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Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for unresectable PM has consisted of a platinum-based drug plus pemetrexed, leading to an overall survival of approximately 12 months. The dramatic therapeutic scenario of PM has recently changed with the entry into the clinic of immune checkpoint inhibition, which has proven to be an effective approach to improve the survival of PMpatients. The aimof the present review is to provide a comprehensive overview of the most promising immunotherapeuticbased strategies currently under investigation for advanced PM. [ABSTRACT FROM AUTHOR]

We performed a retrospective analysis on 56 patients with metastatic renal cell carcinoma who received at least 1 systemic treatment line after cabozantinib. Median OS after cabozantinib was 7.7 months, while median TTF after cabozantinib was 2.8 months. Further investigation is needed in this clinical context. Background: Cabozantinib, a potent multityrosine kinases inhibitor (TKI), has demonstrated overall survival (OS) benefit over everolimus in patients previously treated with VEGFR TKI for metastatic Renal Cell Carcinoma (mRCC). The efficacy of systemic treatments after cabozantinib failure has not been investigated. Materials and Methods: We conducted a retrospective study on patients receiving systemic treatment after cabozantinib failure in heavily pretreated patient with mRCC. We assessed Time to Treatment Failure (TTF), OS and objective response rate (ORR). Results: Among 150 patients treated with cabozantinib in our institution, 56 (37.3%) received subsequent systemic therapy and were eligible for the analysis. IMDC prognostic group was good, intermediate and poor in 11 (19.6%), 24 (42.9%) and 11 (19.6%) patients, respectively. Cabozantinib was administered mainly as a second (41.1%), or third (33.9%) line treatment. axitinib or immune-checkpoint inhibitors were the subsequent treatment in 18 (34.8%) patients for each everolimus (n:16, 28.6%), other angiogenesis inhibitors (n:4, 7.1%) TTF and OS from subsequent systemic therapy after cabozantinib failure were 2.8 months (95%CI 1.9-3.7) and 7.7 months (95%CI 4.4-10.8), respectively. ORR was 8.7% and 2 patients with axitinib and 2 patients treated with Immune checkpoint inhibitors achieved a partial response. Conclusion: Overall, activity of systemic therapies after cabozantinib was limited. [ABSTRACT FROM AUTHOR]

Introduction: Cabozantinib is an oral tyrosine kinase inhibitor that is approved for the treatment of metastatic renal cell carcinoma (mRCC). Cabozantinib is a weak base that exhibits a pH‐dependent solubility profile in vitro which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPIs). The purpose of this study was to investigate whether PPI use has an impact on the efficacy, safety, and residual concentration (Ctrough) of cabozantinib in patients with mRCC. Materials and Methods: This is a retrospective review of a prospectively collected electronic database of patients with mRCC who received cabozantinib at Gustave Roussy between February 2014 and December 2018. The Kaplan‐Meier method was used for survival analysis and the Cox proportional‐hazard model for uni‐ and multivariate analysis. In parallel, we conducted a pharmacokinetic study of cabozantinib in a distinct cohort of 50 mRCC patients, in which cabozantinib Ctrough was assayed using a validated tandem mass spectrometry–liquid chromatography method. Results: We identified 99 patients treated with cabozantinib, including 43 patients being PPI users. With a median follow‐up of 30.3 months, PPI users showed similar progression‐free survival and overall survival outcomes compared with PPI nonusers. Similarly, the incidence of adverse events was not significantly different between the PPI users and nonusers, although PPI users required dose reductions more often. In the independent pharmacokinetic cohort, of whom 21 received PPI concomitantly, Ctrough was similar between the two groups. Conclusion: In line with the pharmacologic data, the concomitant use of PPI does not significantly impact the efficacy or safety of cabozantinib in patients with mRCC. Implications for Practice: Drug interactions, especially between targeted therapies and proton pump inhibitors (PPI), were shown to potentially impact the outcomes of cancer patients. Cabozantinib, a current therapeutic standard in metastatic renal cell carcinoma (mRCC), exhibits a pH‐dependent solubility profile, which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPI). At the present time, there is no evidence regarding the effect of PPIs on cabozantinib's efficacy and safety in patients with mRCC. This study found that the concomitant use of PPI during cabozantinib treatment in mRCC patients does not appear to impact the residual concentration, efficacy, and safety of cabozantinib in a real‐life context. This article reports on the effect of proton pump inhibitors on the pharmacology, efficacy and safety outcomes of patients with metastatic renal cell carcinoma treated with cabozantinib. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results. • First cohort of poor PS mRCC treated with front line ICI-based combination therapy. • The survival outcomes were inferior to that reported in pivotal trials. • No significant differences in ORR, PFS or OS were seen between NI and AP. • Both NI and AP were well tolerated without significant differences between them. [ABSTRACT FROM AUTHOR]