Impact of the objective response to and number of cycles of platinum‐based first‐line chemotherapy for metastatic urothelial carcinoma on overall survival of patients treated with pembrolizumab

Abstract

To investigate the impact of the number of cycles and objective response to chemotherapy on overall survival in patients with metastatic urothelial carcinoma treated with pembrolizumab. Methods: This multicenter, retrospective study included 755 patients from 59 institutions with advanced, chemoresistant urothelial carcinoma who received pembrolizumab. The associations of the overall survival with the number of cycles and best objective response were investigated using Cox multiple regression analysis. Results: Overall, 391 patients received standard first-line chemotherapy and pembrolizumab as a second-line treatment, and were included in the final analysis. Of the 391 patients, 185 received less than four cycles, 134 received four to six cycles and 72 received more than six cycles of first-line chemotherapy. An objective response (complete or partial response) to chemotherapy was observed in 145 patients (37.1%). Univariate analysis showed that the overall survival of patients who received more than six cycles or responded to chemotherapy (complete or partial response) was significantly longer than that of patients who received less than four cycles or did not respond to chemotherapy (stable or progressive disease). At multivariate levels, no correlations were observed between overall survival and the number of cycles of or the response to chemotherapy. Conclusions: Therapeutic benefit of pembrolizumab can be expected irrespective of the objective response to and number of cycles of platinum-based first-line chemotherapy.

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

“…Our data showed that the overall response rate to subsequent chemotherapy after pembrolizumab failure was 20.9%, which is comparable to previous results in similar settings 7,8 . This is also consistent with expected results from patients who previously failed chemotherapy without previous ICI exposure, 9,10 suggesting that chemotherapy responses are maintained irrespective of previous exposure to ICIs. Of the 115 patients with subsequent chemotherapy, four had CR to chemotherapy, all of which were rechallenged cases of gemcitabine and cisplatin chemotherapy.…”

Significant Improvement of Prognosis After the Advent of Immune Checkpoint Inhibitors in Patients with Advanced, Unresectable, or Metastatic Urothelial Carcinoma: A Propensity Score Matching and Inverse Probability of Treatment Weighting Analysis on Real-World Data

“…Most previous studies have analyzed and reported survival rates from the date of ICI initiation. [2][3][4][5][6]16 The pivotal trial, KEYNOTE-045, reported that median OS in the pembrolizumab group was 10.3 months as compared to 7.4 months in the chemotherapy group (P = 0.002), resulting in a 2.9-month survival benefit from the initiation of pembrolizumab or investigator's choice of chemotherapy. A recent report from the Japan Urological Oncology Group demonstrated a positive correlation between response to pembrolizumab and response to chemotherapy, 16 implying that time-totreatment failure of first-line chemotherapy is closely associated with that of second-line ICI therapy.…”

“…[2][3][4][5][6]16 The pivotal trial, KEYNOTE-045, reported that median OS in the pembrolizumab group was 10.3 months as compared to 7.4 months in the chemotherapy group (P = 0.002), resulting in a 2.9-month survival benefit from the initiation of pembrolizumab or investigator's choice of chemotherapy. A recent report from the Japan Urological Oncology Group demonstrated a positive correlation between response to pembrolizumab and response to chemotherapy, 16 implying that time-totreatment failure of first-line chemotherapy is closely associated with that of second-line ICI therapy. Therefore, to discuss the real survival benefit from the advent of ICI, we need to evaluate survival from the initiation of first-line chemotherapy, not from the initiation of second-line therapy.…”

Effect of active anticancer therapy on serologic response to SARS‐CoV‐2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma

“… 4 , 5 , 6 Systemic chemotherapy and ICIs are two immunoregulation agents frequently administered to patients with advanced UC. 7 , 8 , 9 , 10 , 11 , 12 Treatment with ICIs in combination or ICIs plus TKIs is considered the standard of care for patients with metastatic RCC. 13 , 14 , 15 , 16 , 17 , 18 Furthermore, immune‐related AEs are closely associated with high‐dose steroid administration in patients treated with ICIs, and steroid use has been associated with impaired humoral response to SARS‐CoV‐2 mRNA vaccines in patients with cancer.…”