Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

Abstract

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30–40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63–22.4) p < 0.0001; HR 3.63 (1.97–6.69), p < 0.0001; HR 2.75 (1.35–5.59), p = 0.0053; and HR 3.17 (1.00–10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02–0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma: a multicentre retrospective cohort study

“…In our study, poor response and survival outcome of bone and liver metastases was significant, while lymph nodes metastases correlated with higher ORR. These results are consistent with published data in the literature for patients treated with ICI 57–59. Makrakis et al showed lower response rates and shorter OS for bone and liver metastases on retrospective data from 917 mUC treated with ICI as first or ≥ second line, but higher ORR for lymph node-confined metastases 57.…”

“… 57 A retrospective multicentric Japanese study reported shorter ORR for bone metastases in a cohort of patients treated with Pembrolizumab for mUC. 58 Similar results have also been reported from prospective trials. 60 61 In the IMvigor210 phase II trial, the ORR on Atezolizumab was 32% for lymph node-confined metastases, and only 8% for liver metastases, data for bone metastases were not reported.…”

“…Makrakis et al showed lower response rates and shorter OS for bone and liver metastases on retrospective data from 917 mUC treated with ICI as first or ≥ second line, but higher ORR for lymph node-confined metastases 57. A retrospective multicentric Japanese study reported shorter ORR for bone metastases in a cohort of patients treated with Pembrolizumab for mUC 58. Similar results have also been reported from prospective trials 60 61.…”

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

“…Makrakis et al showed lower response rates and shorter OS for bone and liver metastasis on retrospective data from 917 mUC treated with ICI as 1 st or ≥ 2 nd line, but higher ORR for lymph node confined metastasis [57]. A retrospective multicentric Japanese study reported shorter ORR for bone metastasis in a cohort of patients treated with Pembrolizumab for mUC [58].…”

Insights into Urologic Cancer

“…Immunotherapy has shown promise in the treatment of BCA, but response rates can vary. Shimizu et al [ 12 ] investigated, in a multicenter retrospective analysis, the outcome of patients with urothelial cancer undergoing pembrolizumab therapy. They showed that bone metastases responded only infrequently to pembrolizumab.…”