653 Background: Response to PD1/L1 inhibitors per RECIST 1.1 or immune-related (ir)-RECIST is associated with improved overall survival (OS). Patients (Pts) with stable disease (SD)> 6 months has been proposed to capture benefit; however, SD constitutes a heterogeneous group impacted by pace of disease progression and intervals between radiographic imaging. In contrast, minor tumor regressions that are <partial response (PR) by RECIST1.1 are discerned without formal radiology review and may reflect the activity of immunotherapy, which is known to be durable compared to other therapies. We previously reported that any regression of tumor (ART) on PD1/L1 inhibitor therapy in 1216 patients across solid tumors showed significant association with improved OS and facilitated the discrimination of SD patients with better OS (El Zarif T, ESMO Congress Sep 2022). We aimed to further investigate and validate the association of ART with OS in mUC pts receiving PD1/L1 inhibitors who exhibited SD. Methods: Deidentified data from mUC pts treated with PD1/L1 inhibitors at AdventHealth institutions in the USA were reviewed retrospectively. Demographic data (age, sex), setting (untreated vs. post-therapy), sites of metastasis, performance status (PS) and prior therapy were collected. We assessed the association of overall ART (complete response CR + partial response PR + those with SD and ART) and ART among those with SD by RECIST 1.1 with OS. Kaplan Meier curves were used to estimate OS with 95% intervals, and log rank tests were used to compare survival distributions between groups. Results: A total of 66 patients were evaluable. The median age was 69.5 years, 48 (72.7%) were male and 32 (48.5%) were therapy naive. Overall, ART (CR+PR+SD with ART) and SD as best response were seen in 38 (57.6%) and 27 (40.9%) pts, respectively. Among pts with SD, ART was seen in 14 pts. Median OS was 22.1 months (95% CI: 15.7–33.2) in the overall group of pts with ART vs 4.6 months (95% CI 1.7–12.9) in the absence of ART (p < 0.001). Among SD patients, median OS was 31 months (95% CI: 18.2–52.3) in patients with ART and 3.6 months (0.4–15.6) in the absence of ART (p ≈ 0.023). When examining the groups by RECIST1.1, the PD+SD group had a median OS of 7.2 months (95% CI: 3.6-18.2) and the PR+CR group exhibited a median OS of 22.1 months (14.0–34.0) (p ≈ 0.024). When examining the outlier groups by RECIST1.1, the PD group had a median OS of 9.8 months (95% CI: 1.2–13.4) and the PR+CR group exhibited a median OS of 22.1 months (14.0–34.0) (p ≈ 0.008). Conclusions: ART was validated to be associated with improved OS in patients with mUC receiving PD1/L1 inhibitor therapy. ART is a readily determined intermediate endpoint capturing OS benefit in pts with advanced solid tumors including mUC and facilitates the discrimination of OS benefit among SD patients.
Alhayek et al. (Sun,) studied this question.