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.

Relative risk of hematological toxicities in patients with advanced renal cell carcinoma treated with upfront immune checkpoint inhibitors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 675-675
Author(s):  
Nusrat Jahan ◽  
Somedeb Ball ◽  
Miguel Quirch ◽  
Shabnam Rehman ◽  
Kyaw Zin Thein ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Relative Risk ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
First Line Treatment

675 Background: Sunitinib was the standard first-line treatment of advanced renal cell carcinoma (aRCC) for the past decade, but it has been associated with significant hematological toxicities. Immune checkpoint inhibitors (ICI) based regimens have become the new preferred treatment for aRCC in the first-line setting. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hematological toxicities associated with upfront use of ICI-based regimens for aRCC. Methods: We conducted a systematic search at PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first-line treatment of aRCC were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Four phase 3 RCTs, CheckMate 214, IMmotion151, JAVELIN Renal 101 and KEYNOTE-426, randomizing 3706 patients were included in the analysis of anemia and thrombocytopenia. CheckMate 214 did not report the number of neutropenia. Hence, other 3 RCTs that included 2624 patients were analyzed for neutropenia. Following regimens were used in the study arms — CheckMate 214: nivolumab+ipilimumab, IMmotion151: atezolizumab+bevacizumab, JAVELIN Renal 101: axitinib+avelumab; and KEYNOTE-426: axitinib+ pembrolizumab. Sunitinib was used in the control arms for all the studies. The pooled RR of any-grade hematological toxicities are as follows — anemia: 0.31 (95% CI:0.24-0.41, P< 0.00001, I2=39%); thrombocytopenia: 0.11 (95% CI: 0.06-0.19, P<0.00001, I2=63%); neutropenia: 0.08 (95% CI: 0.05-0.13, P<0.00001, I2=0%). The pooled RR of grade 3 and higher hematological toxicities are as follows — anemia: 0.14 (95% CI:0.08-0.25, P< 0.00001, I2=0); thrombocytopenia: 0.06 (95% CI:0.02-0.16, P<0.00001, I2=4%); neutropenia: 0.06 (95% CI: 0.02-0.16, P<0.00001, I2=0%). Conclusions: ICI-based regimens have significantly reduced risk of any-grade as well as high-grade hematological toxicities compared to sunitinib in patients with aRCC.

Sunitinib scheduling in metastatic renal cell cancer: A single-center experience.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 554-554
Author(s):  
Sarah Louise Picardo ◽  
Dearbhaile Collins ◽  
Amnah Al Khamis ◽  
Victoria Teresa Mallett ◽  
Niamh M. Keegan ◽  
...  
Keyword(s):  
Side Effects ◽  
Renal Cell ◽  
Cell Cancer ◽  
Dose Intensity ◽  
Cancer Center ◽  
Line Treatment ◽  
First Line ◽  
Prognostic Variables ◽  
Dose Modifications ◽  
First Line Treatment

554 Background: Sunitinib is a receptor tyrosine kinase inhibitor that has proven activity as first line treatment for metastatic renal cell carcinoma (mRCC). The recommended dose is 50mg once daily in a 4 week on 2 week off schedule. However this regimen has a significant side effect profile and alternative schedules have been used to minimize dose reductions and maintain dose intensity. We sought to identify the incidence of dose modifications and assess toxicity in patients treated with two sunitinib schedules in a National Cancer Center. Methods: Patients with mRCC who had sunitinib as first line treatment were identified retrospectively and patient data reviewed. Two patient groups were identified: those who received sunitinib 50mg day 1-28 in 6 week cycles (cohort 1) and those who received sunitinib 50mg day 1-14 in 3 week cycles (cohort 2). Primary end point was incidence of dose modification. Secondary end points included incidence of common sunitinib-related side effects. Known prognostic variables, including prior nephrectomy, body mass index (BMI) and use of angiotensin system inhibitors (ASI) were correlated with time to disease progression (TTP). Results: Between 2009 and 2014, 28 patients were identified. Of those, 23 (83%) patients were treated in cohort 1, and 5 (17%) patients in cohort 2. Dose modifications were required in 13 (56.5%) patients in cohort 1, but only 2 (40%) patients in cohort 2. Common sunitinib-related side effects in cohort 1 included hypertension in 19 (79%), weight loss in 10 (41.6%), fatigue in 9 (37.5%) and nausea in 8 (33.3%) patients respectively. Overall, the use of ASIs correlated significantly with longer median TTP (10.5 months) compared to non-users (4 months) (p = 0.04). BMI ≥ 25 (TTP 9 vs. 3 months, p = 0.008) demonstrated a similar correlation. However, no difference in median TTP was noted between patients who had prior nephrectomy compared to those who had not (5 vs. 4 months) (p = 0.18). Conclusions: In this small retrospective study, standard sunitinib scheduling was associated with a high incidence of dose modifications and side-effects. Consistent with previous studies, we identified known prognostic variables. The use of sunitinib 50mg day 1-14 in 3 week cycles may be more tolerable for patients.

