trastuzumab, compared to those with HR‐/HER2+ breast cancer. 13 , 14 The complicated interaction between ER and the intracellular signaling pathways regulated by HER2 might explain this condition. 15 Moreover, mTPBC patients are more likely to develop resistance to ET. 16 Studies have revealed that the upregulation of the growth factor receptor pathway, which includes HER2, epidermal growth factor receptor, and insulin‐like growth factor‐1 receptor, is a mechanism underlying endocrine resistance in mTPBC. 17 These characteristics emphasize the urgent need to develop efficient therapy tailored for patients with TPBC tumors.
Preclinical studies have demonstrated that the mammalian target of rapamycin (mTOR) pathway, which exerts inhibitory effects on both the HER2 and ER pathways, may affect the development of TPBC tumors. 18 We hypothesize that incorporating mTOR inhibitor everolimus into treatment may enhance the survival of mTPBC patients. Whether the addition of everolimus could help mTPBC patients free from chemotherapy, like CDK4/6 inhibitors, is also an important issue. Therefore, we conducted this study to investigate the efficacy of everolimus for mTPBC patients based on real‐world data.
METHODS
Identification of eligible patients and data collection
From January 2014 to November 2022, patient information was collected from three cancer centers in China (National Cancer Center, Chinese PLA General Hospital, Peking University Cancer Hospital and Institute). We used the following criteria to identify patients qualified for inclusion in the study. (1) Female samples. (2) Positive status of ER and PgR and HER2, which were determined by IHC staining according to the guidelines set by the American Society of Clinical Oncology (ASCO). Tumors with more than 1% ER/PgR were categorized as ER/PgR‐positive. HER2‐enriched status refers to IHC score 3+ or fluorescence in situ hybridization amplification. (3) Patients with advanced or histologically proven metastatic breast cancer. (4) Records of medication duration and drug response of everolimus‐combined treatment were available. The collected data included demographic and clinicopathological characteristics such as age, Ki67 index, TNM stage, adjuvant therapy, visceral involvement at first recurrence, treatment patterns and treatment lines.
Survival outcome
Tumor response was retrospectively evaluated as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). It was assessed by computed tomography (CT), magnetic resonance imaging (MRI), and physical examination based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Progression‐free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR) were used as indicators of drug efficacy. PFS was considered the primary endpoint of the study and was defined as the time from starting the medication to confirmed disease progression or death. ORR was calculated as the percentage of patients who achieved a complete response (CR) or partial response (PR) on everolimus. CBR, on the other hand, measured the rate of patients who had a CR, PR, or SD for more than 6 months.
Statistical analysis
The chi‐squared test was used to compare patient characteristics between different groups. We performed Pearson or Kendall correlation analysis to analyze the correlation of different variables. p‐value of correlation analyses was obtained from one‐tailed test. The Kaplan–Meier method was used to generate survival curves. A log‐rank test was used to assess prognostic differences between different groups. Hazard ratio (HR) and 95% confidence interval (95% CI) were obtained via univariate Cox analysis. A p‐value less than 0.05 was considered statistically significant. SPSS software version 22.0 was used for statistical analysis.
RESULTS
Data collection
Between January 2014 and November 2022, a total of 2518 cancer patients who received everolimus were collected from electronic medical records from three cancer centers in China. Taking positive HER2 status into consideration, 79 female breast cancer patients were selected. Among 79 patients, 65 were from the National Cancer Center, nine from Chinese PLA General Hospital, and five from Peking University Cancer Hospital and Institute. All patients had been administered everolimus in an advanced setting. Subsequently, we filtered out 24 patients who did not have double positive ER and PgR status and obtained 55 patients with mTPBC. To better analyze the survival for everolimus, four patients that had severe medical conditions during the period of everolimus therapy, and eight patients with incomplete records of drug use were excluded. Finally, 43 patients qualified for analyses. The flow chart of selection of patients is shown in Figure 1.
FIGURE 1.
Selection of patients in the study.
