Kidney cancer (Clifton, Va.)最新文献

Background: Cabozantinib, a tyrosine kinase inhibitor (TKI), is a prevalent second-line (2 L) therapy and was approved for use after progression on TKIs. However, the 1 L treatment setting has changed since the approval of cabozantinib monotherapy in salvage therapy settings.

Objective: To assess the differential effectiveness of cabozantinib after prior progression on 1 L ipilimumab with nivolumab (IPI + NIVO) compared to programmed death receptor-1 (PD-1) or PD-1 ligand (PD-L1) inhibitors (PD1/L1i) with TKIs.

Methods: Utilizing a nationwide electronic health record (EHR)-derived de-identified database, we included patients with metastatic clear cell renal cell carcinoma (mccRCC) who received 1 L treatment with an immune checkpoint inhibitor (ICI)-based combination and 2 L treatment with cabozantinib monotherapy. These patients were categorized based on the type of 1 L ICI-based combination received: IPI + NIVO vs. PD1/L1i with TKI. Real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) were summarized using Kaplan-Meier curves and compared using Cox-proportional hazard models adjusted for International mRCC Database Consortium (IMDC) risk groups.

Results: Among 12,285 patients with metastatic renal cell carcinoma, 237 were eligible and included. Median rwTTNT was 8 months for the IPI + NIVO subgroup and 7.5 months for the PD1/L1i + TKI subgroup (HR 1.05, 95% CI: 0.74-1.49, p = 0.8). Median rwOS was 17 months for IPI + NIVO and 16 months for PD1/L1i + TKI subgroup (HR 0.79, 95% CI: 0.52-1.20, p = 0.3).

Conclusions: Cabozantinib remains effective as a 2 L therapy for mccRCC independent of the type of prior 1 L ICI-based combination. Further research is needed to validate these findings and explore the ideal sequencing of therapies.

Background: Pembrolizumab is established as adjuvant therapy for patients with high-risk clear cell renal cell carcinoma (ccRCC) after resection. Patients with completely resected metastatic disease (M1 NED) seem to have greater benefit from adjuvant pembrolizumab in both disease-free survival (DFS) and overall survival (OS); yet, with other agents, adjuvant therapy has not been shown to improve survival. As newer therapies evolve, it is important to understand the efficacy of systemic agents in this patient population.

Objective: We aimed to systematically review available trials investigating adjuvant therapy after metastasectomy in RCC.

Methods: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through January 2024. For inclusion, studies were required to include completely resected patients with known metastatic RCC. Patients with only locally advanced and/or regional nodal involvement (N1) alone were excluded. Titles and abstracts were screened to identify articles for full-text, and then a descriptive review was performed.

Results: A total of 149 articles were initially identified. Ultimately 9 articles published before the end of January 2024 met our inclusion criteria and were included in the analysis. Data were extracted and organized to reflect the role of adjuvant treatment - both targeted therapies as well as immunotherapy in patients who had undergone metastasectomy and rendered M1 NED. With the exception of pembrolizumab, adjuvant therapy in M1 NED was not found to be associated with improved survival.

Conclusions: Pembrolizumab appears to benefit M1 NED ccRCC patients after resection even more than other high-risk ccRCC patients. Yet, this same benefit has not been seen with other agents. Future research should focus on trying to establish which M1 NED patients benefit from adjuvant treatment.

Liquid biopsy techniques have developed rapidly in recent years and demonstrated success in cancer detection, disease characterization, and ongoing disease monitoring. These components, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and cell-free DNA (cfDNA), offer minimally invasive diagnostic tools that provide valuable insights into the genomic landscape of tumors. Its applications have expanded to include various malignancies, including renal cell carcinoma (RCC). RCC, a heterogeneous malignancy, poses unique diagnostic and therapeutic challenges. Up to 40% of patients experience recurrence or metastasis following initial surgical resection, necessitating the need for precise diagnostic and prognostic tools. The application of liquid biopsy in RCC, particularly through CTCs and ctDNA/cfDNA, holds significant promise. This review first delves into the various methodologies of CTC and cfDNA/ctDNA detection in RCC and highlights their roles in RCC management. Next, we discuss in depth about current existing evidence for the utilization of liquid biopsy in RCC diagnosis, prognosis, treatment outcomes prediction and association with the progression of the disease. Despite advancements, RCC's biological features, including low ctDNA shedding and significant intratumoral heterogeneity, present challenges in the clinical application of liquid biopsy. The review also discusses the limitations of current techniques and emphasizes the need for standardized protocols and further validation in large, diverse cohorts. Future directions include integrating liquid biopsy with advanced imaging techniques and leveraging artificial intelligence to improve RCC diagnostics and patient management. With continued refinement, liquid biopsy could become an essential tool in personalized oncology, improving outcomes for RCC patients.

