Spray-on organic/inorganic films: a general method for the formation of functional nano- to microscale coatings.

journal article2010 Dec 27importe

Chemotherapy following immune checkpoint inhibitors in patients with locally advanced or metastatic urothelial carcinoma

BACKGROUND: Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). METHODS: In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities. RESULTS: Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (< or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients. CONCLUSION: This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data

Everolimus or sunitinib as first-line treatment of metastatic papillary renal cell carcinoma: A retrospective study of the GETUG group (Groupe d'Etude des Tumeurs Uro-Genitales)

International audienceBackground: Two phase II trials (NCT00688753 and NCT00541008) reported efficacy data of sunitinib and everolimus in first-line treatment of metastatic papillary renal cell carcinoma (mpRCC). Although most patients receive sunitinib or a mammalian target of rapamycin (mTOR) inhibitor in first-and second-line treatment, the optimal strategy remained unknown. Material and methods: In 23 centres of the Groupe d'Etude des Tumeurs Urogenitales group, after centralised pathological review, we analysed retrospectively progression-free survival (PFS) of patients with mpRCC treated in first-line treatment (PFS-1) with sunitinib or everolimus (primary end-point), PFS in second-line treatment (PFS-2), overall survival (OS), objective response rate, disease control rate (DCR), overall sequence and prognostic factors for OS (secondary end-points). Results: One hundred thirty-eight patients (119 men and 19 women), median age 62.5 years, with mpRCC type 1 (n = 24) or non-type 1 (n = 114), received first-line sunitinib (n = 107) or everolimus (n = 31). With a median follow-up of 92 months, we found no significant difference between the treatment groups in terms of PFS-1 (5.5 versus 6.2 months) and DCR (69% versus 83%). Ninety-eight patients received a second-line treatment, 69% with mTOR inhibitors after sunitinib and 100% with tyrosine kinase inhibitors after everolimus, with similar DCR (64% versus 58%), median PFS-2 (3.4 versus 4.8 months) and OS (16.0 versus 20.3 months). No factor was prognostic for PFS-1, whereas leukocytosis, anaemia and the time from diagnosis to first systemic therapy &lt; 1 year were prognostic for OS. We found no prognostic difference between both pRCC subtypes. The International Metastatic Renal Cell Database Consortium risk factors were prognostic for OS. Conclusion: Sunitinib and everolimus had similar efficacy in first-line treatment of patients with mpRCC. 2021 Elsevier Ltd. All rights reserved

Clinical outcome after progressing to frontline and second-line Anti–PD-1/PD-L1 in advanced urothelial cancer[Formula presented]

Background: Immune checkpoint inhibitors (ICIs) are approved for first-line (cisplatin unfit, PD-L1+) and platinum-refractory urothelial carcinoma (UC). Still, most patients experience progressive disease (PD) as the best response. Although higher response rates to subsequent systemic treatment (SST) have been described, post-PD outcome data are scarce. Objective: To examine the outcome of UC patients who received SST and no SST after progressing to ICIs. Design, setting, and participants: A retrospective analysis of UC patients progressing to frontline or later-line anti–PD-1/PD-L1 therapy in 10 European institutions was conducted between March 2013 and September 2017. Intervention: Post-PD management as per standard practice. Outcome measurements and statistical analysis: Overall survival (OS) was analyzed with a Kaplan-Meier model. Cox regression was used for multivariate analysis (MV). Impact of SST on OS was examined with a time-varying covariate model. Results and limitations: A total of 270 UC patients with PD to ICIs (69 frontline, 201 later line) were analyzed. Of the patients, 57% of frontline-ICI-PD and 34% of later-line-ICI-PD patients received SST, and SST had an impact on OS in MV (frontline: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.10–0.51, p < 0.001; later line: HR 0.22, 95% CI 0.13–0.36, p < 0.001). In the frontline-ICI-PD group, median OS with and without SST was 6.8 mo (95% CI 5.0–8.6) and 1.9 mo (95% CI 0.9–3.0), respectively. High disease burden (three or more metastatic sites: HR 2.49, p = 0.03; simultaneous liver/bone metastases: HR 3.93, p = 0.03) predicted worse survival. In later-line-ICI-PD group, response to ICIs (HR 0.37, p = 0.03), longer exposure to ICIs (HR 0.89, p = 0.002), and bone metastasis (HR 2.42, p < 0.001) predicted survival. The retrospective nature of this study and a lack of certain parameters limit the interpretation of our analysis. Conclusions: Patients progressing to frontline ICIs are at risk of early death, excluding them from experiencing potential benefit from chemotherapy Patient summary: Our analysis suggests that outcomes after failing immunotherapy are poor, particularly in UC patients who received no prior chemotherapy