Breast cancer is the most frequently diagnosed cancer in female individuals worldwide, followed by colorectal, lung, and cervical cancers. It is also the leading cause of cancer death, followed by lung, colorectal, and cervical cancers [
For most patients with metastatic breast cancer (MBC), the disease is incurable, and the primary treatment goal becomes symptomatic palliation and disease control to maintain or improve quality of life and possibly to extend survival [
Hormone receptor-positive breast cancer is a subtype of breast cancer that expresses estrogen receptors, progesterone receptors, or both. Endocrine therapy is preferred for bone or soft tissue metastasis and minor visceral metastasis [
Vinorelbine is a semi-synthetic third-generation vinca-alkaloid with a modified catharanthine ring. At the molecular level, it acts on the dynamic equilibrium of tubulin in the microtubulin apparatus of the cell [
Vinorelbine is available for clinical use in intravenous (IV) and oral forms. The oral form is made from gelatin capsules [
The NORBREAST-228 phase II study showed that the clinical benefit rate of oral vinorelbine as a mono-therapy was 56%, and the median progression-free survival (PFS) was 8.2 months [
The current study retrospectively reviewed the medical data of 194 Chinese female patients with pretreated MBC who received oral vinorelbine (monotherapy or in combination) at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Shenzhen, China) between February 2017 and January 2021. The median age of the patients included in the study was 49 years (range, 26–85 years).
Eligible patients had the following characteristics: i) ≥18 years of age; ii) had at least one metastatic lesion (non-visceral, visceral or any metastasis); iii) had not received any vinorelbine (oral or IV) therapy previously. If patients had a history of other malignancies within the previous 5 years, abnormal laboratory findings, or severe comorbid illnesses, they were excluded from the current study. Patients were also excluded if they were enrolled in clinical trials that impacted their daily clinical condition.
Demographic and baseline clinical information of patients was described using standard descriptive and analytical methods. PFS was defined as the time from the start of oral vinorelbine treatment to the date of documented disease progression or mortality from any cause. OS was defined as the time from the start of treatment to the date of mortality from any cause or to the most recent date patients were confirmed to be alive. ORR was defined as the proportion of patients who achieved a partial response (PR) or a confirmed complete response (CR). The clinical benefit rate (CBR) was defined as the proportion of evaluable subjects with CR, PR, or stable disease (SD) for ≥24 weeks.
All statistical analyses were completed using SPSS software (IBM Corp., Armonk, NY, USA; version 26.0). PFS and OS were estimated using the Kaplan-Meier method. In addition, the Kaplan-Meier method and log-rank test were used to analyze the univariate discrimination of PFS and OS by demographic data, baseline clinical information, and toxicities. Furthermore, the combined effects of these variables on both PFS and OS were examined in multivariate analysis using the Cox proportional hazards regression model.
A total of 194 patients with MBC received oral vinorelbine (monotherapy or in combination) (NAVELBINE®, PIERRE FABRE MEDICAMENT) at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2017 and January 2021. The baseline patient characteristics are presented in
The most common metastatic site for tumor metastasis was the lymph nodes (n = 168, 86.6%). In the study, 159 patients (82.0%) had regional lymph node metastases, and 156 (80.4%) had distant lymph node metastases. Other metastatic sites included the muscle and soft tissue (69.1%), bone (54.1%), lung (50.0%), liver (45.4%), chest wall (41.2%), brain (29.4%), pleura (23.2%), skin (12.4%), and contralateral breast (7.2%). A total of 115 patients (59.3%) had more than four metastatic sites.
Additionally, 74.2% of patients had previously received anthracycline- or taxane-based neoadjuvant or adjuvant therapy, 31.4% had not been treated previously after metastasis, and 30.4% had been treated with more than three lines of treatment. Furthermore, 69 patients (35.6%) had a disease-free survival (DFS) of >24 months following initial treatment, while 95 (49.0%) had a DFS of ≤24 months.