Baseline characteristics
The overall median age of patients was 52 years, with 76.7% younger than 60 years. All patients in the study developed recurrence during the following period. The majority of patients (72.1%) experienced only one site of metastasis during their first recurrence. The most common site of metastasis was the lung, affecting 41.9% of patients. Nearly all patients received endocrine therapy (97.7%) and chemotherapy (95.4%) in the adjuvant setting. More than half of patients (65.1%) received adjuvant anti‐HER2 therapy prior to everolimus‐based treatment. In terms of first‐line (1 L) treatment regimens, the most commonly used was chemotherapy plus an anti‐HER2 drug (13, 30.2%), followed by chemotherapy alone (11, 25.6%). Considering the limited number of patients receiving everolimus in the 1 L (5, 11.6%), patients who received everolimus in the first‐, second‐ or third‐line were categorized as the frontline treatment (1 L/2 L/3 L, FL) group, patients at more than third‐line were identified as the backline treatment (post‐3 L, BL) group. As a result, 39.5% of patients received everolimus‐based treatment as FL treatment and 60.5% of patients as BL treatment. The baseline characteristics of patients are summarized in Table 1.
TABLE 1.
Baseline characteristics of patients in the study.
| Characteristics | Total (N = 43) |
|---|---|
| Age | |
| Mean ± SD | 51.33 ± 10.50 |
| Median[min‐max] | 52.00 (30.00,75.00) |
| <60 years | 33 (76.7%) |
| ≥60 years | 10 (23.3%) |
| Menopausal status a | |
| Premenopausal | 11 (25.6%) |
| Postmenopausal | 31 (72.1%) |
| Family history | 12 (27.9%) |
| Histology type a | |
| IDC | 25 (58.1%) |
| Mix | 15 (34.9%) |
| Ductal carcinoma in situ | 2 (4.7%) |
| Ki‐67 index a | |
| >14 | 30 (69.8%) |
| ≤14 | 3 (7.0%) |
| Histological grade a | |
| I | 2 (4.7%) |
| II | 21 (50.0%) |
| III | 11 (26.2%) |
| T stage a | |
| Tis | 2 (4.7%) |
| 1 | 13 (30.2%) |
| 2 | 16 (37.2%) |
| 3 | 3 (7.0%) |
| 4 | 1 (2.3%) |
| N stage a | |
| 0 | 9 (20.9%) |
| 1 | 11 (25.6%) |
| 2 | 11 (25.6%) |
| 3 | 5 (11.6%) |
| M stage a | |
| 0 | 38 (90.5%) |
| 1 | 4 (9.5%) |
| Vascular cancer embolus | |
| No | 36 (83.7%) |
| Yes | 7 (16.3%) |
| Sites of first recurrence | |
| Visceral‐only | 14 (32.6%) |
| Bone‐only | 8 (18.6%) |
| Lymph node | 10 (23.3%) |
| Bone | 14 (32.6%) |
| Lung | 18 (41.9%) |
| Liver | 9 (20.9%) |
| Soft tissue | 4 (9.3%) |
| Number of first recurrence | |
| 1 | 31 (72.1%) |
| ≥2 | 12 (27.9%) |
| Neoadjuvant therapy | 8 (18.6%) |
| Surgery a | |
| No surgery | 2 (4.7%) |
| Breast conserving | 2 (4.7%) |
| Modified radical mastectomy | 25 (58.1%) |
| Radical mastectomy | 12 (27.9%) |
| Adjuvant therapy | |
| Endocrine therapy | 42 (97.7%) |
| Chemotherapy | 41 (95.3%) |
| Radiotherapy | 21 (48.8%) |
| Anti‐HER2 therapy | 28 (65.1%) |
| Disease‐free survival (DFS) | |
| DFS <5 years | 33 (76.7%) |
| DFS≥5 years | 10 (23.3%) |
| DFS≥3 years | 19 (44.2%) |
| First‐line treatment b | |
| Chemotherapy‐combined | 29 (67.4%) |
| ET‐combined | 13 (30.2%) |
| Anti‐HER2 drug‐combined | 26 (60.5%) |
| EVE‐combined | 5 (11.6%) |
| Treatment line of everolimus | |
| FL (1 L/2 L/3 L) | 17 (39.5%) |
| BL (≥4 L) | 26 (60.5%) |
Abbreviations: ET, endocrine therapy; EVE, everolimus; TKI, tyrosine kinase inhibitor.