[This corrects the article DOI: 10.3233/KCA-210117.].

Background: Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses.

Objective: The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features.

Methods: We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords "renal cell cancer" and "immune checkpoint inhibitors" and equivalents were used and all original publications between July 2016 and July 2021 were included.

Results: We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features.

Conclusion: The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.

Background: Cabozantinib is among the most potent tyrosine kinase inhibitors (TKIs) FDA-approved for metastatic renal cell carcinoma (mRCC). Effective treatments after progression on cabozantinib salvage therapy are limited. Dose escalation for other TKIs has been shown to afford added disease control.

Objective: We sought to evaluate whether dose escalation of cabozantinib (Cabometyx^®) from conventional doses in select patients with limited treatment options offered additional disease control. We asked how cabozantinib dose increases may affect circulating drug levels.

Methods: We identified patients with mRCC at the University of Texas Southwestern Medical Center who were treated with cabozantinib dose escalation to 80 mg after progressing on conventional cabozantinib 60 mg. We then queried leading kidney cancer investigators across the world to identify additional patients. Finally, we reviewed pharmacokinetic (PK) data to assess how higher doses impacted circulating levels by comparison to other formulations (Cometriq^® capsules).

Results: We report six patients treated at two different institutions with cabozantinib-responsive disease and good tolerability, where cabozantinib was dose escalated (typically to 80 mg, but as high as 120 mg) after progression on 60 mg, a strategy that resulted in added disease control (median duration, 14 months; 95% Confidence Interval [CI]: 8 - Not Estimable[NE]). Four patients (66.7%) had disease control lasting at least 1 year. No grade III/IV adverse events were identified in this small, select, cohort. A comparison of PK data to FDA-approved cabozantinib 140 mg capsules suggest that cabozantinib 80 mg tablets results in comparable exposures.

Conclusions: mRCC patients with cabozantinib responsive disease and reasonable tolerability may benefit from dose escalation at progression.

Background: Substantial racial and socioeconomic disparities in metastatic RCC (mRCC) have persisted following the introduction of targeted oral anticancer agents (OAAs). The relationship between patient characteristics and OAA access and costs that may underlie persistent disparities in mRCC outcomes have not been examined in a nationally representative patient population.

Methods: Retrospective SEER-Medicare analysis of patients diagnosed with mRCC between 2007-2015 over age 65 with Medicare part D prescription drug coverage. Associations between patient characteristics, OAA receipt, and associated costs were analyzed in the 12 months following mRCC diagnosis and adjusted to 2015 dollars.

Results: 2,792 patients met inclusion criteria, of which 32.4%received an OAA. Most patients received sunitinib (57%) or pazopanib (28%) as their first oral therapy. Receipt of OAA did not differ by race/ethnicity or socioeconomic indicators. Patients of advanced age (> 80 years), unmarried patients, and patients residing in the Southern US were less likely to receive OAAs. The mean inflation-adjusted 30-day cost to Medicare of a patient's first OAA prescription nearly doubled from $3864 in 2007 to $7482 in 2015, while patient out-of-pocket cost decreased from $2409 to $1477.

Conclusion: Race, ethnicity, and socioeconomic status were not associated with decreased OAA receipt in patients with mRCC; however, residing in the Southern United States was, as was marital status. Surprisingly, the cost to Medicare of an initial OAA prescription nearly doubled from 2007 to 2015, while patient out-of-pocket costs decreased substantially. Shifts in OAA costs may have significant economic implications in the era of personalized medicine.