Real-world use of PD-(L)1 immune checkpoint inhibitors (CPI) and post-CPI treatment patterns and outcomes in ovarian and endometrial cancer (2014-2021).
Authors: Craft Miranda , Craggs Christopher , Ravel Nayia , Chan John K , Lin Yvonne Gail 
Published: June 2022

e18795

Background: Given the rapid adoption of immune checkpoint inhibitors (CPI) in gyn cancers, we sought to characterize the real-world (RW) use of CPI, treatment patterns post-CPI, and clinical outcomes of patients (pts) with ovarian (OC) or endometrial (EC) cancer in the US. Methods: A retrospective analysis of pts with OC/EC treated with ≥1 line of systemic therapy after 1/1/2014 within the Flatiron Health (FH) real-world data (RWD) Electronic Health Record (EHR) was conducted. FH is a longitudinal EHR-derived de-identified database from ̃280 US cancer clinics. Treatment patterns after 1st CPI were identified and analyzed in pts with ≥ 6 months of observation from starting CPI per the EHR. Descriptive comparisons were performed using χ2 or t-tests, as appropriate. Time-to-next treatment (i.e., time from starting initial CPI to 1st subsequent therapy post-CPI/death) served as a PFS proxy. Pre-specified survival analyses via Kaplan-Meier methods were used for CPI therapy (i.e., 1L, 2L, 3L) and class of post-CPI therapy. Results: 7639 pts (5415 OC, 2224 EC) received ≥1 line of therapy. Median age was 65 [57-73] (OC) and 66 [60-72] (EC); 67% were white; 84% were in community practices; 34% had commercial insurance; 69% OC and 59% EC had Stage III/IV disease; 10% OC had a BRCA1/2 mutation; 12% EC were MSI-H/dMMR. 130 (2.4%) OC pts and 326 (14.7%) EC pts received CPI at any point of their cancer care. Among pts receiving CPI, CPI was given as 1st, 2nd, and ≥3rd line of therapy in 13.8%, 18.5%, 67.7% of OC pts, and 24.6%, 32.5%, 42.9% of EC pts. Median time-to-next treatment for OC pts on CPI was 5.52, 4.60, and 4.04 months in the 1L, 2L, and 3L setting, respectively (p=0.98), and for EC pts, 9.23, 6.41, and 4.27 months in the 1L, 2L, and 3L setting, respectively (p=0.05). 68 (52.3%) OC pts received subsequent therapy post-CPI; 39 (30.0%) died < 90 days post-CPI; 4 (3.1%) died > 90 days post-CPI, and 19 (14.6%) were alive with no evidence of subsequent therapy. In contrast, 110 (33.7%) of EC pts received subsequent therapy post-CPI; 98 (30.0%) died < 90 days post-CPI; 9 (2.8%) died > 90 days post-CPI, and 105 (32.2%) were alive with no evidence of subsequent therapy. Of 68 OC pts who received subsequent therapy after CPI, 38.2% received chemo only, 25.0% additional CPI (alone or in combo), 16.2% targeted therapy, and 14.7% chemo + bevacizumab. Of 110 EC pts who received subsequent therapy, 38.2% received chemo only, 29.1% additional CPI (alone or in combo), 20.0% targeted therapy, and 6.4% chemo + bevacizumab. Conclusions: Checkpoint inhibitors were used in later lines of therapy more notably in OC than EC. Time-to-next treatment on CPI did not seem to vary by line of therapy among OC pts, whereas time-to-next treatment on CPI appeared longer when CPI was used earlier among EC pts. This study reveals early observations into the RW use and sequencing of checkpoint inhibitors in ovarian and endometrial cancers.