Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study.

INTRODUCTION: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents. We aim to assess the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients enrolled in the NIVOREN trial. MATERIALS AND METHODS: All patients with BM at inclusion were included in our study. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE). RESULTS: Among 720 patients treated with nivolumab, 194 presented BM at inclusion. The median follow-up was 23.9 months. Median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (p = 0.0023). The difference was not statistically significant after adjustment (p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, p = 0.0045), as well as the ORR (14.8% versus 23.3%). SRE occurred for 36% of patients with BM. A post-hoc analysis evaluating the impact of bone-targeting agents (BTA) on SRE incidence showed a significant benefit of BTA on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895]). CONCLUSION: Nivolumab is associated with shorter PFS, and lower ORR in RCC patients with BM. Our study suggests that BTA in association with immunotherapy decreases the incidence of SRE.

First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

The development of antiangiogenic treatments, followed by immune checkpoint inhibitors (ICI), has significantly changed the management of metastatic clear cell renal cell cancer. Several phase III trials show the superiority of combination therapy, dual immunotherapy (ICI-ICI) or ICI plus tyrosine kinase inhibitors (TKI) of the vascular endothelium growth factor (VEGF) over sunitinib monotherapy. The question is therefore what is the best combination for a given patient? A strategy based on the International Metastatic Database Consortium (IMDC) classification is currently recommended with pembrolizumab + axitinib, cabozantinib + nivolumab, and lenvatinib + pembrolizumab (for all patients) or nivolumab + ipilimumab (for patients with intermediate or poor risk), which are the first-line treatment standards of care. However, several issues remain unresolved and require further investigation, such as the PD-L1 status, the relevance of possible options based on the patient's profile, and consideration of second-line and subsequent treatments.

Cross-Cultural Adaptation and Psychometric Validation of the French Version of the FAMCARE-Patient (FFP-16) Questionnaire for Outpatients With Advanced-Stage Cancer.

CONTEXT: Satisfaction is known to be correlated with the quality of care; it indicates the adequacy of the caregivers' responses in meeting the needs and expectations of patients. The FAMCARE-Patient questionnaire has been used to quantify satisfaction level in outpatients with advanced-stage cancers. OBJECTIVES: To translate and cross-culturally adapt the FAMCARE-Patient questionnaire for French patients and to evaluate the psychometric properties of this version. METHODS: The original questionnaire was translated into French and adapted to French cultural context by an expert committee. The French FAMCARE-Patient Version 16 (FFP-16) was then pilot tested among 51 patients. Subsequently, psychometric properties were evaluated in a cross-sectional study by administrating the new tool to 176 adult outpatients with advanced-stage cancer who underwent oncological care at our university hospital. RESULTS: We performed a confirmatory factor analysis and assessed the reliability and validity of the questionnaire. The one-factor structure was confirmed, and it had an acceptable fit with a comparative fit index and root mean square error of approximation of 0.93 and 0.07, respectively. Internal reliability was high as shown by Cronbach's alpha (α = 0.95). Reproducibility was very good (intraclass correlation coefficient 0.91). The FFP-16 score was independent of the Eastern Cooperative Oncology Group and the overall Edmonton Symptom Assessment Scale distress scores. It was significantly but weakly correlated with anxiety, well-being, and overall quality of life (Spearman's correlation coefficient = -0.18, -0.20, and 0.30, respectively; P < 0.05). CONCLUSION: We found the FFP-16 questionnaire to be a reliable and valid instrument for the assessment of satisfaction in French outpatients with advanced-stage cancer.

Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes).

BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.

Metastatic renal cell carcinoma treated sequentially with multiple VEGF receptor-targeted inhibitors--a case report.

Six targeted agents [sorafenib, sunitinib, temsirolimus, bevacizumab (plus interferon), everolimus and pazopanib] have been approved for the treatment of patients with metastatic renal cell carcinoma. As disease progression is inevitable, most patients will receive several lines of treatment. However, the choice regarding which sequence of drugs to use remains unclear, particularly concerning the drug class, i.e. those targeting the vascular endothelial growth factor (receptor) [VEGF(R)] pathway versus those acting on the mammalian target of rapamycin pathway. There appears to be no absolute crossresistance between tyrosine kinase inhibitors (TKIs) acting on the VEGF(R) pathway, and there have been numerous reports of two TKIs being successfully used in sequence. We report the case of a 63-year-old woman who responded for 24 months to three successive lines of treatment with different TKIs (sunitinib, axitinib and sorafenib). This suggests that TKIs targeting VEGFR should be considered as individual drugs and not as a single class.

[Acute respiratory failure and septic shock induced by Mycobacterium bovis. A rare side effect of intravesical BCG therapy]. / Atteinte respiratoire sévère et choc septique à Mycobacterium bovis. Une complication rare de la BCG thérapie intravésicale.

INTRODUCTION: Intravesical bacillus Calmette-Guerin (BCG) therapy, recommended for superficial bladder tumors, triggers side effects in fewer than 5% of patients. The most severe side effects, however, are septic shock and acute respiratory failure. CASE: A 70-year-old man was hospitalized for septic shock with acute respiratory and renal failure after intravesical instillation of BCG, which was identified in the gastric aspiration sample. Treatment with rifampicin, ethambutol, isoniazid, and corticosteroid therapy, as well as standard reanimation measures, led to the patient's recovery. DISCUSSION: This case shows the potentially severe side effects of intravesical BCG instillation. Although this treatment is well tolerated in more than 95% of patients and its systemic complications can be effectively treated, these side effects can be life-threatening.