Some histological types and grades, type of surgery, ki67 index, and TNM stage were missing.
First‐line treatment was grouped as combining method. It means if a patient received both chemotherapy and endocrine therapy (ET) in the first‐line treatment, the patient would be counted in both chemotherapy‐combined and ET‐combined groups.
Choices of everolimus‐combined treatment and associated prognosis
The most common therapeutic option for patients was the combination of everolimus and ET (18/43, 41.9%). The choice of endocrine drugs included exemestane, fulvestrant, letrozole and tamoxifen, with exemestane being the most frequently used (10/18, 55.6%). More details are shown in Table S1.
The prognostic differences generated by different drug combinations were investigated. Only one patient received everolimus plus anti‐HER2 therapy (TDM‐1) that had a poor response (the best response was PD) and PFS of 1.1 months. Since the number of patients receiving everolimus plus anti‐HER2 therapy was so small that bias easily developed, it was excluded from subsequent analysis. First, we compared the efficacy of chemotherapy‐combined and ET‐combined treatment, with the exception of multidrug regimens such as everolimus + chemotherapy + HER2 targeted therapy. The median PFS of patients in the chemotherapy group was slightly longer than that in the ET group, but no significance was observed (4.1 months vs 8.2 months, p = 0.14). The results are presented in Figure 2a. Furthermore, we compared the efficacy of the everolimus + chemotherapy + anti‐HER2 drug group with the everolimus + ET+ anti‐HER2 drug group. Patients who received everolimus +chemotherapy+ anti‐HER2 drug had a median PFS of 5.1 months (95% CI: 0–13.0), showing no significance compared with 4.2 months (95% CI: 3.6–4.8) for patients who received everolimus + ET + anti‐HER2 drug (p = 0.9). Censoring regimen of tyrosine kinase inhibitor (TKI) combinations, the median PFS for everolimus + chemotherapy + trastuzumab was estimated as 10.9 months (95% CI: 1.5–20.3), better than 3.7 months for everolimus + ET + trastuzumab (95% CI: 1.3–6.2). However, the difference was also not statistically significant (p = 0.78, Figure 2b).
FIGURE 2.
The correlation between progression‐free survival (PFS) and different everolimus‐combined regimens in patients with metastatic triple‐positive breast cancer (a: chemotherapy vs ET, b: chemotherapy+Anti‐HER2 vs ET+Anti‐HER2, c: chemotherapy vs chemotherapy+Anti‐HER2, d: ET vs ET+Anti‐HER2).
Subsequently, we explored whether adding trastuzumab to chemotherapy or ET could lead to survival benefits. In the chemotherapy group (Figure 2c), we analyzed eight patients who received everolimus + chemotherapy + trastuzumab (10.9 months, 95% CI: 1.5–20.3), and three patients who received everolimus + chemotherapy (8.2 months, 95% CI: 6.8–9.5). In the ET group (Figure 2d), we analyzed 18 patients that were treated with everolimus + ET (4.1 months, 95% CI: 3.9–4.3), and four patients that were treated with everolimus + ET + trastuzumab (3.7 months, 95% CI: 1.3–6.2). However, no statistical difference was observed in both groups, indicating that the addition of anti‐HER2 drug placed minimal impact on survival in the particular setting (chemotherapy: p = 0.48, ET: p = 0.53).
Outcome of everolimus‐based therapy in different treatment lines
Table 2 shows the characteristics and survival of patients in the FL and BL groups. The age distribution of patients in both groups was found to be similar, with about 75% of patients below the age of 60 years (p = 1.0). The median number of treatment lines was four.
TABLE 2.