Characteristic | n (%) |
---|---|
Age, years | |
<50 | 105 (54.1) |
≥50 | 89 (45.9) |
ECOG performance status | |
0–1 | 158 (81.4) |
2 | 28 (14.4) |
Unknown | 8 (4.1) |
Molecular type | |
Hormone receptor-positive breast cancer | 115 (59.3) |
HER2-positive breast cancer | 93 (47.9) |
Triple-negative breast cancer | 27 (13.9) |
Histopathologic grade | |
I–II | 61 (31.4) |
III | 70 (36.1) |
Unknown | 63 (32.5) |
TNM stage | |
I–II | 54 (27.8) |
III | 74 (38.1) |
IV | 42 (21.6) |
Unknown | 24 (12.4) |
Tumor size, cm | |
≤2.0 | 31 (16.0) |
>2.0 | 130 (67.0) |
Unknown | 33 (17.0) |
DFS duration, months | |
≤24 | 95 (49.0) |
>24 | 69 (35.6) |
Unknown | 30 (15.5) |
Lines of treatment, lines | |
1 | 61 (31.4) |
2–3 | 74 (38.1) |
≥4 | 59 (30.4) |
Metastatic sites | |
Lymph node | 168 (86.6) |
Regional lymph node | 159 (82.0) |
Distant lymph node | 156 (80.4) |
Muscle and soft tissue | 134 (69.1) |
Bone | 105 (54.1) |
Lung | 97 (50.0) |
Liver | 88 (45.4) |
Chest wall | 80 (41.2) |
Brain | 57 (29.4) |
Pleura | 45 (23.2) |
Skin | 24 (12.4) |
Contralateral breast | 14 (7.2) |
Number of metastatic sites, n | |
≤4 | 79 (40.7) |
>4 | 115 (59.3) |
Combined treatment | |
HER2-targeted therapy | 85 (43.8) |
Other chemotherapy | 36 (18.6) |
NAC or AC containing A or T | |
Yes | 144 (74.2) |
No | 50 (25.8) |
Note: ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; DFS, disease-free survival; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; A, anthracycline; T, taxane.
With a median follow-up of 17.0 months (range, 1.5–46.8 months) for 194 patients, there were 152 patients finally had progressive disease (PD) and 55 deaths. In the first efficacy evaluation after two cycles of treatment, there were 53 patients achieved PR, 106 patients achieved SD, and 35 patients were PD, no patients reached CR. As demonstrated in
Although the PFS was longer for patients who achieved remission (comprising patients with CR or PR; n = 53) compared with those who did not (n = 141), no statistically significant difference was identified (8.0 months [95% CI, 6.9–9.1 months]
No treatment-associated mortalities occurred. The major adverse events (AEs) for all grades are presented in
Adverse events | Total, n (%) | Grade I or II, n (%) | Grade III or IV, n (%) |
---|---|---|---|
Leukopenia | 142 (73.2) | 88 (45.4) | 54 (27.8) |
Neutropenia | 141 (72.7) | 64 (33.0) | 77 (39.7) |
Anemia | 127 (65.5) | 104 (53.6) | 23 (11.9) |
Thrombocytopenia | 46 (23.7) | 34 (17.5) | 12 (6.2) |
Hepatic dysfunction | 58 (29.9) | 52 (26.8) | 6 (3.1) |
Nausea | 60 (30.9) | 54 (27.8) | 6 (3.1) |
Vomiting | 62 (32.0) | 56 (28.9) | 6 (3.1) |
Diarrhea | 91 (46.9) | 72 (37.1) | 19 (9.8) |
Hand-foot skin reaction | 32 (16.5) | 28 (14.4) | 4 (2.1) |
By univariate analysis, the difference in PFS and OS among patients with different demographic data and baseline clinical information was first assessed using Kaplan-Meier analysis and a log-rank test. As presented in
Progression-free survival | Overall survival | ||||
---|---|---|---|---|---|
Characteristic | Median PFS, months (95% CI) | Median OS, months (95% CI) | |||
