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The “Pink Killer”-Breast Cancer strong>
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Breast cancer is the most common malignant tumor in women, which seriously threatens women’s health. Many celebrities we know well, such as female singer Yao Beina and Lin Daiyu actor Chen Xiaoxu, all died of breast cancer. In my country, about 300,000 women develop breast cancer every year, and 70,000 die from breast cancer every year[1]. This equates to 1 in 2,500 women developing breast cancer and 1 in 10,000 women dying from breast cancer each year. Although breast cancer has a relatively good prognosis among all cancers, the overall 5-year survival rate in China can reach 72.7% [2], but due to the huge base, it can still be ranked among the causes of cancer death among women in my country To 5th place[1]. ”
Triple Negative Breast Cancer: The End and Dawn
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Three Yin Despair——The sigh of life behind the numbers span>
Breast cancer is a heterogeneous disease that is usually molecularly classified according to the expression of hormone receptors and HER2 receptors on the surface of cancer cells. About 15% to 20% of breast cancers are negative for estrogen receptors, progesterone receptors, and HER2, and are called triple negative breast cancers[3]. Triple-negative breast cancer is easy to metastasize and easy to recur, and it is the most dangerous subtype of breast cancer. Especially with the development of medical technology, the birth of endocrine therapy and HER2 targeted therapy has greatly increased the mortality rate of hormone receptor-positive and HER2-positive breast cancer. However, triple-negative breast cancer with negative hormone receptors and HER2 is not eligible for these new treatments, and chemotherapy is still the main treatment. For example, in the United States, in the 12 years from 2000 to 2012, the mortality rate of both hormone receptor-positive breast cancer and HER2-positive breast cancer decreased by about 50%, The triple-negative breast cancer mortality rate decreased by only 37%, half of which was due to breast cancer screening[4].
Three-yin exploration – limited hope for targeted therapy and immunotherapy strong>
In recent years, some new treatments for triple-negative breast cancer have emerged, such as PARP inhibitors and immunotherapy. These therapies have indeed improved the prognosis of triple-negative breast cancer patients relative to chemotherapy, but their limitations are still relatively large. Like PARP inhibitors, its application requires patients to carry BRCA mutations, and many BRCA-negative patients cannot be used. In patients with BRCA mutations, the median survival time with PARP inhibitors is only about two months longer than chemotherapy, and the patient benefit is limited[5]. The immunotherapy for triple-negative breast cancer also requires patients with CPS≥10[6], the popularity of this test in China is not high, and it also faces the problem that many patients cannot use it. In addition, the immunotherapy drug was withdrawn by the FDA for triple-negative breast cancer indication because the final efficacy data failed to meet the target.[7].
Three Yin Shuguang——Efficacy, Safety, Quality of Life of Goxatuzumab all in Dream
On April 7, 2021, the FDA approved a revolutionary triple-negative breast cancer drug—< /span>Gosatuzumab. This is a new type of antibody-conjugated drug that targets the Trop-2 molecule on the surface of triple-negative breast cancer through the antibody part, and then allows the cytotoxic drugs carried on the antibody to kill the cancer cells. Unlike PARP inhibitors and immunotherapy, which have limited use in triple-negative breast cancer, goxatuzumab targetsThe Trop-2 molecule has a medium-to-high expression rate of about 90% in triple-negative breast cancer, and it can be used in most patients, even without detecting the Trop-2 expression in patients before application. In terms of efficacy, the performance of goxatuzumab is also amazing. In the phase III clinical trial ASCENT, goxatuzumab in patients with advanced triple-negative breast cancer achieved an objective response rate of 35% and a median progression-free survival of 5.6 months. and 12.1 months, which were 7 times, 3 times, and nearly 2 times that of chemotherapy, respectively.[ 8]. A total of 468 patients with refractory or recurrent brain metastases were recruited for this study. Negative breast cancer patients, with a median age of 54 years, were all previously treated with taxanes, most had also been treated with anthracyclines and carboplatin, and 27% had received immunotherapy, but none of these treatments. control their condition. Of these patients, 235 were assigned to receive goxatuzumab and 233 were assigned to receive a single-agent chemotherapy regimen of the physician’s choice. Drugs used in the chemotherapy group included eribulin, vinorelbine, capecitabine, and gemcitabine. After a median follow-up of 17.7 months, the objective response rate in the goxatuzumab group was 35%, and the median progression-free survival was 5.6 months. The median overall survival was 12.1 months. In the chemotherapy group, the objective response rate was only 5%, and the median progression-free survival and median overall survival were 1.7 months and 6.7 months, respectively. Compared with chemotherapy,goxatuzumab reduced the risk of disease progression or death in patients with advanced triple-negative breast cancer 59%, with a 52% lower risk of death.
