First-Line Atezolizumab Is Suitable in Platinum-Based Chemotherapy Ineligible mUC

Frontline atezolizumab (Tecentriq) monotherapy yielded a clinically relevant benefit in patients with locally advanced or metastatic urothelial cancer (mUC) who had high comorbidities and/or functional status and were not eligible to receive platinum-based chemotherapies based on clinical assessment, according to findings from the retrospective, multicenter, observational IMFLAME study.

Data presented from the study at the 2025 Genitourinary (GU) Cancers Symposium showed that at a median follow-up of 7.5 months, patients treated in the real-world setting (n = 91) experienced a 12-month survival rate of 41.8%; the 18- and 24-month rates were 30.8% and 19.8%, respectively. The objective response rate (ORR) was 45.2% and patients had a median duration of response (DOR) of 19 months (95% CI, 9.8-28.3). Findings also revealed that the median progression-free survival (PFS) was 4.1 months (95% CI, 1.5-6.7) and the median overall survival (OS) was 9.7 months (95% CI, 5.2-14.3). Investigators also noted that an ECOG performance status of 2 or 3 was identified as a prognostic factor for survival and was associated with worse PFS and OS outcomes.

“Univariate analyses based on hematologic and biochemical markers before the start of atezolizumab treatment have shown that patients with [mUC with] normal levels of hemoglobin, neutrophils, lymphocytes, albumin, and/or lactate dehydrogenase [LDH] had significantly longer OS compared [with] patients with abnormal values. Similarly, normal neutrophil counts, albumin levels, and LDH levels were associated with longer PFS,” investigators wrote in a poster presentation of the data.

Examining the Retrospective Study and Patient Characteristics

Investigators noted that although the current frontline standard of care for patients with mUC is enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) and patients who are ineligible for this regimen may receive platinum-based chemotherapy followed by maintenance avelumab (Bavencio), a subset of patients are not eligible for these therapies due to significant comorbidities and poor performance status. Therefore, the retrospective study was conducted to evaluate the clinical outcomes of patients who received frontline therapy with the humanized PD-L–targeted monoclonal antibody atezolizumab in Spain due to the ineligibility for platinum-based chemotherapy.

Data on patients with locally advanced or metastatic urothelial cancer were extracted from medical charts and included patient demographics, clinical characteristics, outcomes, and treatment patterns. The primary end point was the 12-month survival rate and secondary end points included 18- and 24-month survival rates as well as OS, PFS, ORR, DOR, potential prognostic factors associated with survival, and safety.

Additionally, patients enrolled were a median age of 77 years when diagnosed with advanced disease. Most patients were male (78.0%), Caucasian (96.6%), former smokers (65.9%), and had PD-L1–positive disease (85.0%). They had stage IIIB (4.4%), IVA (45.1%), and IVB (50.5%) disease and ECOG performance statuses of 0 (6.3%), 1 (53.2%), 2 (30.4%), and 3 (10.1%). Comorbidities included hypertension (54.9%), dyslipidemia (35.2%), cardiovascular disease (34.1%), diabetes mellitus (29.7%), chronic obstructive pulmonary disease (9.9%), and other (88.9%).

Patients also has metastases sites of visceral (42.9%)—which included the lungs (26.4%), liver (13.2%), and other (16.5%)—and nonvisceral (71.4%) such as the lymph nodes (59.3%), bone (22.0%), and other (9.9%).

Safety and Outcomes by Hematologic and Biochemical Markers

Regarding the safety of atezolizumab observed in the real-world study, 26.4% of patients experienced a treatment interruption; interruptions were due to urinary tract infection (17.1%), immune-mediated adverse effects (AEs; 14.6%), non-safety/effectiveness physician decision (12.2%), patient decision (12.2%), and other reasons (43.9%). Further, 92.3% of patients discontinued treatment most commonly due to progressive disease or death (70.2%). Reasons for discontinuation also included non-safety/effectiveness physician decision (8.3%), worsening of comorbidities/functional decline (7.1%), immune-mediated AEs (7.1%), patient decision (2.4%), and other reasons (4.8%).

Additionally, 5 of the 15 immune-mediated AEs that occurred were grade 3 severity or higher and included colitis, hyperglycemia, dermatitis, thrombocytopenia and acute kidney injury.

Moreover, the PFS and OS of patients with normal vs abnormal levels of several markers were examined in those treated with the monoclonal antibody. The median OS was as follows for those with normal vs abnormal levels of hemoglobin (18.9 vs 6.1 months; log-rank P = .011), neutrophils (13.2 vs 3.0 months; log-rank P = .016), lymphocytes (11.6 vs 2.5 months; log-rank P = .019), and albumin (9.5 vs 2.7 months; log-rank P < .001). The median PFS was as follows for those with normal vs abnormal levels of hemoglobin (7.0 vs 3.3 months; log-rank P = .186), neutrophils (7.0 vs 2.3 months; log-rank P = .028), lymphocytes (5.5 vs 2.2 months; log-rank P = .239), albumin (5.5 vs 1.5 months; log-rank P < .001), and LDH (5.5 vs 2.2 months; log-rank P = .0035).

“Further research is essential to optimize patient selection and management strategies, especially in fragile patients who may not be considered for novel regimens with antibody-drug conjugates,” investigators wrote in their conclusion.

Reference

Gómez de Liaño Lista A, Romero-Laorden N, Gajate P, et al. Effectiveness and safety of first-line atezolizumab in locally advanced or metastatic urothelial cancer: the IMFLAME study. J Clin Oncol. 2025;43(suppl 5):720. doi:10.1200/JCO.2025.43.5_suppl.720