Urothelial carcinoma is a common malignant tumor in China, and the most important bladder cancer can be the most common malignant tumor in China 12 of [1]. Due to the influence of Chinese herbal medicine and other factors, the rare upper urothelial carcinoma in Europe and the United States also has a high incidence rate in China[2]< /span>.
Fortunately, urothelial carcinoma will produce symptoms of hematuria in the early stage of the disease, and most patients have can be found in time. For example, among bladder cancer patients in China, 74.1% were diagnosed in the early stage, and the tumor had not invaded the muscle layer, but 25.2% of the patients still had tumor infiltrated into the muscle layer at the time of diagnosis, and even distant metastasis span>[3].
At present, platinum-based chemotherapy is still the first-line treatment of choice for patients with advanced urothelial carcinoma. The survival period is about 12 to 15 months.[4]. However, after platinum-based chemotherapy resistance, the treatment options for patients with advanced urothelial carcinoma are very limited. Taxanes and vinflunine recommended by NCCN and ESMO guidelines have a response rate of only about 10% and a median survival time of 7 to 8 patients. Months[5].
urothelial carcinoma including urothelial carcinoma of renal pelvis, ureter, and lower urinary tract of bladder and urethra1Nobel Prize results in urothelial cancerBut there are still limitations
In 2019, the immunotherapy that just won the Nobel Prize is popular all over the world Also forays into urothelial cancer. PD-1 inhibitor K drug reduces the risk of death by 30% and prolongs median survival by 2.8 months in platinum-resistant metastatic urothelial carcinoma [6], and was therefore approved for the treatment of advanced urothelial carcinoma.
However, immunotherapy still has the problem of low effective rate, the objective response rate is only 21.1%, and the disease control rate is 38.5% and 48.5% of patients still progressed after treatment. The disease control rate of immunotherapy is even lower than that of chemotherapy. Advanced urothelial carcinoma still has a large unmet need for treatment.
2 New hope brought by “ADC magic drug”
In urothelial carcinoma, 83% of patients have moderate to high levels of Trop-2 Express. A recent study showed that the positive rate of Trop-2 in Chinese urothelial carcinoma population was as high as 90.3%[ 7]. This makes Trop-2 targeted therapy a new hope for the treatment of advanced urothelial cancer.
gosatuzumab (Sacituzumab govetcan , SG)is the world’s first approved antibody-drug conjugate targeting Trop-2(ADC) , by targeting Trop-2, the powerful cytotoxic drug SN-38 carried on the antibody is precisely delivered to the tumor to kill cancer cells. How effective is it for advanced urothelial cancer?
TROPHY-U-01 tested the efficacy of goxatuzumab in patients with advanced urinary Antitumor activity and safety in epithelial carcinoma[8]. A total of 113 patients with advanced urothelial carcinoma who had received platinum and PD-1 mAbs were recruited for this study. The median age was 66 years, 78% were male, 66.4% had visceral metastases, and 33.6% had liver metastases. The median number of prior treatments was 3 (range 1-8).
Of these patients, 6 patients were Complete remission after Zizumab treatment, partial remission in 25 patients, and stable disease in 11 patients for more than 6 months. Goxatuzumab achieved an objective response rate of 27.4% and a clinical benefit rate of 37.2%. The median time to onset of action was as short as 1.6 months.
Objective response rate with goxatuzumab was 27.4%, up to 77%% measurable Lesion shrinkageAfter a median follow-up of 9.1 months, the median progression-free survival of the 113 patients was 5.4 months, the median overall survival was 10.9 months, and the median treatment Lasted 7.2 months. Of the 31 patients who were in remission after treatment, 30 were still alive at the time of data cutoff, and 4 remained in remission.
31 patients in remission after treatment were still alive at the time of data cutoff, and 4 patients remained in remission span>
In the study, common adverse reactions included diarrhea, nausea, fatigue, hair loss, neutropenia, decreased appetite, anemia, vomiting and leukopenia. Most of them are common clinical adverse reactions, which can be effectively managed through supportive care or dose adjustment. The proportion of patients who discontinued treatment due to adverse reactions was only 6%, showing that goxatuzumab was well tolerated.
At present, the FDA has approved goxatuzumab for the treatment of patients with locally advanced or Treatment of metastatic urothelial carcinoma. In China, a marketing application for goxatuzumab has been submitted and is expected to be approved soon. Chinese patients may soon be able to use this “ADC magic drug”.
References:
[1 ]. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. International journal of cancer, 2015, 136(5): E359-E386.< /span>
[2]. Chen X P, Xiong G Y, Li X S, et al. Predictive factors for worse pathological outcomes of upper tract urothelial carcinoma: experience from a nationwide high‐volume centre in China[J]. BJU international, 2013, 112(7): 917-924.
[3]. Li K, Lin T, Xue W, et al. Current status of diagnosis and treatment of bladder cancer in china–analyses of chinese bladder cancer consortium database[J]. Asian Journal of Urology, 2015, 2(2): 63-69.
[4]. Bukhari N, Al-Shamsi HO, Azam F. Update on the treatment of metastatic urothelial carcinoma[J]. The Scientific World Journal, 2018, 2018.
[5]. Niegisch G, Gerullis H, Lin S W, et al. A real-world data stud y to evaluate treatment patterns, clinical characteristics and survival outcomes for first-and second-line treatment in locally advanced and metastatic urothelial cancer patients in Germany[J]. Journal of Cancer, 2018, 9(8): 1337.
[6]. Fradet Y, Bellmunt J, Vaughn D J, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of > 2 years of follow-up[J]. Annals of Oncology, 2019, 30(6): 970-976.
[7]. Fan Y, Li Q, Shen Q, et al. Head-to-Head Comparison of the Expression Differences of NECTIN-4, TROP-2, and HER2 in Urothelial Carcinoma and Its Histologic Variants[J]. Frontiers in oncology, 2022, 12: 858865.
[8]. Tagawa S T, Balar A V, Petrylak D P, et al. TROPHY-U-01: A phaseII open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors[J]. Journal of Clinical Oncology, 2021, 39(22): 2474-2485.