Characteristics and outcome for everolimus‐based treatment in patients.
| Characteristics | FL (N = 17) | BL (N = 26) | p‐value |
|---|---|---|---|
| Age | 1.0 | ||
| <60 years | 13 (76.5%) | 20 (76.9%) | |
| ≥60 years | 4 (23.5%) | 6 (23.1%) | |
| Everolimus‐combined regimens | 0.37 | ||
| Endocrine therapy | 11 (64.7%) | 14 (53.8%) | |
| Chemotherapy | 5 (29.4%) | 9 (34.6%) | |
| Anti‐HER2 therapy | 4 (23.5%) | 15 (57.7%) | |
| Best response | 0.04 | ||
| PD | 2 (11.8%) | 13 (50.0%) | |
| PR | 7 (41.2%) | 6 (23.1%) | |
| SD | 8 (47.0%) | 7 (26.9%) | |
| PFS | |||
| Events | 17 | 26 | |
| Median (95% CI) | 10.9 (6.1,15.6) | 4.07 (3.5,4.5) | 0.003 |
| PFS >6 months | 11 (64.7%) | 7 (26.9%) | 0.008 |
| PFS > 12 months | 6 (35.3%) | 3 (11.5%) | 0.03 |
| CBR | 13 (76.5%) | 12 (46.2%) | 0.026 |
| ORR | 7 (41.2%) | 6 (23.1%) | 0.11 |
Abbreviations: CI, confidence interval; CBR, clinical benefit rate; ORR, objective response rate; PD, progressive disease; PFS, progression‐free survival; PR, partial response; SD, stable disease.
In the study, everolimus‐based therapy was effective in 30.2% of patients (including CR/PR). The ORR for everolimus was 41.2% in the FL group, showing no significance compared to 23.1% in the BL group (one‐sided p = 0.11). A total of 48.8% of patients derived clinical benefit from everolimus, as measured by CBR, including CR/PR/SD >6 months. A higher percentage of patients in the FL group had a PFS of more than 6 months (64.7% vs. 26.9%, one‐sided p = 0.008), as well as PFS of more than 12 months (35.3% vs. 11.5%, one‐sided p = 0.03). The CBR was observed better of 76.5% in the FL group versus 46.2% in the BL group (one‐sided p = 0.026).
The overall median PFS for everolimus in patients with mTPBC was 4.5 months (95% CI: 3.0–6.0). Subgroup analyses revealed that patients in the FL group had a median PFS of 10.9 months (95% CI: 6.1–15.6), significantly longer in comparison of 4.1 months (95% CI: 3.5–4.5) in the BL group (p = 0.002, HR = 0.4, 95% CI: 0.2–0.7). Patients who received everolimus‐based therapy had a 60% reduction in the risk of progressive diseases (Figure 3).
FIGURE 3.
Survival analysis of patients with metastatic triple‐positive breast cancer receiving everolimus in frontline (FL) treatment and the backline (BL) treatment.
Moreover, we analyzed the association between PFS and other clinicopathological factors. They included age, Ki67 index, TNM stage, DFS, adjuvant therapy, metastatic sites at first recurrence and number of metastatic sites. Only the site of initial metastasis in soft tissues was significantly related to PFS of everolimus in patients with mTPBC (p = 0.03, HR = 3.1, 95% CI: 1.1–9.1). Specifically, patients with metastasis in soft tissues, such as the chest wall or an axillary mass, had a PFS of 1.8 months (95% CI: 1.4–2.2), shorter than 5.1 months (95% CI: 3.7–6.6) in patients with metastasis in other sites (Figure S1). The details of univariate Cox analysis are presented in Table S2 and Figure S2.
DISCUSSION
To the best of our knowledge, this is the first multicenter and real‐world study to exclusively evaluate everolimus‐based regimens in the TPBC population of patients who have developed metastases in Chinese clinical practice.
Everolimus‐based treatment is a choice for patients with HR+ breast cancer in a salvage setting. However, studies designed for patients with mTPBC assessing the efficacy of everolimus are insufficient. In the present study, we first compared the benefit of everolimus combined with different systemic therapies in mTPBC patients. We then explored the efficacy of everolimus in different treatment lines for mTPBC patients using retrospective information from three cancer centers in China.