Relative risk of pneumonitis associated with first-line use of immune checkpoint inhibitors in advanced renal cell carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 676-676
Author(s):  
Nusrat Jahan ◽  
Francis Mogollon-Duffo ◽  
Srikala Meda ◽  
Fred L. Hardwicke ◽  
Lukman Aderoju Tijani
Keyword(s):  
Renal Cell Carcinoma ◽  
Relative Risk ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
First Line Treatment

676 Background: After approval in 2006, sunitinib remained the standard for the first line treatment of advanced renal cell carcinoma (aRCC) for a decade. Immune checkpoint inhibitors (ICI) have changed the landscape of aRCC management in recent years. Pneumonitis is a significant immune related adverse event (iRAE) associated with ICIs causing morbidity, mortality and treatment interruption. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis associated with first line use of ICIs for aRCCs. Methods: We conducted a systematic search using PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first line treatment of aRCC and reporting the number of pneumonitis for both intervention and control arms were included in the analysis. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Three phase 3 RCTs, CheckMate 214, IMmotion151 and KEYNOTE-426, randomizing 2833 patients (1427 in the ICI arms and 1406 in the control arms) were included in the analysis. ICI regimens used in the study arms were as follows — CheckMate 214: nivolumab and ipilimumab, IMmotion151: atezolizumab and bevacizumab, and KEYNOTE-426: pembrolizumab and axitinib. Sunitinib was used for all the control arms. Randomization was 1:1 in all three studies. Pneumonitis of any-grade was reported in 56 (3.92%) patients in the ICI arms versus 1 (0.07%) patient in the control arms. The pooled RR of any grade pneumonitis was 22.11 (95% CI: 5.34-91.55, P<0.0001, I2=0%). Grade 3 and above pneumonitis was reported in 12 (0.84%) patients in the ICI arms versus 0 (0%) patient in the control arms with pooled RR of 8.39 (95% CI: 1.54-45.80, P=0.01, I2=0%). Conclusions: The relative risk of any-grade as well as high-grade pneumonitis are significantly higher with ICI based regimens compared to sunitinib for aRCC. Early detection and prompt intervention are vital to reduce morbidy and mortality associated with this iRAE.

Determinants of treatment for first-line immune-based combinations in metastatic renal cell carcinoma: a critical overview of recent evidence

Immunotherapy ◽  
2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
Veronica Mollica ◽  
Francesco Massari
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
Critical Overview ◽  
First Line Treatment

The last three decades have witnessed a revolution in the therapeutic scenario of metastatic renal cell carcinoma (mRCC), due to the advent of novel agents including tyrosine kinase inhibitors, immune checkpoint inhibitors and the combination of both treatments. These strategies have reported unprecedented response rates, thus improving the clinical outcomes of mRCC patients, and current international guidelines support the use of immune-based combinations as first-line treatment in patients with metastatic disease. However, more data are awaited to help clinicians in the decision-making process. Herein, we provide an overview of recently published results regarding immune-based combinations as first-line treatment in mRCC patients, critically discussing available data that could help in suggesting determinants of treatment in this setting.

scholarly journals Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Anwen Xiong ◽  
Jiali Wang ◽  
Caicun Zhou
Keyword(s):  
Lung Cancer ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chinese Patients ◽  
Current Status ◽  
Line Treatment ◽  
First Line ◽  
Future Directions ◽  
First Line Treatment

Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%–85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.

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