Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma: a multicentre retrospective cohort study.

Objectives: Immune checkpoint inhibitors (ICIs) are indicated for metastatic urothelial cancer (mUC), but predictive and prognostic factors are lacking. We investigated clinical variables associated with ICI outcomes.
Methods: We performed a multicentre retrospective cohort study of 135 patients who received ICI for mUC, 2016-2021, at three Canadian centres. Clinical characteristics, body mass index (BMI), metastatic sites, neutrophil-to-lymphocyte ratio (NLR), response and survival were abstracted from chart review.
Results: We identified 135 patients and 62% had received ICI as a second-line or later treatment for mUC. A BMI ≥25 was significantly correlated to a higher overall response rate (ORR) (45.4% vs 16.3%, p value=0.020). Patients with BMI ≥30 experienced longer median overall survival (OS) of 24.8 vs 14.4 for 25≤BMI<30 and 8.5 months for BMI <25 (p value=0.012). The ORR was lower in the presence of bone metastases (16% vs 41%, p value=0.006) and liver metastases (16% vs 39%, p value=0.013). Metastatic lymph nodes were correlated with higher ORR (40% vs 20%, p value=0.032). The median OS for bone metastases was 7.3 versus 18 months (p value <0.001). Patients with liver metastases had a median OS of 8.6 versus 15 months (p value=0.006). No difference for lymph nodes metastases (13.5 vs 12.7 months, p value=0.175) was found. NLR ≥4 had worse OS (8.2 vs 17.7 months, p value=0.0001). In multivariate analysis, BMI ≥30, bone metastases, NLR ≥4, performance status ≥2 and line of ICI ≥2 were independent factors for OS.
Conclusions: Our data identified BMI and bone metastases as novel clinical biomarkers that were independently associated with ICI outcomes in mUC. External and prospective validation are warranted.
Competing Interests: Competing interests: Nicholas Meti—Honoraria: Takeda, Novartis. Consulting: Takeda, Seagen, AstraZeneca, Pfizer. Srikala S Sridhar—Consulting: Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, BMS, Eisai, EMD Serono, Gilead, Ipsen, Janssen, Merck, Pfizer, Seagen; Research funding (Institution): Janssen, Seagen, EMD Serono. Rossanna C Pezo—Honoraria: Pfizer, Novartis, BMS, Merck, Sanofi, Gilead, AstraZeneca; Research funding (Institution): Merck, Novartis, Pfizer, Taiho, Jazz Pharmaceuticals, ZymeWorks, AstraZeneca. Cristiano Ferrario—Honoraria: Pfizer, Bayer, Novartis, Roche, Bayer, Knight therapeutics, AstraZeneca, Merck, Astellas Pharma; Consulting—Merck, Novartis, AstraZeneca, Roche; Research funding (Institution): Merck, Novartis, Pfizer, Lilly, ZymeWorks, AstraZeneca, Janssen Oncology, Bayer, Astellas Pharma, Roche, Sanofi, Seattle Genetics, Semonix Pharmaceuticals, Bicycle Therapeutics, Immunomedics. Susanna Cheng—Consulting: AstraZeneca, Merck. April A N Rose—Consulting: EMD Serono, Advanced accelerator applications/Novartis; Research funding (Personal): Canadian Institutes of Health Research CIHR, Canadian Cancer Society, Conquer Cancer Foundation, Jewish General Hospital Foundation, TransMedTech Institute, Canada Foundation of Innovation; Research Funding (Institution): AstraZeneca, Merck, Pfizer, Seattle Genetics; Employment: Family member Merck. Soumaya Labidi, Mengqi Li, Sonia V Del Rincon, Reeta Barua, Jamila Riromar, Di Maria Jiang, Nazanin Fallah-Rad, Adrian G Sacher: no competing interests.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)