scholarly journals Second-Line Therapies in the Changing Landscape of First-Line Therapies for Metastatic Clear Cell Renal Cell Cancer

ONCOLOGY ◽  
2021 ◽  
pp. 306-310
Author(s):  
Tiffany Shaw ◽  
Hannah Lee ◽  
Robert Figlin
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Single Agent ◽  
Current Data ◽  
Treatment Modalities ◽  
Second Line ◽  
First Line ◽  
Line Setting

In recent years, first-line therapies for metastatic renal cell carcinoma (mRCC) have shifted to a combination of immune checkpoint inhibitors or a combination of antiangiogenesis tyrosine kinase inhibitors (TKIs) and immunotherapy. This has led to a need to address standard-of-care treatment in the second-line setting. Our review presents an analysis of current and upcoming data to guide treatment decisions. After progression on nivolumab plus ipilimumab, current data favor monotherapy TKI with cabozantinib or axitinib. Current literature for second-line therapy given after combination TKI plus immunotherapy shows the strongest evidence for either single-agent cabozantinib or combination everolimus with lenvatinib. Investigations are ongoing for the role of TKIs with immunotherapy in the second-line setting. Novel agents, such as HIF2α inhibitors, are currently being studied as single agents and in combination with other treatment modalities in efforts to improve patient outcomes in mRCC.

scholarly journals Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Rohini Sharma ◽  
Leila Motedayen Aval
Keyword(s):  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hepatocellular Cancer ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Second Line ◽  
Research Strategies ◽  
First Line ◽  
Line Setting

Until recently, the treatment landscape for hepatocellular cancer (HCC) was dominated by tyrosine kinase inhibitors (TKIs) which offered an overall survival (OS) benefit when used both in the first-and second-line setting compared to best supportive care. However, the treatment landscape has changed with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of HCC with significant improvement in OS and progression free survival reported with combination atezolizumab and bevacizumab compared to sorafenib in the first-line setting. Nonetheless, the response to ICIs is 20–30% and invariably patients will progress. What remains unclear is which therapeutics should be used following ICI exposure. Extrapolating from the evidence base in renal cell carcinoma, subsequent therapy with TKIs offers both a response and survival benefit and are recommended by European guidelines. However, there are a number of novel therapies emerging that target mechanisms of ICI resistance that hold promise both in combination with ICI or as subsequent therapy. This paper will discuss the evidence for ICIs in HCC, the position of second-line therapies following ICIs and research strategies moving forward.

Avelumab and axitinib combination therapy for the treatment of advanced renal cell carcinoma

2020 ◽  
Vol 16 (36) ◽  
pp. 3021-3034
Author(s):  
Maryam Soleimani ◽  
Lucia Nappi ◽  
Christian Kollmannsberger
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitor ◽  
Single Agent ◽  
First Line ◽  
Line Setting

Owing to an improved understanding of the immunobiological profile of renal cell carcinoma (RCC), the past few years have ushered in significant changes in systemic therapies for advanced stage RCC. First-line treatment with single-agent tyrosine kinase inhibitors (TKI) has been virtually replaced for most patients by immunotherapy combinations. The first of such treatments was the dual immune checkpoint inhibitor combination of ipilimumab and nivolumab. More recently, the combination of an immune checkpoint inhibitor and a TKI has also moved into the first-line setting. This review summarizes the pharmacologic properties, evidence for use and safety of avelumab, a PD-L1 inhibitor and axitinib a small-molecule TKI, each as monotherapy, and in combination for the management of metastatic RCC.

scholarly journals Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

2014 ◽  
Vol 8 (11-12) ◽  
pp. 398 ◽  
Author(s):  
Suzanne Richter ◽  
Jo-An Seah ◽  
Gregory R Pond ◽  
Hui K Gan ◽  
Mary J. Mackenzie ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Pivotal Phase ◽  
Line Therapy ◽  
To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

scholarly journals Treatment options in advanced renal cell carcinoma after first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors

2016 ◽  
Vol 10 (11-12) ◽  
pp. 242 ◽  
Author(s):  
Naveen S. Basappa
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Renal Cell ◽  
Vascular Endothelial ◽  
Second Line ◽  
First Line ◽  
Line Setting ◽  
Endothelial Growth Factor

Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago, and since then a number of therapeutic options have been developed. Vascular endothelial growth factor targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes.

scholarly journals Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3750
Author(s):  
Yasir Khan ◽  
Timothy D. Slattery ◽  
Lisa M. Pickering
Keyword(s):  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Therapeutic Options ◽  
Current Status ◽  
Vegf Receptor ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.

scholarly journals A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment

2013 ◽  
Vol 3 (4) ◽  
pp. 281 ◽  
Author(s):  
Mark Warren ◽  
Peter M. Venner ◽  
Scott North ◽  
Tina Cheng ◽  
Chris Venner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Population Based ◽  
First Line ◽  
Line Setting ◽  
The Impact

