Role of Bone Metastases in Patients Receiving Immunotherapy for Pre-Treated Urothelial Carcinoma: The Multicentre, Retrospective Meet-URO-1 Bone Study

Raggi, Daniele; Giannatempo, Patrizia; Marandino, Laura; Pierantoni, Francesco; Maruzzo, Marco; Lipari, Helga; Banna, Giuseppe Luigi; Giorgi, Ugo De; Casadei, Chiara; Naglieri, Emanuele; Buti, Sebastiano; Bersanelli, Melissa; Stellato, Marco; Santini, Daniele; Vignani, Francesca; Roviello, Giandomenico; Veccia, Antonello; Caffo, Orazio; Losanno, Tania; Calabrò, Fabio; Mucciarini, Claudia; Pignata, Sandro; Necchi, Andrea; Maïo, Massimo Di; Group, on behalf of MEET-URO

doi:10.1016/j.clgc.2021.12.008

Cited by 13 publications

(9 citation statements)

References 30 publications

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Section: Discussionsupporting

confidence: 93%

“…In our study, poor response and survival outcome of bone and liver metastasis was significant, while lymph nodes metastasis correlated with higher ORR. These results are consistent with published data in the literature for patients treated with ICI [57-59]. Makrakis et al showed lower response rates and shorter OS for bone and liver metastasis on retrospective data from 917 mUC treated with ICI as 1 st or ≥ 2 nd line, but higher ORR for lymph node confined metastasis [57].…”

Section: Discussionsupporting

confidence: 89%

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Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

Labidi,

Meti,

Barua

et al. 2023

Preprint

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BackgroundAnti-PD-1/L1 immune checkpoint inhibitors (ICI) are indicated for metastatic urothelial cancer (mUC), however, only a minority of patients will derive therapeutic benefit. Strong predictive and prognostic factors are lacking. We investigated if clinical variables were associated with ICI outcomes in mUC.MethodsWe performed a multi-center retrospective cohort study of patients with mUC who received anti-PD-1/L1 ICI for metastatic disease between 2016-2021 at 3 Canadian cancer centres. Clinical characteristics, including demographics, BMI, metastatic sites, neutrophil-to-lymphocyte ratio (NLR), objective response, and survival were abstracted from chart review. ICI treatment response was determined by investigator assessment of clinical and radiologic parameters. Fisher’s exact test was used to assess differences in response rates between groups. Log rank and Cox regression models were used to assess overall survival (OS).ResultsWe identified 135 patients with mUC who received anti-PD1/L1 ICI. A BMI ≥ 25 was significantly correlated to a higher overall response rate (ORR) to ICI (45.4% vs 16.3%, P = 0.020). After a median follow-up of 14.5 months, patients with BMI ≥ 30 experienced significant longer median OS 24.8 months vs. 14.4 months for 25 ≤ BMI < 30 and 8.5 months for BMI < 25 (P = 0.012). The ORR was significantly less in the presence of bone metastasis 16% vs 41% P = 0.006, and liver metastasis 16% vs 39% P = 0.013. Conversely, the presence of metastatic lymph nodes was significantly correlated with higher ORR 40% vs 20% P = 0.032. The median OS for patients with bone metastasis was 7.3 months vs 18 months in the absence of bone metastasis (P < 0.001). Patients with liver metastasis had a median OS of 8.6 months compared to 15 months for those without liver metastasis (P = 0.006). For lung metastasis, median OS was 8.7 months compared to 17.3 months (P = 0.004). No statistical difference was shown in OS for lymph nodes metastasis, with a median of 13.5 months vs 12.7 months (P = 0.175). Patients with NLR ≥ 4 had a significant worse OS (8.2 months vs 17.7 months P = 0.0001). In multivariate analysis, BMI ≥ 30, bone metastasis and NLR ≥ 4 were independent prognosis factor for OS.ConclusionsOur data identified BMI and bone metastasis as novel, independent, clinical biomarkers that were strongly and independently associated with ICI response and survival in mUC. External validation of these data in a larger study and investigations into the mechanisms behind these findings are warranted.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

Labidi,

Meti,

Barua

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In our study, poor response and survival outcome of bone and liver metastases was significant, while lymph nodes metastases correlated with higher ORR. These results are consistent with published data in the literature for patients treated with ICI 57–59. Makrakis et al showed lower response rates and shorter OS for bone and liver metastases on retrospective data from 917 mUC treated with ICI as first or ≥ second line, but higher ORR for lymph node-confined metastases 57.…”

Section: Discussionsupporting

confidence: 90%

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

Labidi,

Meti,

Barua

et al. 2024

BMJ Open

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ObjectivesImmune 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

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“…Patients with BM had inferior survival compared to those without BM. 17 In our study, the impact of BM on subsequent treatment with ICI was not evaluated. Taken together, these data would suggest that BM may be an independent predictor of survival both in patients receiving chemotherapy and those receiving second-line ICI.…”

Section: Discussionmentioning

confidence: 91%

The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy

et al. 2022

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Background: In metastatic urothelial cancer (mUC), bone metastasis (BM) are associated with significant morbidity and mortality, yet their role as an independent prognostic variable remains unclear. We aimed to determine the impact of BM on overall survival (OS) in patients with mUC treated with first-line platinum-based chemotherapy (PBC). Methods: mUC patients receiving PBC at the Princess Margaret Cancer Center, Tom Baker Cancer Center, or Cross Cancer Institute from January 2005 to January 2018 were identified retrospectively using central pharmacy database records. Patient disease, treatment, and response characteristics were collected. Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method. Variables reaching significance ( p < 0.05) in univariable analysis (UVA) of survival (OS) were included in multivariable analysis (MVA) (Cox). Results: Overall, 376 patients with a median follow-up of 16.8 (range: 2.2–218.3) months were included. Median age was 67 (range: 28–91) years, 76% were male, 63% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, and 41% had BM. All patients received first-line PBC. Patients with BM had inferior median PFS (4.9 months (95% CI 3.6–6.2) versus 6.5 months (95% CI 5.4–7.6), p = 0.03) and median OS (8.8 months (95% CI 7.8–9.7) versus 10.8 months (95% CI 9.1–12.5), p = 0.002). In UVA, ECOG PS 2–3 ( p < 0.001), presence of BM ( p = 0.002), and WBC count ⩾ 11,000 cells/mm3 ( p = 0.001) were associated with inferior survival. Prior cystectomy ( p < 0.001) and lack of progression (stable disease, partial or complete response) on treatment was associated with improved OS ( p < 0.001). These variables maintained significance in MVA. Conclusion: In this retrospective study, mUC patients with BM had worse OS suggesting that BM may be an independent negative prognostic factor and including BM as a stratification factor in future mUC clinical trial designs may be warranted. A greater focus must be placed on novel therapeutic strategies to better manage BM to reduce both morbidity and mortality.

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Role of Bone Metastases in Patients Receiving Immunotherapy for Pre-Treated Urothelial Carcinoma: The Multicentre, Retrospective Meet-URO-1 Bone Study

Cited by 13 publications

References 30 publications

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

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

The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy

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