Immunotherapy maintenance versus immunotherapy after progression on platinum-based chemotherapy in the treatment of locally advanced or metastatic urothelial cancer

Abstract (English)

Introduction: Checkpoint inhibitors immunotherapy is a standard part of treatment for locally advanced or metastatic urothelial carcinoma (mUC). Initial clinical trials showed benefit of atezolizumab or pembrolizumab immunotherapy after progression to platinum-based chemotherapy. A few years later Javelin Bladder 100 (JB100) study was demonstrated longer progression-free survival (PFS) and overall survival if avelumab immunotherapy maintenance was added in patients without progression on platinum-based chemotherapy. In our institution, we initially treated patients with immunotherapy after progression, and after the appearance of the JB100 study, we included avelumab in the maintenance therapy. In this paper, we compared two forementioned strategies. Methods: In our study, 56 subjects were included, 35 received atezolizumab after progression, while 21 patients were treated with avelumab in maintenance therapy. There were 41 male patients in the study, the median age was 65 years (41-78). We defined four endpoints PFS1 calculated from the start of immunotherapy to progression or death, PFS2 from the start of chemotherapy to progression to immunotherapy (as second line or maintenance) or death, OS1 from the start of immunotherapy to death and OS 2 from the start of chemotherapy to death Results: PFS2 and OS2 did not differ in relation to patient gender, age, diagnosis of synchronous or metachronous metastases, presence of mixed histology, presence of bone and lung metastases. Patients with lymph node metastases had a longer PFS2, while patients without liver metastases had a longer OS. PFS1 and PFS 2 were longer in the group treated with maintenance therapy with avelumab 7 vs. 3 months; p=0.0002 HR 0.27 (CI 0.14-0.53) and 17 vs. 10 months; p=0.021 HR 0.47 (CI 0.25-0.89), respectively. Also, OS 1 and OS 2 were longer in the group that received maintenance therapy: 10 vs 5 months; p=0.0006 HR 0.32 (CI 0.16-0.61) and 19 vs. 11 months; p=0.0251 HR 0.47 (CI 0.24-0.91), respectively. Two-year OS1 was 44% vs 8% in the maintenance therapy group versus the second-line immunotherapy group. Conclusions: In our group of patients, the maintenance therapy strategy showed benefits in terms of PFS and OS compared to the second line of treatment. The reason is probably not a difference in the effectiveness of immunotherapy agents, but a better performance of patients after stabilization with chemotherapy, more time for immunotherapy to start working, and a certain number of platinum-refractory
patients in the second-line group.