Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first‐line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

Background The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype‐specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first‐line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC‐STBSG) sites. Methods The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression‐free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval‐censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. Results Three hundred three patients from 18 EORTC‐STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score–matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2‐9.7 months), 8.2 months (95% CI, 5.2‐10.1 months), and 4.8 months (95% CI, 2.3‐6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52‐0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9‐47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7‐33.4 months; HR, 0.65; 95% CI, 0.40‐1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0‐36.3 months; HR, 0.66; 95% CI, 0.43‐0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. Conclusions This is the largest retrospective study of first‐line treatment for advanced leiomyosarcoma. In the propensity score–matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials

Non-Clear Cell Renal Cell Carcinomas: From Shadow to Light

International audienc

Les actualités marquantes du congrès Targeted Anticancer Therapies — TAT 2016

International audienc

Conditional immune toxicity rate in patients with metastatic renal and urothelial cancer treated with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Although the incidence and prevalence of irAEs have been well characterized in the literature, less is known about the cumulative incidence rate of irAEs. We studied the cumulative incidence of irAEs, defined as the probability of irAE occurrence over time and the risk factors for irAE development in metastatic urothelial carcinoma (mUC) and renal cell carcinoma (mRCC) patients treated with ICIs.MethodsWe identified a cohort of patients who received ICIs for mUC and mRCC. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) V.5.0 guidelines. The monthly incidence of irAEs over time was reported after landmark duration of therapy. Cumulative incidence of irAEs was calculated to evaluate the time to the first occurrence of an irAE accounting for the competing risk of death. Prognostic factors for irAE were assessed using the Fine and Gray method.ResultsA total of 470 patients were treated with ICIs between July 2013 and October 2018 (mUC: 199 (42.3%); mRCC: 271 (57.7%)). 341 (72.6%) patients received monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received dual ICI therapy. Overall, 186 patients (39.5%) experienced an irAE at any time point. Common irAEs included hypothyroidism (n=42, 22.6%), rush and pruritus (n=36, 19.4%), diarrhea/colitis (n=35, 18.8%), transaminitis (n=32, 17.2%), and pneumonitis (n=14, 7.5%). Monthly incidence rates decreased over time; however, 17 of 109 (15.6%, 95% CI: 9.4% to 23.8%) experienced their first irAE at least 1 year after treatment initiation. No differences in cumulative incidence were observed based on cancer type, agent, or irAE grade. On multivariable analysis, combined ICI therapy with another ICI or with targeted therapy (p<0.001), first-line ICI therapy (p=0.011), and PD-1 inhibitor therapy (p=0.007) were all significantly associated with irAE development.ConclusionsThis study quantitates the incidence of developing irAEs due to ICI conditioned on time elapsed without irAE development. Although the monthly incidence of irAEs decreased over time on therapy, patients can still develop delayed irAEs beyond ICI discontinuation, and thus, continuous vigilant monitoring is warranted

Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: lessons learned from European excellence centers

Purpose There is no consensus on which items of Enhanced Recovery After Surgery (ERAS) should and should not be implemented in radical cystectomy (RC). The aim of this study is to report current practices across European high-volume RC centers involved in ERAS.Methods Based on the recommendations of the ERAS society, we developed a survey with 17 questions that were validated by the Young Academic Urologists-urothelial group. The survey was distributed to European expert centers that implement ERAS for RC. Only one answer per-center was allowed to keep a representative overview of the different centers.Results 70 surgeons fulfilled the eligibility criteria. Of note, 28.6% of surgeons do not work with a referent anesthesiologist and 25% have not yet assessed the implementation of ERAS in their center. Avoiding bowel preparation, thromboprophylaxis, and removal of the nasogastric tube were widely implemented (> 90%application). On the other hand, preoperative carbohydrate loading, opioid-sparing anesthesia, and audits were less likely to be applied. Common barriers to ERAS implementation were difficulty in changing habits (55%), followed by a lack of communication across surgeons and anesthesiologist (33%). Responders found that performing a regular audit (14%), opioid-sparing anesthesia (14%) and early mobilization (13%) were the most difficult items to implement.Conclusion In this survey, we identified the ERAS items most and less commonly applied. Collaboration with anesthesiologists as well as regular audits remain a challenge for ERAS implementation. These results support the need to uniform ERAS for RC patients and develop strategies to help departments implement ERAS

Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: lessons learned from European excellence centers

Purpose: There is no consensus on which items of Enhanced Recovery After Surgery (ERAS) should and should not be implemented in radical cystectomy (RC). The aim of this study is to report current practices across European high-volume RC centers involved in ERAS. Methods: Based on the recommendations of the ERAS society, we developed a survey with 17 questions that were validated by the Young Academic Urologists–urothelial group. The survey was distributed to European expert centers that implement ERAS for RC. Only one answer per-center was allowed to keep a representative overview of the different centers. Results: 70 surgeons fulfilled the eligibility criteria. Of note, 28.6% of surgeons do not work with a referent anesthesiologist and 25% have not yet assessed the implementation of ERAS in their center. Avoiding bowel preparation, thromboprophylaxis, and removal of the nasogastric tube were widely implemented (> 90%application). On the other hand, preoperative carbohydrate loading, opioid-sparing anesthesia, and audits were less likely to be applied. Common barriers to ERAS implementation were difficulty in changing habits (55%), followed by a lack of communication across surgeons and anesthesiologist (33%). Responders found that performing a regular audit (14%), opioid-sparing anesthesia (14%) and early mobilization (13%) were the most difficult items to implement. Conclusion: In this survey, we identified the ERAS items most and less commonly applied. Collaboration with anesthesiologists as well as regular audits remain a challenge for ERAS implementation. These results support the need to uniform ERAS for RC patients and develop strategies to help departments implement ERAS