Today (June 10, 2022) the official website of the State Food and Drug Administration (NMPA) of China has announced that the marketing application of gosartolizumab for injection has been approved.
According to previously published information, the approved indications are: treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received at least two systematic treatments( at least one of which is for metastatic disease).
Gosartozumab is the world's first antibody-conjugated drug (ADC) to target TROP-2 and significantly improves progression-free and overall survival compared with standard therapy in the treatment of patients with triple-negative breast cancer.
(Screenshot source: NMPA official website)
What is the sanctity of gosavolizumab?
Antibody-drug conjugate (ADC) is a new type of targeted drug composed of monoclonal antibodies (monoclonal antibodies), cytotoxic drugs and connecting agents between the two, which uses the targeting of antibodies to selectively deliver cytotoxic molecules to tumor cells, while exerting anti-cancer effects, to avoid affecting healthy cells. In simple terms, the advantages of ADCs are better anti-tumor effects and fewer adverse reactions.
Sacituzumab govitecan is an ADC that targets TROP-2 with a topoisomerase 1 inhibitor.
TROP-2, also known as human trophoblast cell-surface antigen 2, is a protein that is overexpressed in many epithelial cancers, where high expression is associated with low survival and recurrence of cancer.
Gosartozumab is able to deliver the active metabolite (SN-38) of the chemotherapy drug irinotecan to the interior of cancer cells by binding to the TROP-2 protein. Such a strong combination, the anti-cancer effect has the amazing effect of "1 + 1>2".
SN-38 is a cancer drug that blocks an enzyme called topoisomerase I, which is involved in DNA synthesis in replicating cells, and by blocking this enzyme, it prevents cancer cells from multiplying and eventually dying.
In addition, the drug has a specific hydrolyzable joint that can be connected to the payload, and this unique design guarantees its effective activity in TROP-2-expressing cells and adjacent microenvironments, further enhancing the anti-cancer effect.
Why is it an anti-cancer weapon for triple-negative breast cancer?
Triple-negative breast cancer (TNBC) is one of the most difficult types of breast cancer to treat. Triple negative means that the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) are all negative, which makes endocrine therapy or HER2-targeted therapy (such as trastuzumab, paltozumab, etc.) basically ineffective.
But it is more gratifying that most TNBCs express TROP-2, so it brings the hope of treating TROP-2 as a target.
Based on this, gosartolizumab was first approved by the FDA in April 2020 for the treatment of patients with metastatic TNBC, becoming the first TROP-2 targeted ADC approved for marketing.
In April 2021, the FDA expanded the previously approved indications for gosartolizumab for the treatment of locally advanced or metastatic TNBC. To date, gosartolizumab has been approved for second-line treatment of metastatic TNBC in several countries around the world.
How effective is gosartozumab?
First of all, foreign countries, according to data from which gosartozumab was fully approved by the FDA, in a global phase 3 clinical trial called ASCENT, goshatozumab reduced the risk of death of patients by 49% compared with chemotherapy, and the overall survival (OS) of the neutrality was 11.8 months in the treatment group and 6.9 months in the chemotherapy group. Gosartolizumab also reduces the risk of disease progression or death by 57 percent.
In China, a single-arm, multi-center Phase 2b registered study enrolled 80 TNBC patients in China, and the results were consistent with the results of the global Phase 3 ASCENT study, and showed similar efficacy in Chinese populations.
In short, whether foreign or domestic, relevant studies have concluded that patients with triple-negative breast cancer can prolong survival and improve their quality of life after treatment with gosartozumab.
What are the adverse reactions to gosartolizumab?
Of course, the drug also has certain adverse reactions, according to studies, the most common adverse reactions (incidence of >25%) in patients receiving gosartozumab are nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite and abdominal pain. In particular, severe diarrhea, including neutropenic colitis, requires special attention.
In patients with diarrhoea, loperamide should be initiated immediately after the infectious cause has been ruled out and supportive measures (rehydration, electrolyte replacement) should be taken as clinically indicated.
For diarrhea of grade 3 or 4 that cannot be controlled by antidiarrheal drugs, the dose of the drug should be reduced immediately.
The recommended dose of gosartozumab is 10 mg/kg once a week on days 1 and 8 of a 21-day cycle until disease progresses or unacceptable toxicity develops. Please strictly follow the doctor's instructions for specific medications.
Gosavuzumab has many more possibilities in the future
In fact, TROP-2 can be expressed in many epithelial cancers, such as urinary urothelial carcinoma, so in addition to breast cancer, gosartozumab may also be approved for targeted therapy of malignant tumors such as urinary intestinal carcinoma in the future.
The FDA has already used it in April 2021 to treat patients with locally advanced or metastatic urothelial cancer who have been treated with platinum-containing chemotherapy and PD-1 or PD-L1 inhibitors.
In addition, a number of clinical studies are also being carried out simultaneously, such as for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer.
Bibliography:
[1] State Drug Administration.June 10, 2022 Drug approval documents to be released.https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220610083017154.html
[2] Bardia A , Hurvitz S A , Tolaney S M , et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer[J]. The New England journal of medicine, 384(16):1529-1541.
[3] FDA. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. [OL]https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer.
Wu H L, Liu J, Liu F H, et al. Global antibody conjugated drug research and development trend analysis[J] . International Journal of Biologics, 2021, 44(1): 38-43. DOI: 10.3760/cma.j.cn311962-20200902-00086.
Medical Editor: Su Bangjie
Medical Review: Li Xingxing
Content Operations: Duffy
Contents Exhibit: Kogan Medical Code