Age, years | 0.546 | 0.297 | |||
<50 | 6.3 (4.8–7.9) | NE (NE-NE) | |||
≥50 | 6.0 (4.2–7.8) | NE (NE-NE) | |||
ECOG performance status | 0.001 | <0.001 | |||
0–1 | 7.5 (6.2–8.8) | NE (NE-NE) | |||
2 | 4.0 (2.6–5.4) | 15.0 (9.0–21.0) | |||
Molecular type | 0.087 | 0.047 | |||
Hormone receptor-positive | 5.6 (4.7–6.5) | 36.0 (NE-NE) | |||
Hormone receptor-negative | 8.0 (5.9–10.1) | NE (NE-NE) | |||
Molecular type | 0.304 | 0.004 | |||
HER2-positive | 7.4 (5.7–9.1) | NE (NE-NE) | |||
HER2-negative | 6.0 (5.0–7.0) | 34.0 (24.8–43.2) | |||
Molecular type | 0.428 | 0.605 | |||
TNBC | 6.0 (0.7–11.3) | NE (NE-NE) | |||
Non-TNBC | 6.3 (5.1–7.5) | NE (NE-NE) | |||
Histopathologic grade | 0.338 | 0.848 | |||
I-II | 6.4 (3.9–8.9) | 34.0 (NE-NE) | |||
III | 6.0 (5.0–7.0) | NE (NE-NE) | |||
TNM stage | 0.445/0.649/0.687a | 0.291/0.874/0.555a | |||
I-II | 6.5 (3.9–9.1) | NE (NE-NE) | |||
III | 5.6 (4.4–6.8) | 32.0 (26.0–38.0) | |||
IV | 7.0 (5.1–8.9) | NE (NE-NE) | |||
Tumor size, cm | 0.601 | 0.060 | |||
≤2.0 | 6.0 (4.0–8.0) | 34.0 (20.5–47.5) | |||
>2.0 | 6.2 (4.8–7.6) | NE (NE-NE) | |||
DFS duration, months | 0.322 | 0.461 | |||
≤24 | 6.0 (3.8–8.2) | 36.0 (28.4–43.6) | |||
>24 | 6.0 (4.0–8.0) | NE (NE-NE) | |||
Lines of treatment, lines | 0.109/<0.001/0.042a | 0.196/0.003/0.061a | |||
1 | 9.5 (7.0–12.0) | NE (NE-NE) | |||
2–3 | 6.0 (4.2–7.8) | NE (NE-NE) | |||
≥4 | 4.3 (2.9–5.7) | 32.0 (18.0–46.0) | |||
Lymph node metastasis | 0.769 | 0.836 | |||
Yes | 6.2 (4.9–7.5) | NE (NE-NE) | |||
No | 6.0 (1.5–10.5) | NE (NE-NE) | |||
Muscle and soft tissue metastasis | 0.955 | 0.804 | |||
Yes | 6.3 (5.0–7.6) | NE (NE-NE) | |||
No | 6.0 (1.3–10.7) | 34.0 (NE-NE) | |||
Bone metastasis | 0.311 | 0.121 | |||
Yes | 6.5 (5.1–7.9) | NE (NE-NE) | |||
No | 6.0 (3.7–8.3) | NE (NE-NE) | |||
Lung metastasis | 0.114 | 0.789 | |||
Yes | 6.0 (4.2–7.8) | NE (NE-NE) | |||
No | 7.0 (4.4–9.6) | NE (NE-NE) | |||
Liver metastasis | 0.003 | 0.003 | |||
Yes | 5.4 (4.3–6.5) | 34.0 (22.0–46.0) | |||
No | 7.5 (5.0–10.0) | NE (NE-NE) | |||
Chest wall metastasis | 0.693 | 0.270 | |||
Yes | 6.0 (3.1–8.9) | NE (NE-NE) | |||
No | 6.3 (4.9–7.7) | NE (NE-NE) | |||
Brain metastasis | 0.001 | 0.002 | |||
Yes | 4.7 (3.8–5.6) | 34.0 (17.5–50.5) | |||
No | 8.0 (6.1–9.9) | NE (NE-NE) | |||
Pleura metastasis | 0.066 | 0.608 | |||
Yes | 4.4 (3.4–5.4) | NE (NE-NE) | |||
No | 8.0 (6.2–9.8) | NE (NE-NE) | |||
Skin metastasis | 0.992 | 0.439 | |||
Yes | 7.0 (5.6–8.4) | 28.0 (NE-NE) | |||
No | 6.0 (4.7–7.3) | NE (NE-NE) | |||
Contralateral breast metastasis | 0.163 | 0.075 | |||
Yes | 4.0 (3.4–4.6) | 27.0 (23.1–30.9) | |||
No | 6.5 (5.3–7.7) | NE (NE-NE) | |||
Number of metastatic sites, n | 0.043 | 0.166 | |||
≤4 | 9.0 (5.7–12.3) | NE (NE-NE) | |||
>4 | 6.0 (4.8–7.2) | NE (NE-NE) | |||
Combined with HER2-targeted therapy | 0.202 | 0.017 | |||
Yes | 8.0 (5.8–10.2) | NE (NE-NE) | |||
No | 6.0 (4.8–7.2) | 34.0 (25.5–42.5) | |||
Combined with other chemotherapy | 0.216 | 0.726 | |||
Yes | 6.0 (5.0–7.0) | NE (NE-NE) | |||
No | 6.4 (4.9–8.0) | NE (NE-NE) | |||
NAC or AC containing A or T | 0.255 | 0.336 | |||
