Kidney Cancer - Volume 8, issue 1

Authors: Zaemes, Jacob | McDermott, David F. | Regan, Meredith M. | Atkins, Michael B.

Article Type: Short Communication

Abstract: Over the past several years, four regimens incorporating immune checkpoint inhibitors have become widely used in the front-line setting to treat metastatic clear cell renal cell carcinoma: nivolumab with ipilimumab, axitinib with pembrolizumab, cabozantinib with nivolumab, and lenvatinib with pembrolizumab. These regimens all demonstrated favorable response rates and survival outcomes compared to sunitinib in phase III trials. As these data have matured, nivolumab with ipilimumab has been most clearly associated with durable long-term disease response and stable survival benefit. Moreover, responses obtained using nivolumab with ipilimumab are more likely to persist after treatment discontinuation compared to regimens containing a VEGFR-TKI. …These outcomes underline the value of using nivolumab with ipilimumab to pursue durable response in patients with advanced clear cell renal cell carcinoma. Show more

Keywords: Checkpoint inhibitor, metastatic ccRCC

DOI: 10.3233/KCA-240011

Citation: Kidney Cancer, vol. 8, no. 1, pp. 93-97, 2024

Authors: Heng, Daniel Y.C. | Doshi, Gurjyot K. | Dutailly, Pascale | Houchard, Aude | Lothgren, Mickael | Monnette, Alisha | Wang, Yunfei | Perrot, Valérie | Lalani, Aly-Khan A.

Article Type: Research Article

Abstract: BACKGROUND: Checkpoint inhibitor (CPI)-based therapy is recommended for first-line treatment of advanced/metastatic renal cell carcinoma (mRCC). Cabozantinib is a tyrosine kinase inhibitor (TKI) approved in the USA for treating mRCC, including after CPI-based therapy. However, data on the benefits of subsequent TKI therapy are limited. OBJECTIVE: To study the real-world use and outcomes of cabozantinib versus other TKIs after CPI-based therapy for mRCC. METHODS: This retrospective study used data from the US Oncology Network electronic health record database supplemented by chart review. Patients initiated TKI therapy between 2016 and 2021 after CPI-based therapy. The primary endpoint …was real-world response rate in the first 6 months of treatment (RR-6m; physician assessment). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Covariates were adjusted by inverse probability of treatment weighting. RESULTS: Of 485 included patients, 331 received cabozantinib and 154 another TKI. Baseline characteristics were generally similar between arms. For cabozantinib versus other TKIs, adjusted RR-6m (available for 69.3% of patients) was 62.5% versus 46.0% (rate difference: superiority, 16.5% [95% CI: 7.8–25.1], p  = 0.0002), adjusted ORR was 62.4% versus 49.4% (p  = 0.0020), adjusted median OS was 19.2 versus 19.1 months (p  = 0.7353) and adjusted median PFS was 7.9 versus 9.2 months (p  = 0.8752). CONCLUSIONS: Cabozantinib following CPI-based therapy was effective for treating mRCC in the US real-world setting. Differences in adjusted RR-6m and ORR significantly favored cabozantinib versus other TKIs. The lack of OS difference may reflect differences in post-index therapy. Show more

Keywords: Cabozantinib, renal cell carcinoma, immunotherapy, retrospective study, tyrosine kinase inhibitor

DOI: 10.3233/KCA-240005

Citation: Kidney Cancer, vol. 8, no. 1, pp. 99-114, 2024

Authors: Monda, Steven | Lara, Primo N. | Gulati, Shuchi

Article Type: Systematic Review

Abstract: 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. Show more

Keywords: Kidney cancer, metastasectomy, adjuvant, systemic therapy

DOI: 10.3233/KCA-240006

Citation: Kidney Cancer, vol. 8, no. 1, pp. 115-123, 2024

Authors: Ntowe, Koumani W. | McAdoo, Sallie | Haas, Naomi B. | Karam, Jose A. | Lara Jr. , Primo N. | Fashoyin-Aje, Ibilola | Saraiya, Biren P. | Maskens, Deborah | Pickering, Lisa | Master, Viraj A. | Zhang, Tian | Kaye, Deborah R.

Article Type: Research Article

Abstract: Background: Kidney cancer is amongst the deadliest genitourinary malignancies. Neoadjuvant systemic therapy has the potential to improve survival and overall outcomes in select patients. Enrolling patients in trials of neoadjuvant treatment for kidney cancer is challenging, which limits neoadjuvant treatment development. Objective: This study aims to develop a better understanding of the barriers patients face in kidney cancer clinical trial participation, with a particular focus on neoadjuvant trials for renal cell carcinoma. Methods: From 2022–2023, we recruited participants with a history of kidney cancer through a Qualtrics survey that was sent to the Kidney Cancer Association …(KCA) and Kidney Cancer Cure (KCCure) mailing lists and social media pages. Patient responses on demographics, clinical information, and perspectives were evaluated. Results: Ninety-four individuals completed the survey. Eighty-one percent of respondents reported not participating in clinical trials due to not being informed about potential applicable trials. Importantly, many (76%) respondents reported that prevention of cancer return was a highly important reason to participate in clinical trials. Most respondents reported a willingness to undergo a kidney biopsy (59%), and/or additional appointments (58%) and surgery delays. Conclusions: Increased patient awareness about clinical trials with the potential to delay cancer recurrence may increase patient participation in clinical trials. Clinical trial design, including additional appointments or interventions and/or minor surgery delays are not major barriers to trial participation. Show more

Keywords: Renal cell carcinoma, neoadjuvant therapy, clinical trials, enrollment, survey

DOI: 10.3233/KCA-240009

Citation: Kidney Cancer, vol. 8, no. 1, pp. 125-134, 2024

Authors: Narang, Arshit | Gebrael, Georges | Jo, Yeonjung | Thomas, Vinay Mathew | Li, Haoran | Fortuna, Gliceida Galarza | Sayegh, Nicolas | Tandar, Clara | Tripathi, Nishita | Chigarira, Beverly | Srivastava, Ayana | Hage Chehade, Chadi | Nordblad, Blake | Maughan, Benjamin L. | Agarwal, Neeraj | Swami, Umang

Article Type: Research Article

Abstract: 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. Show more

Keywords: Immunotherapy, metastasis, renal cell carcinoma, survival outcomes, tyrosine kinase inhibitors

DOI: 10.3233/KCA-240016

Citation: Kidney Cancer, vol. 8, no. 1, pp. 135-142, 2024