New adjuvant therapy for bladder cancer (MIBC)! The pathological complete remission rate (PCR) of imfinzi + lynparza was 50%

February 17, 2020 / BIOON / -- recently, a single arm phase II study (nct03534492) published at the 2020 American Society of clinical oncology urogenital cancer symposium (ASCO-GU 2020) held in San Francisco showed that AstraZeneca The combination of imfinzi (English Feifan, common name: durvalumab, duvalizumab) and lynparza (Lipitor, common name: olaparib, olapari) in the new adjuvant treatment of muscle infiltrating bladder cancer (MIBC) showed strong curative effect: the pathological complete remission rate (PCR) reached 50% In this study, 29 patients with ct2-t4a resectable MIBC were enrolled These patients were treated with imfinzi 6-8 weeks before planned cystectomy, 1500 mg once every 4 weeks for 2 months (maximum 2 doses / cycle), and lynparza twice a day for 150 mg twice a day for 56 days (28 days, 2 cycles) Twenty patients who received cystectomy were evaluated for efficacy and 27 for safety In terms of ECoG physical state score, 55.2% of the patients in this study were 0 (the activity ability was completely normal, no significant difference from before the onset of the disease), 44.8% of the patients were 1 (able to walk and engage in light physical activity, but not engage in heavy physical activity) The median age of the patients was 71 years old In TNM stage, pT2 accounted for 82.2%, pT3 for 7.1% and pT4 for 7.1% About 14.3% of the patients had lymph node spread The results showed that 10 out of 20 patients (50%) received complete pathological remission (PCR), which was defined as no tumor in bladder and lymph node In the safety evaluation, the tolerance of imfinzi + lynparza combined therapy was good In the 27 patients who evaluated the safety, only 3 cases of level 4 adverse events (one case for wound enucleation, one case for bleeding, one case for septic shock, respectively) and 3 cases of treatment interruption (due to personal decision, progressive disease, deterioration of chronic obstructive pulmonary disease) occurred At present, researchers are analyzing the expression of PD-L1 and the pattern of immune infiltration in blood samples before and after treatment All tumor samples were sequenced Juan Francisco Rodriguez Moreno, MD, oncologist of the comprehensive cancer center of CICC, HM hospital, Madrid, Spain, who reported the study, said: "this study is not intended to assess the efficacy of these two drugs With this in mind, the data on efficacy are interesting because 50% of the PCR rate is superior to other therapies in new adjuvant therapy The main purpose of this study is to determine the impact of this combination on molecular characteristics, but biomarker data are currently being analyzed and are expected to be published above ESMO 2020 in Madrid " Rodriguez Moreno said that the standard care for muscle infiltrating bladder cancer (MIBC) is radical cystectomy, which is rarely cured Although neoadjuvant chemotherapy based on cisplatin is the standard perioperative care, only a few patients can benefit from it Therefore, new adjuvant therapy is needed Recent evidence suggests that immunocheckpoint inhibitors can be incorporated into this therapeutic environment, and that they have been approved by the US FDA for the treatment of patients with advanced bladder cancer who are difficult to treat or unqualified for platinum chemotherapy However, the highest response rate of MIBC patients to immunosuppressive monotherapy was about 30% Imfinzi has been shown to be effective in patients with advanced urothelial carcinoma (UC) who have received chemotherapy with platinum, and is currently being evaluated for first-line treatment, including monotherapy and combination therapy with tremelimumab, an anti-CTLA-4 therapy At the ASCO meeting in 2019, the preliminary results of the single arm trial of imfinzi + tremelimumab combined therapy for high-risk MIBC patients who did not meet the neoadjuvant chemotherapy conditions of cisplatin showed that in 21 patients who had undergone complete cystectomy, the PCR rate of the combined therapy was 43% (9 / 21), and in 14 patients (67%) the tumor stage decreased PARP inhibitors, such as lynparza, can amplify DNA damage, increase the burden of tumor mutation, and make bladder tumors more immunogenic by increasing the production of new antigens and up regulating the expression of PD-L1 In this way, lynparza and imfinzi may play a synergistic role Original source: ASCO-GU 2020: Abstract 542