First, the study examined the survival impact of different everolimus‐combined regimens in patients with mTPBC in a real‐world setting. ET‐combined treatment is the mainstay, with 58.1% of patients using it in routine clinical practice. Among all the combinations, everolimus plus exemestane is the most commonly used regimen. This is mainly because several studies have shown that this regimen is more efficacious in patients with HR+ metastatic breast cancer (MBC). 19 , 20 , 21 , 22 , 23 In the famous BOLERO‐2 study, adding everolimus to exemestane profoundly improved PFS from 7.8 months to 5.6 months in postmenopausal patients with HR+/HER2– MBC who experienced endocrine resistance. 20 Another network meta‐study showed that the combination of everolimus plus exemestane provided better survival compared to both fulvestrant 250 and 500 mg following adjuvant or first‐line endocrine therapy. 22 A previous study even reported that everolimus plus exemestane developed better drug response and PFS than chemotherapy in patients with HR+ MBC. 23 However, PFS benefit was not ideal for such chemotherapy‐sparing regimens in the study. Patients treated with ET plus everolimus had a median PFS of 4.1 months, which was similar to 4.2 months observed in patients receiving ET plus HER2‐targeted plus everolimus. It was inferior to the efficacy in HR+/HER2‐ patients (STEPAUT: 14 months [95% CI: 8.7–31], BRAWO: 10.1 months [95% CI: 6.7–17.6], EVEREXES: 9.3 months [95% CI: 8.7–11.6]). 24 , 25 , 26 This was consistent with other comparative analyses. It further showed that patients with HR+/HER2‐ MBC had a better survival outcome from everolimus‐based treatment compared to patients with HR+/HER2+ MBC. 27 , 28
PFS data for everolimus in patients with mTPBC is deficient, especially for chemotherapy‐free regimens. This prompted us to compare the findings with studies that evaluated chemotherapy‐sparing therapies. In a retrospective single‐center study involving 28 patients with mTPBC, the median PFS for trastuzumab plus fulvestrant regimens was 6.4 months, and the median treatment line was 6. 11 In another phase 3 clinical trial with 385 patients with HR+/HER2+ MBC (single ER+/PgR+ patients were included), PFS for ET plus trastuzumab and ET plus lapatinib was 5.6 and 8.3 months, respectively. 9 The reported data showed better outcomes compared to the study, suggesting that everolimus combined with ET with or without anti‐HER2 drug might not be an optimal combination for mTPBC patients from this perspective.
Furthermore, we explored the efficacy of chemotherapy combined with everolimus (with or without anti‐HER2 treatment) in patients with mTPBC. Patients treated with chemotherapy plus everolimus were observed to have a longer PFS compared to patients with ET plus everolimus, regardless of the addition of anti‐HER2 therapy. Among all chemotherapeutic drugs, vinorelbine was the most commonly used combination (7/14, 50.0%), followed by capecitabine (3/14, 21.4%). Previous studies have reported survival of such combinations in prior treatment lines. In a phase 3 randomized clinical trial, PFS for vinorelbine plus everolimus plus trastuzumab was 7.0 months. This study contained 317 patients with single/double ER+/PR+ and HER2+ MBC who had previously received taxane therapy. 29 In our study, PFS for chemotherapy plus everolimus plus HER2‐targeted therapy was 5.1 months. It was worse than the BOLERO‐3 study. This difference could be attributed to higher expression level of HR in patients with TPBC, which has been shown to decrease the sensitivity of tumor cells to chemotherapy. 4 This may explain why mTPBC patients exhibit poorer survival from chemotherapy compared to HER2+ subtypes.
Intriguingly, PFS for chemotherapy plus everolimus plus trastuzumab in patients with mTPBC was 10.9 months, which is significantly higher than other regimens. It infers that such everolimus combination might be an alternative treatment option for patients with mTPBC. Although previous studies showed favorable efficacy and tolerance of chemotherapy‐free regimens in mTPBC patients, 9 , 11 we could not easily reach a consensus. In other words, patients with mTPBC were not lightly free from chemotherapy when they received everolimus treatment. We subsequently analyzed the characteristics of these patients. Among eight patients analyzed, two patients received chemotherapy plus everolimus plus trastuzumab in the frontline group and six patients in the backline treatment group. Half of patients in the backline treatment group also had a PFS more than 6 months, and were all found to be premenopausal. It indicates that premenopausal patients may derive greater benefits from everolimus‐based treatment, although menopausal status was not significantly correlated with prognosis in the overall population. Studies have revealed that patients with distinct menopausal status have different biological behaviors and molecular landscapes, thus contributing to different drug response and prognosis. 30 , 31 , 32 However, caution should be exercised as several potential factors can affect the reliability of results, such as differences in patient populations, drug dose, treatment lines and limited sample size of the study.