Yes | 6.0 (4.6–7.4) | NE (NE-NE) | |||
No | 8.0 (5.5–10.5) | NE (NE-NE) |
Note: CI, confidence interval; TNBC, triple-negative breast cancer; HER2, human epidermal growth factor receptor 2; NE, not evaluated; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; A, anthracycline; T, taxane; a
In addition, a multivariate model containing all these variables was established (
Progression-free survival | Overall survival | ||||
---|---|---|---|---|---|
Variable | HR (95% CI) | HR (95% CI) | |||
Age, years | |||||
<50 |
1.152 (0.765–1.734) | 0.499 | 0.913 (0.463–1.802) | 0.794 | |
ECOG performance status | |||||
0–1 |
0.639 (0.249–1.643) | 0.353 | 0.074 (0.016–0.347) | 0.001 | |
Molecular type | |||||
Hormone receptor-positive |
2.187 (1.224–3.907) | 0.008 | 2.806 (0.867–9.086) | 0.085 | |
HER2-positive |
0.873 (0.380–2.008) | 0.750 | 0.148 (0.017–1.303) | 0.085 | |
TNBC |
2.618 (1.167–5.870) | 0.020 | 4.007 (0.967–16.606) | 0.056 | |
Histopathologic grade | |||||
I-II |
1.030 (0.651–1.631) | 0.899 | 0.910 (0.404–2.050) | 0.819 | |
TNM stage | |||||
I-II |
0.762 (0.368–1.576) | 0.463 | 1.742 (0.378–8.031) | 0.476 | |
I-II |
1.025 (0.519–2.023) | 0.943 | 2.317 (0.560–9.578) | 0.246 | |
Tumor size, cm | |||||
≤2.0 |
1.209 (0.569–2.566) | 0.622 | 2.120 (0.590–7.612) | 0.249 | |
DFS duration, months | |||||
≤24 |
2.054 (0.917–4.604) | 0.080 | 0.806 (0.242–2.690) | 0.726 | |
Lines of treatment, lines | |||||
1 |
0.734 (0.437–1.231) | 0.241 | 0.671 (0.249–1.808) | 0.430 | |
1 |
0.869 (0.552–1.370) | 0.546 | 1.004 (0.476–2.116) | 0.993 | |
Lymph node metastasis | |||||
Yes |
1.509 (0.705–3.231) | 0.290 | 2.760 (0.629–12.110) | 0.178 | |
Muscle and soft tissue metastasis | |||||
Yes |
0.653 (0.350–1.217) | 0.180 | 0.317 (0.086–1.162) | 0.083 | |
Bone metastasis | |||||
Yes |
0.610 (0.368–1.012) | 0.055 | 0.853 (0.361–2.017) | 0.718 | |
Lung metastasis | |||||
Yes |
1.179 (0.807–1.723) | 0.395 | 0.776 (0.390–1.543) | 0.469 | |
Liver metastasis | |||||
Yes |
1.351 (0.894–2.042) | 0.153 | 2.319 (1.067–5.040) | 0.034 | |
Chest wall metastasis | |||||
Yes |
1.083 (0.707–1.660) | 0.713 | 0.732 (0.327–1.640) | 0.448 | |
Brain metastasis | |||||
Yes |
1.859 (1.228–2.816) | 0.003 | 1.760 (0.821–3.777) | 0.146 | |
Pleura metastasis | |||||
Yes |
1.577 (0.998–2.492) | 0.051 | 2.174 (0.958–4.935) | 0.063 | |
Skin metastasis | |||||
Yes |
0.895 (0.491–1.631) | 0.717 | 1.676 (0.633–4.440) | 0.298 | |
Contralateral breast metastasis | |||||
Yes |
1.179 (0.581–2.394) | 0.648 | 1.900 (0.689–5.241) | 0.215 | |
Number of metastatic sites, n | |||||
≤4 |
0.724 (0.384–1.367) | 0.319 | 0.802 (0.225–2.865) | 0.734 | |
Combined HER2-targeted therapy | |||||
Yes |
1.414 (0.559–3.579) | 0.465 | 5.248 (0.538–51.154) | 0.154 | |
Combined other chemotherapy | |||||
Yes |
1.198 (0.756–1.898) | 0.443 | 0.633 (0.274–1.460) | 0.283 | |
NAC or AC contain A or T | |||||
Yes |
1.150 (0.686–1.930) | 0.595 | 1.294 (0.538–3.112) | 0.565 |
Note: CI, confidence interval; TNBC, triple-negative breast cancer; HER2, human epidermal growth factor receptor 2; NE, not evaluated; NAC, neoadjuvant chemotherapy; AC, adjuvant chemotherapy; A, anthracycline; T, taxane.
