Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study
Takuto Shimizu, Makito Miyake, Nobutaka Nishimura, Kuniaki Inoue, Koyo Fujii, Yusuke Iemura, Kazuki Ichikawa, Chihiro Omori, Mitsuru Tomizawa, Fumisato Maesaka, Yuki Oda, Tatsuki Miyamoto, Keiichi Sakamoto, Keisuke Kiba, Masahiro Tanaka, Nobuo Oyama, Eijiro Okajima, Ken Fujimoto, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Kazumasa Torimoto, Nobumichi Tanaka, Kiyohide Fujimoto
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.