Next, the efficacy of everolimus in different treatment lines in patients with mTPBC was evaluated. Due to limited samples in the study, we allocated patients treated with everolimus in the 1 L/2 L/3 L as a group for analyses to reduce bias of results in single 1 L or 2 L treatment. As a result, mTPBC patients receiving everolimus as frontline treatment had a better prognosis than those receiving backline treatment. This was reflected by an extended PFS and a higher CBR. PFS of 10.9 months in the frontline treatment was in line with findings of two single‐arm studies. For patients with ER+/HER2‐ MBC, 1 L‐PFS for everolimus and exemestane was 10.1 months in one noninterventional study of 3000 patients, 24 and 9.3 months in another multicenter phase 3b study. 25 We then compared PFS data for everolimus in other studies with HR+/HER2+ patients. PFS for frontline treatment was greater than data from a double‐blind clinical trial, which reported PFS for vinorelbine plus everolimus plus trastuzumab≤3 L was 7.0 months. 29 In the famous BOLERO‐1 study, 1 L‐PFS for everolimus plus trastuzumab and paclitaxel was reported as 15.0 months, higher than 10.9 months in the study. 33 However, CBR was comparable with 76.5% in the study versus 75.8% in the BOLERO‐1 study. 33 Everolimus‐based treatment in the frontline could therefore achieve favorable clinical outcomes for patients with TPBC in the salvage setting. Nevertheless, it is challenging to accurately determine combinations with the greatest efficacy given the limited samples in each treatment regimen.
The present study had several limitations. First, the sample size within each subgroup was relatively small, which might have introduced bias. Second, medical records were lacking standardization in earlier years with incomplete clinicopathological information in many hospitals. Therefore, it is crucial to exercise caution when interpreting the findings of this study.
In conclusion, based on multicenter, real‐world clinical information, we first report that everolimus‐based treatment in the frontline achieve clinical benefits in Chinese mTPBC patients and the optimal combination might be chemotherapy plus everolimus plus trastuzumab. The results indicate that everolimus‐based treatment could be an alternative for Chinese mTPBC patients.
AUTHOR CONTRIBUTIONS
Ying Fan and Weihong Zhao supervised the study. Yujing Tan and Hanfang Jiang contributed equally to the study. All authors collected data. Yujing Tan and Xinzhu Tian analyzed data. Yujing Tan conducted formal analyses and wrote the manuscript. Ying Fan, Weihong Zhao, and Hanfang Jiang revised the manuscript. All authors contributed to the article and approved the submitted version.
FUNDING INFORMATION
The project was supported by Major Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS‐MOMP2022003) and Star of Hope Program, Talenet Incentive plan of Cancer Hospital, Chinese Academy of Medical Sciences.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
INFORMED CONSENT STATEMENT
The study was conducetd according to institutional guidelines of the Ethics Committee of Cancer Institute and Hospital, Chinese Academy of Medical Science. The informed consent was waived due to its retrospective and noninterventional nature.
Supporting information
Figure S1. The correlation between progression‐free survival (PFS) and soft tissue metastasis at first recurrence.
Figure S2. The forest plot of Univariant Cox analyses.
Table S1. The proportion of different everolimus‐combined regimens.
Table S2. Univariant Cox analyses of clinicopathological characteristics and PFS.
Tan Y, Jiang H, Ma F, Wang J, Zhang P, Li Q, et al. Efficacy of everolimus‐based therapy in advanced triple‐positive breast cancer: Experience from three cancer centers in China. Thorac Cancer. 2023;14(34):3397–3405. 10.1111/1759-7714.15133
Yujing Tan and Hanfang Jiang are co‐first authors.
Contributor Information
Weihong Zhao, Email: zhaowh0818@163.com.
Ying Fan, Email: fanying@csco.ac.cn.
DATA AVAILABILITY STATEMENT
The data underlying this article will be shared on reasonable request to the corresponding author.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. The correlation between progression‐free survival (PFS) and soft tissue metastasis at first recurrence.
Figure S2. The forest plot of Univariant Cox analyses.
Table S1. The proportion of different everolimus‐combined regimens.
Table S2. Univariant Cox analyses of clinicopathological characteristics and PFS.
Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.