Background: We performed a retrospective population-based studyto assess the impact of tyrosine kinase inhibitors (TKIs) on overallsurvival (OS) in patients treated for metastatic renal cell carcinoma(mRCC) in Alberta, Canada and to assess the impact of nephrectomyon OS in patients treated with TKIs.Methods: We identified 134 patients who began taking a TKIbetween December 2003 and June 2007 for mRCC in Alberta. Wecompared survival in this group to that in an earlier cohort of141 pa tients treated with interferon-α (IFN-α) between May 1995and March 2003. We used the Kaplan–Meier method to determineOS, and we used a Cox proportional hazards model to determinehazard ratios (HRs) and confidence intervals (CIs). We performedmultivariate analysis to assess the impact of neprhectomy on OS.Results: Of the 134 patients treated with TKIs, 81 received treatmentin the first-line setting, whereas 53 received treatment after priorIFN-α therapy. All 141 patients from the IFN-α cohort receivedtreatment in the first-line setting. Patients treated with TKIs had animproved OS compared with the IFN-α cohort (HR 0.61, 95% CI0.45–0.83, p = 0.001). The median OS was 18 months in the TKIgroup and 10 months in the IFN-α group. The benefit of TKIs wasconfined to favourable and intermediate risk groups according tothe Memorial Sloan-Kettering Cancer Center prognostic model.Prior nephrectomy was associated with improved OS in the TKIcohort, independent of other prognostic factors.Conclusion: Tyrosine kinase inhibitors improve OS compared withIFN-α in mRCC. In patients treated with TKIs, prior nephrectomyis associated with improved survival independent of other prognosticvariables.Contexte : Une étude rétrospective de population a été menée afind’évaluer l’effet des inhibiteurs de la tyrosine-kinase (ITK) sur lasurvie globale (SG) des patients atteints d’un néphrocarcinomemétastatique et d’évaluer l’impact d’une néphrectomie sur la SGdes patients traités par ITK.Méthodes : Cent trente-quatre patients en Alberta ont entrepris untraitement par ITK entre decembre 2003 et juin 2007 en raisond’un néphrocarcinome. On a comparé les taux de survie dans cegroupe avec ceux d’un groupe de 141 patients ayant entrepris untraitement de première intention par IFN-α entre mai 1995 et mars2003. La survie globale a été calculée à l’aide de la méthode deKaplan Meier, et le risque relatif (RR) et les intervalles de confiance(IC) ont été calculés à l’aide du modèle des risques proportionnelsde Cox. Une analyse multivariée a permis d’évaluer l’impact dela néphrectomie sur la SG dans la population globale de l’étuded’une part et chez les patients traités par ITK d’autre part.Résultats : Les 134 patients ayant entrepris un traitement par ITK ontété répartis ainsi : traitement de première intention, 81 patients, ettraitement de seconde intention après un traitement par IFN-α,53 patients. Les patients traités par ITK ont montré une SG supérieurepar rapport aux patients traités par IFN-α (RR 0,61, IC à 95 % 0,45–0,83, p = 0,001). La SG médiane était de 18 mois chez les patientstraités par ITK et de 10 mois chez les patients traités par IFN-α. Letraitement par ITK n’a eu un avantage que chez les patients atteintsde néphrocarcinome métastatique présentant un risque faible ouintermédiaire selon le modèle du Memorial Sloan-Kettering CancerCener. Une néphrectomie antérieure a été associée à une meilleureSG dans la cohorte traitée par ITK, indépendamment des autres facteurspronostics.Conclusion : Le traitement par ITK a amélioré la SG par rapport autraitement par IFN-α dans une population « réelle ». Une néphrectomieantérieure a été associée à une SG supérieure chez lespatients traités par ITK.

scholarly journals Management of hepatocellular carcinoma after progression on first-line systemic treatment: defining the optimal sequencing strategy in second line and beyond

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
C.P. Amaro ◽  
V.C. Tam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Treatment Algorithm ◽  
Current Data ◽  
Second Line ◽  
First Line ◽  
Optimal Sequencing ◽  
The World ◽  
Sequencing Strategy ◽  
Line Setting

    Hepatocellular carcinoma (hcc) is one of the most common cancers in the world. It has a high mortality rate, espe­cially when localized treatments fail. For about a decade, the only systemic treatment shown to improve survival was sorafenib. Recently, lenvatinib was found to be noninferior to sorafenib for overall survival and the combination atezolizumab–bevacizumab improved survival compared with sorafenib. Similarly, in the post-sorafenib setting, a number of recent positive clinical trials have been reported, and they indicate that regorafenib, cabozantinib, and ramucirumab are effective and safe in the second-line setting.     With so many new options available, including immunotherapy, it is challenging to define the best sequence of systemic treatment for patients with hcc. In the present review, we introduce the current data for second-line sys­temic treatment and beyond in hcc. A treatment algorithm is also suggested, based on the best available evidence and expert opinion.

scholarly journals Combination of pembrolizumab and axitinib: a new gold standard in the first-line therapy for metastatic clear-cell renal-cell carcinoma?

