ASCO: a summary of the latest research progress of three negative breast cancer (TNBC) targeting drugs

The expression of estrogen receptor (ER), progesterone receptor (PR) and proto oncogene human epidermal growth factor receptor (HER2) was negative, accounting for 15% - 20% of all breast cancer typesThe clinical manifestations of TNBC are more invasive, including high recurrence rate, drug resistance to chemotherapy, frequent distal metastasis and poor prognosis< br / > < br / > < br / > (picture source: Baidu picture) < br / > < br / > at present, the most effective chemotherapy combinations for early TNBC include anthracyclines, taxanes and / or platinum drugs, while the neoadjuvant chemotherapy mode (NAC) also provides important prognostic information for clinical pathological complete remission (PCR), and is regarded as an alternative endpoint in many clinical trials (especially TNBC)Compared with patients with PCR, patients with residual invasive disease after neoadjuvant chemotherapy have higher risk of early recurrence and worse prognosis< br / >< br / > < br / > < br / > (picture source: Baidu picture) < br / > < br / > previous studies have shown that capecitabine can be used for adjuvant treatment of residual cancerIn the create-x clinical trial, capecitabine adjuvant treatment can improve the 5-year disease-free survival rate of TNBC patients< br / > < br / > a recent study by Wang Xi's team from cancer prevention and treatment center of Sun Yat sen University found that capecitabine can significantly improve the disease-free survival rate of patients with operable triple negative breast cancer< br / > < br / > a total of 434 patients with operable TNBC were randomly divided into two groups: capecitabine group (n = 221) and observation group (n = 213)The experimental group was treated with capecitabine (650mg / m2, twice a day, one year in a row)The median follow-up time of 56.5 months showed that the 5-year disease-free survival rate (DFS) of capecitabine group was significantly higher than that of the observation group (83% vs73%, P = 0.027)The 5-year distant disease free survival rate (DDFS) was also significantly higher in the observation group (85% vs76%, P = 0.016)However, there was no significant difference in 5-year overall survival (OS) between the two groups (85% vs81%, P = 0.203)202 patients (91.4%) completed capecitabine treatment for one year as planned This study also showed that capecitabine maintenance therapy is a safe and well tolerated treatment strategy, which can significantly improve the disease-free survival rate of operable triple negative breast cancer patients < br / > < br / > Korea University of Korea School of medicine also published a phase II clinical trial, which aims to evaluate the efficacy and safety of triple negative breast cancer (TNBC) patients with residual invasive cancer after the new adjuvant treatment after the combination of atjudanab (an anti-PD-L1 antibody) and capecitabine as well as capecitabine The trial will recruit 284 patients from 15 regions in South Korea, with the main goal of achieving 5-year noninvasive disease survival (IDFs) Secondary goals included 5-year IDFs, distant recurrence free survival (DRFS), overall survival (OS), and medication safety in PD-L1 positive subjects The researchers set up the relevant adoption and exclusion criteria for the recruits At present, the study has recruited 13 patients The previous clinical studies showed that TNBC cell lines and mouse models were more sensitive to PARP1 inhibitors, which provided a strong basis for the development of new therapy for TNBC Olaparib, as a PARP inhibitor, has been approved for clinical treatment of BRCA1 / 2 mutation and HER2 negative metastatic breast cancer < br / > < br / > the Curie Institute in Paris, France, carried out a phase I clinical study of combination of olaparine and radiotherapy (RT) The subjects were patients with inflammatory reaction, local advanced or metastatic triple negative breast cancer (TNBC) or patients with residual cancer after operation < br / > < br / > the purpose of this study was to investigate the maximum tolerated dose (MTD) and to assess dose limited toxicity (DLT) in combination with local radiotherapy < br / > < br / > the results showed that the maximum tolerable dose of olapani could be increased to the target dose of 200 mgx2 without dose limiting toxicity, while the late toxicity study of patients needed further follow-up < br / > < br / > < br / > < br / > recruited patients are divided into two cohorts: one is the cohort of patients with genetic mutations of DDR pathway gene except BRCA1 / 2, and the other is the cohort of patients with somatic mutations of DDR pathway gene including BRCA1 / 2 From March 2018 to January 2020, researchers recruited 53 patients who met the requirements, with the median age of 59 years (covering the range of 30-87 years) The recruited patients were treated twice daily with 300 mg of olapani until the disease worsened or the drug dose toxicity occurred < br / > < br / > < br / > < br / > Olapani, as a PARP inhibitor, has been proved to be effective in BRCA1 / 2 mutation and HER2 negative metastatic breast cancer The aim of this study was to test the antitumor activity of sildenab combined with olapani in patients with metastatic triple negative breast cancer (TNBC) < br / > The recruited patients were given 30 mg sildenab once a day and 200 mg olapamil twice a day until the disease worsened or the dose toxicity appeared The results showed that the overall objective remission rate was 14%, the median remission time was 2 months, the disease control rate was 81%, and the incidence of grade 3 / 4 AES was 66% Hypertension (24%), dyspnea (11%), diarrhea (8%) and vomiting (8%) occurred in 5% of the patients The study showed that the combination of sildenab and olapani had a potential remission effect on 14% of patients with metastatic TNBC The researchers also proposed that timely use of antihypertensive drugs at the beginning of the treatment can effectively control the occurrence of adverse events < br / > < br / > < br / > Table 3: relevant information of patients < br / > < br / > at present, the most promising first-line treatment strategy for local recurrence, inoperable TNBC or metastatic TNBC (mtnbc) is the combination of immunotherapy and chemotherapy < br / > < br / > however, the formulation of an effective and tolerable maintenance program for mtnbc remains to be explored in view of the potential chemical toxicity or drug resistance that may be produced by the maintenance therapy after induction therapy and long-term chemotherapy < br / > < br / > The Helen Diller family comprehensive cancer center at the University of California San Francisco Medical Center has developed a phase II / III open clinical study to explore the efficacy of the combined treatment strategy < br / > After induction treatment, the patients will be divided into two groups The experimental group will receive 200 mg of pamumab every three weeks and 300 mg of olapamil twice a day The control group will continue to use the induction treatment before The treatment will continue until the disease worsens or the drug dose toxicity occurs < br / > < br / > to sum up, with more and more research on the molecular mechanism of triple negative breast cancer, both the adjuvant therapy of capecitabine, the single drug therapy of olapamil and the combination therapy of other drugs provide meaningful research results and references for the treatment of triple negative breast cancer In addition to PARP inhibitors such as olapamil, HDAC inhibitors, platinum drugs, permumab and new adjuvant therapy are more and more used in the treatment of triple negative breast cancer patients Therefore, the treatment and prognosis of triple negative breast cancer will be improved gradually < br / >, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Randomized, phase II trial to evaluate the efficacy and safety of atezolizumab plus capecitabine adjuvant therapy compared to capecitabine monotherapy for triple receptor-negative breast cancer (TNBC) with residual invasive cancer after neoadjuvant chemotherapy (MIRINAE trial, KCSGBR18- 21) First Author: In Hae Park, Division of Hemato-Oncology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul, South Korea 3 Radioparp: A phase I of olaparib with radiation therapy (RT) in patients with inflammatory, locoregionally advanced or metastatic triple-negative breast cancer (TNBC) or patient with operated TNBC with residual disease— Preliminary results First Author: Youlia M Kirova, Institut Curie, Paris, France 4 TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded) First Author: Nadine M Tung, Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute, Boston, MA 5 Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors First Author: Navid Hafez, Yale University School of Medicine, New Haven, CT 6 KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) plus olaparib vs pembro plus chemotherapy after induction with first-line pembro plus chemothera