Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04137640 |
Other study ID # |
Shengjing-LCG003 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
July 19, 2021 |
Est. completion date |
May 31, 2026 |
Study information
Verified date |
July 2021 |
Source |
Shengjing Hospital |
Contact |
Xi Gu, M.D. |
Phone |
+86 18940255116 |
Email |
jadegx[@]163.com |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
With the development of neoadjuvant therapy for tumors, neoadjuvant chemotherapy (NAC) has
become one of the most common and effective methods for preoperative systemic treatment of
locally advanced breast cancer (LABC). Although epirubicin combined with cyclophosphamide and
sequential docetaxel has been widely recognized as the first-line NAC for LABC, there are
still some inoperable LABCs that are insensitive to chemotherapy and miss the opportunity of
surgery, especially those with luminal A and low expression of Ki67. Therefore, neoadjuvant
endocrine therapy has important clinical value for such patients. At present, the combination
of aromatase inhibitor drugs and cyclin dependent kinase 4/6 can significantly improve the
prognosis and survival of LABC compared with aromatase inhibitor monotherapy. However,
whether inoperable LABC patients, especially those who are not susceptible to chemotherapy,
can choose the combination of aromatase inhibitor drugs and cyclin dependent kinase 4/6 as
neoadjuvant endocrine therapy to replace NAC remains unclear. Because the main principle of
endocrine therapy is to induce tumor cell cycle arrest, leading to apoptosis of tumor cells,
the effect is slower than that of chemotherapy. In addition, whether endocrine therapy can
replace chemotherapy as a new adjuvant treatment for patients with inoperable LABC to improve
the operability rate has not yet been fully evidenced. Therefore, this trial aims to conduct
the prospective randomized controlled phase IV clinical trial of palbociclib combined with
letrozole versus epirubicin combined with cyclophosphamide and sequential docetaxel as NAC to
prove the efficacy of palbociclib combined with letrozole in postmenopausal estrogen
receptor-positive LABC patients with low Ki67 expression.
Description:
reast cancer is one of the most prevalent malignant tumors in women, accounting for 23% of
all malignant tumors. Approximately 1.3 million people are diagnosed with breast cancer every
year in the world, and approximately 400,000 people die of breast cancer. The overall median
survival time of patients with advanced breast cancer is only 2-3 years, and the 5-year
survival rate is only about 20%. At present, a considerable number of patients are diagnosed
as LABC at the time of initial diagnosis. Because of the wide range of lesions or poor lymph
node status, surgical treatment is very difficult, and even some patients cannot be operated
on.
With the development of neoadjuvant therapy for tumors, NAC has become one of the most common
and effective methods for preoperative systemic treatment of LABC. The 2018 V2 version of the
National Comprehensive Cancer Network guidelines for breast cancer diagnosis clearly states
that preoperative chemotherapy for LABC should be based on an anthracyclines and can be
combined with taxanes, but about 20% of LABC patients are not sensitive to this protocol.
Heller et al. performed NAC with 5-fluorouracil + epirubicin + cyclophosphamide for 6 weeks
in 88 patients with LABC, and the total effective rate was 78%. After 4 weeks of docetaxel
treatment in patients with poor response, approximately 10% of patients are still not
sensitive. In addition, many studies in and outside China have pointed out that the NAC
effect in some estrogen receptor-positive LABC patients, especially postmenopausal luminal A
patients, is worse than that of estrogen receptor negative or Ki67 overexpression patients.
Ring et al. treated 435 cases of breast cancer with NAC of doxorubicin/cyclophosphamide or
cyclophosphamide/methotrexate/fluorouracil. Pathological complete remission rate was 8.1% in
estrogen receptor-positive patients and 21.6% in estrogen receptor negative patients. Similar
results were obtained in NSABP B-27 test, with the ratio of 8.3% and 16.7% respectively.
Simultaneously, Fashing et al. found that the pathological complete remission of patients
with relatively high Ki67 after NAC with anthracyclines combined with taxanes was higher than
that of patients with low Ki67. Many clinical studies in China have also obtained similar
results; that is, the low expression of Ki67 indicates that the effect of NAC in LABC is not
good.
Considering the above situation, some scholars gradually introduce endocrine therapy into the
NAC of postmenopausal estrogen receptor-positive LABC, namely neoadjuvant endocrine therapy.
At present, neoadjuvant endocrine therapy is practical and feasible for breast cancer with
large tumors and positive hormone receptor. Simultaneously, the efficacy of the
third-generation aromatase inhibitors is better than that of tamoxifen. Z1031 clinical trial
of 381 patients with stage II or III postmenopausal estrogen receptor-positive breast cancer
in the United States preliminarily confirmed that the third-generation aromatase inhibitors
are currently the first choice of effective neoadjuvant endocrine therapy for postmenopausal
estrogen receptor-positive breast cancer. However, 30% to 40% of breast cancer patients
receiving endocrine therapy still have disease progression due to drug resistance, which is
very disadvantageous for LABC patients. The emergence of cyclin dependent kinase 4/6
inhibitors has given hope to such patients. In the guidelines for advanced breast cancer,
Cardoso et al. suggested that a first-line treatment with aromatase inhibitors combined with
cyclin dependent kinase 4/6 inhibitors should be preferred. In a phase II randomized
controlled trial to explore the treatment of estrogen receptor-positive and epidermal growth
factor receptor-2-negative advanced breast cancer by combination of palbociclib, a cyclin
dependent kinase 4/6 inhibitor, and letrozole, an aromatase inhibitor, the results found that
the former could significantly prolong progression-free survival of hormone receptor-positive
advanced breast cancer. Therefore, in February 2015, the US Food and Drug Administration
approved the combination of palbociclib and letrozole for first-line treatment of hormone
receptor-positive advanced breast cancer. However, for inoperable LABC patients, especially
those who are not sensitive to chemotherapy, whether the combination of palbociclib and
letrozole can be used as a neoadjuvant endocrine therapy instead of NAC is not clear.
Although there are relatively few controlled studies on neoadjuvant endocrine therapy and
NAC, the existing evidence suggests that the high level of Ki67 in hormone receptor-positive
cases indicates that the effect of chemotherapy is better than that of endocrine therapy, but
the adverse reaction rate of chemotherapy is high, especially for LABC or older and infirm
patients, while neoadjuvant endocrine therapy can achieve similar effect to NAC. Therefore,
the efficacy of palbociclib combined with letrozole as neoadjuvant endocrine therapy is still
worth looking forward to. Because the principle of endocrine therapy is mainly to induce
tumor cell cycle arrest, leading to apoptosis of cancer cells, so the effect is slower than
that of chemotherapy. In addition, whether the efficacy can replace chemotherapy as NAC in
inoperable LABC patients to improve the operability rate has not yet been fully evidenced.
Therefore, this trial aims to conduct the prospective randomized controlled phase IV clinical
trial using palbociclib combined with letrozole versus epirubicin combined with
cyclophosphamide and sequential docetaxel as NAC to prove the efficacy of palbociclib
combined with letrozole in postmenopausal estrogen receptor-positive LABC patients with low
Ki67 expression.