2020 ◽  
Vol 16 (3) ◽  
pp. 29-37
Author(s):  
R. A. Gafanov ◽  
A. G. Dzidzaria ◽  
I. B. Kravtsov ◽  
S. V. Fastovets
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Clinical Results ◽  
First Line ◽  
Cell Renal Cell Carcinoma

The treatment strategy for metastatic renal cell carcinoma (mRCC) has evolved with the emergence of anti-angiogenic drugs, in particular tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs). Both treatment options improved patient outcomes and altered the natural history of mRCC. Clinical studies have focused on evaluating combination regimens containing ICI and VEGFR-targeted TKIs. The combination of axitinib with pembrolizumab (KEYNOTE-426) showed better results compared to sunitinib in patients with mRCC who had not previously received systemic therapy. In this article, we discuss the rationale for the combination of ICI and TKI based on preclinical data, as well as the clinical results obtained with the combination of axitinib with pembrolizumab in first-line patients in clinical trials.

The evolution of debulking nephrectomy and patient characteristics in metastatic renal cell cancer patients enrolled into first-line tyrosine kinase inhibitors clinical trials.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 513-513
Author(s):  
Avishay Sella ◽  
Kongming Wang ◽  
Tal Sella
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Phase I ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Phase Iii ◽  
Cytokine Therapy ◽  
First Line ◽  
Group 2

513 Background: The introduction of tyrosine kinase inhibitors (TKIs) revolutionized treatment of metastatic renal cell cancer (mRCC). The role of debulking nephrectomy (DN) still remains unresolved. We reviewed the rate of DN and characteristics of patients enrolled in prospective clinical trials with TKIs through and after 2007 (Motzer, N Engl J Med, 2007). Methods: PubMed, Cochrane library, ASCO and ESMO web sites were searched for phase I-III clinical trials with at least 15 patients of first line TKIs administered alone/combination for mRCC. Expanded access/randomized discontinuation trials were excluded. We used PRISMA guidelines for data collection. All trials included histology, DN, prior cytokine therapy and efficacy data. Trials missing either performance status (PS) or MSKCC criteria data were included. We reviewed 72 trials; 42 trials are included: Group 1: 22 (phase I/II-19, phase III-3) trials completed through 2007 with 2,355 patients, Group 2: 20 trials (phase I/II-17, phase III-3) completed after 2007 with 3,719 patients. Thirty trials with 1,055 patients, all phase I/II, were excluded. Group characteristics were compared using a Pearson Chi-square test at a 2-sided significance level of 0.05, median progression free survival (PFS) with available 95% CI were compared using weighted T-Test. Results: Group 2 had statistically significantly (p<0.001) less DN (85.7% vs 93.7%), less prior cytokine therapy (11.7% vs 46.8%), more poor prognosis (9.8% vs 4.0%), and intermediate prognosis characteristics (56.0% vs 51.9%), more PS 2 (2.8% vs 0.8%), and a similar rate of clear cell histology (97.9% vs 97.2%, p=0.097). Clinical objective response per intent to treat analysis was higher in Group 2 (28.6% vs 23.1%, p<0.001) with similar clinical benefit (73.2% vs 75.3%, p=0.074) and comparable PFS (median 9 vs 8.2 months, p = 0.2528). Conclusions: The use of debulking nephrectomy in patients participating in clinical trials has declined in the TKIs era. More patients with worse prognostic parameters participated in TKI trials after 2007. The reduction in prior cytokine therapy prevents estimation of these changes on TKI efficacy.

Real world experience of immuno-oncology agents in metastatic renal cell carcinoma: Results from the IMDC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 492-492 ◽  
Author(s):  
Steven Yip ◽  
Connor Wells ◽  
Raphael Brandao Moreira ◽  
Alex Wong ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Real World ◽  
Survival Data ◽  
Renal Cell ◽  
Treatment Duration ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Response Rates ◽  
Line Treatment ◽  
Second Line ◽  
Poor Risk

492 Background: Immuno-oncology (IO) checkpoint inhibitors have demonstrated efficacy in metastatic renal cell cancer (mRCC) treatment. Real world data is required to assess outcomes when applied to the general population. Methods: A retrospective analysis was performed using the IMDC database. It included mRCC patients treated with IO agents, including atezolizumab (Atezo), avelumab, ipilimumab, nivolumab (Nivo), and pembrolizumab (Pembro). Some patients were treated with combination therapy with a targeted agent. Patients may have received IO therapy as first-, second-, third-, or fourth-line treatment. Overall survival (OS), treatment duration, and overall response rates (ORR) were calculated. Results: 255 patients with mRCC treated with IO therapy were included. The ORR to IO therapy in those patients who were evaluable was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line therapy). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median OS rates were not reached, 26.7 mo, and 12.1 mo, respectively (p<0.0001). Conclusions: Response rates to IO therapies appear to remain consistent no matter which line of therapy it is used in. Within second-line treatment, IMDC criteria appear to stratify patients appropriately into favorable, intermediate, and poor risk groups. Survival data are premature and will be updated. In contrast to Nivo clinical trial data, where median treatment duration was 5.5 mo, longer treatment length is observed in real world practice. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document