prolonged triple-negative breast cancer patients without goxatuzumab Progression survivalIn the trial, the incidence of grade 3 adverse reactions in the goxatuzumab group was 45%, and the incidence of grade 4 adverse reactions was 19%, both slightly higher in the chemotherapy group. Common adverse reactions included neutropenia, diarrhea, nausea, alopecia, fatigue, and anemia, and 49% of patients in the goxatuzumab group and 23% of those in the chemotherapy group received growth factor injections for neutropenia. Most of these adverse reactions can be properly managed by symptomatic treatment, dose reduction, and delay of administration. By the end of the trial, 5% of patients in each group had discontinued treatment due to adverse reactions, and 3 patients in each group had died due to adverse reactions. In addition, 22% of patients in the goxatuzumab group and 26% of patients in the chemotherapy group had dose reductions due to adverse reactions. In addition to efficacy and safety, the quality of life of patients is also an indicator that we must be concerned about. The researchers also conducted a questionnaire analysis of the quality of life of patients participating in the ASCENT trial[9]. Quality of life scores were similar in both groups at the start of the trial. As the trial progressed, the quality of life scores in the goxatuzumab group were better than those in the chemotherapy group, both in patients who had remission after treatment and those who did not. Even patients who did not respond to goxatuzumab had better quality of life scores than those who responded to chemotherapy.
goxatuzumab group had better quality of life than chemotherapy group In addition,goxatuzumab was also conducted in the EVER-132-001 trial in Asian patients with triple-negative breast cancer in China, achieving an objective response rate of 38.8%< /strong>[10]. The State Food and Drug Administration also granted priority review of goxatuzumab in May 2020, and it is expected that the drug will soon be approved in China, benefiting domestic triple-negative breast cancer patients.
References:
< p>[1]. Zheng Rongshou, Sun Kexin, Zhang Siwei, et al. Epidemiological analysis of malignant tumors in China in 2015 [J]. Chinese Journal of Oncology, 2019, 41(1):10. p>
[2]. Chen Wanqing, Zheng Rongshou. Incidence, mortality and survival of breast cancer in Chinese women[J]. Chinese Journal of Oncology, 2015, 42(13):668-674. p>
[3]. Waks A G, WinerE P. Breast cancer treatment: a review[J]. Jama, 2019, 321(3): 288-300.
< p>[4]. Plevritis S K, Munoz D, Kurian A W, et al. Association of screening and treatment with breastcancer mortality by molecular subtype in US women, 2000-2012[J]. Jama, 2018,319(2): 154-164.
[5]. Robson M E, TungN, Conte P, et al. OlympiAD final overall survival and tolerability results:Olaparib versus chemotherapy treatment of physician’s choice in patients with agermline BRCA mutation and HER2-negative metastatic breast cancer[J]. Annals ofOncology, 2019, 30(4): 558-566.
[6]. Cortes J, CesconD W, Rugo H S, et al. Pembrolizumab plus chemotherapy versus placebo pluschemotherapy for previously untreated locally recurrent inoperable ormetastatic triple-negative breast cancer (KEYNOTE-355): a randomised,placebo-controlled, double-blind, phase 3 clinical trial[J]. The Lancet, 2020,396(10265): 1817-1828.
[7]. https://www.roche.com/media/releases/med-cor-2021-08-27
[8]. Bardia A, HurvitzS A, Tolaney S M, et al. Sacituzumab govitecan in metastatic triple-negativebreast cancer[J]. New England Journal of Medicine, 2021, 384(16): 1529-1541.
[9]. Loibl S, TolaneyS M, Punie K, et al. Abstract P5-16-01: Assessment of health-related quality oflife by clinical response from the phase 3 ASCENT study in metastatictriple-negative breast cancer (mTNBC)[J]. Cancer Research, 2022,82(4_Supplement): P5-16-01-P5-16-01.
[10]. https://www.everestmedicines.com/News_detail.aspx?nid=431