This study included 194 patients with MBC who received treatment with oral vinorelbine between February 2017 and January 2021 at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. We aimed to evaluate the efficacy and safety of oral vinorelbine. In this study, the median PFS of all 194 patients was 6.2 months (95% CI, 5.0–7.4 months), while the median OS was not evaluated because more than half of the patients were still alive upon assessment. Among the 194 patients eligible for efficacy analysis, the ORR was 27.3% (53/194), and the CBR was 60.8% (118/194). These results indicated that oral vinorelbine had a high efficacy for the treatment of MBC. Blancas I. performed a real-world study on oral vinorelbine in metastatic breast cancer patients [
Some studies have demonstrated the equivalence of oral and IV formulations in pharmacokinetic studies [
Most patients diagnosed with MBC who received oral vinorelbine received anthracycline- or taxane-containing neoadjuvant or adjuvant therapies (74.2%). Oral vinorelbine was mostly prescribed as a treatment for MBC, either as a single-agent chemotherapy (81.4%; including those in combination with other therapies, such as anti-HER2 therapy, endocrine therapy, and anti-angiogenesis therapy, except chemotherapy) or as combined chemotherapy (18.6%). Single-agent and combined chemotherapy did not demonstrate a statistically significant difference in PFS (6.4 months [95% CI, 4.9–8.0 months]
In the overall study population, the median PFS of oral vinorelbine was 6.2 months (95% CI, 5.0–7.4). The median PFS for patients who received oral vinorelbine as first-line chemotherapy was 9.5 months (95% CI, 7.0–12.0), compared with 6.0 months (95% CI, 4.2–7.8) when given two to three lines of chemotherapy and 4.3 months (95% CI, 2.9–5.7) when given four or more lines of chemotherapy. Steger et al. [
No treatment-associated deaths were observed in our study. Most of the AEs were manageable through symptomatic treatment, dose adjustment, or dose interruption. As reported previously, myelosuppression is the most common hematologic toxicity following oral vinorelbine administration [
The current study is a real-world observational study. Like most retrospective and real-world cohort studies, our study has some limitations. The retrospective design and single-center nature of this study may inevitably lead to bias. Additionally, the difference in combination regimens may increase the difference in efficacy and AEs.
The results of the current study demonstrated that oral vinorelbine as single agent or combination chemo-therapy might bring clinical benefits for patients with MBC. Considering its high efficacy, manageable toxicity, ease of administration, and ability to improve quality of life, oral vinorelbine is a good alternative therapy for patients with MBC.
The findings of this single center real-world study in China showed that oral vinorelbine appeared to be efficacious for MBC, with acceptable toxicity, and can be used for the treatment of MBC patients.