PD58-12: Cross-reactivity between the first-line chemotherapy and subsequent immunotherapy in patients with unresectable or metastatic urothelial carcinoma

Tomoko Hamaya*, Shingo Hatakeyama, Kai Ozaki, Kazutaka Okita, Yasuhiro Hashimoto, Chikara Ohyama, Hirosaki, Japan

Introduction: Immunotherapy is beneficial in patients with unresectable locally advanced or metastatic UC. The JAVELIN Bladder 100 trial demonstrated that the survival benefit of avelumab maintenance therapy in selected patients with favorable response to the first-line chemotherapy. This observation may suggest that a favorable response to first-line chemotherapy might be associated with a favorable response to subsequent immunotherapy. However, not enough data is available for the cross-reactivity between the first-line chemotherapy and subsequent immunotherapy. Therefore, we retrospectively investigated the cross-reactivity between the first-line chemotherapy and subsequent immunotherapy in patients with advanced UC.

Methods: We evaluated 218 patients with advanced UC (T4, N positive, or M1) who received systemic, platinum-based, first-line chemotherapy from May 2003 to August 2021. The primary objective was comparison of overall survival between the patients treated with or without second-line immune checkpoint inhibitor (ICI) who had no progressive disease (PD) =4 cycles of the first-line chemotherapy (the non-PD =4 group). Secondary objective was to evaluate overall survival between the patients treated with or without second-line ICI who had PD =4 cycles of the first-line chemotherapy (the PD =4 group).

Results: The median age was 71 years. The numbers of patients with the non-PD =4 and PD =4 groups were 84 and 134, respectively. In the non-PD =4 group, we observed significantly longer overall survival in patients treated with ICI than those without. The difference in the median survival reached 37 months (26 vs. 63 months, P = 0.039).
Conversely, there was no significant difference in overall survival in the PD =4 group. The multivariable Cox regression analysis showed that administration of ICI, performance status, and non-PD =4 were significantly associated with overall survival.

Conclusions: The favorable tumor response to the first-line chemotherapy was significantly associated with longer survival in advanced UC patients with subsequent immunotherapy than those without. There may be cross-reactivity between chemotherapy and subsequent immunotherapy.

Source of Funding: none