1. Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
2. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
3. Medical Oncology, Gustave Roussy, Villejuif, France.
4. Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Health System, Los Angeles, CA

ABSTRACT

The treatment landscape of advanced renal cell carcinoma (aRCC) has witnessed significant benefits from the introduction of VEGF TKI/ICI (vascular endothelial growth factor receptor tyrosine kinase inhibitor/immune checkpoint inhibitor) combination in the first-line treatment. Such outcome benefits could extend to the relapsed/refractory setting with an effective, well-tolerated novel combination. Since the U.S. FDA approval of tivozanib monotherapy for the treatment of adult patients with relapsed or refractory advanced RCC following two or more prior systemic therapies,¹ there is growing interest in exploring its full potential in combination with anti-PD-1 like ICI agents. In this roundtable discussion, internationally renowned cancer experts brainstorm the potential immunomodulatory capabilities of tivozanib plus nivolumab combination as first-liane and beyond settings in patients with metastatic RCC. The expert panel also explore potential data from previous and ongoing clinical trials and shared their perspectives about a tolerable safety profile and promising antitumor efficacy

Webinar Transcript

INTRODUCTION

In recent years, tyrosine kinase inhibitor/immune checkpoint inhibitor/ (ICI/TKI) combination regimens have emerged as novel treatment options for metastatic renal cell carcinoma (mRCC). However, it remains unclear how such combinations fit into the larger landscape of mRCC management, both in the first-line and beyond. Moreover, several clinical trials exploring such combinations have largely focused on the treatment-naïve population and their efficacy and toxicity beyond the first-line settings remain poorly defined.

Tivozanib, a highly selective and potent VEGF TKI, has demonstrated single-agent efficacy in advanced renal cell carcinoma.^2,3 In addition, Tivozanib exhibits minimal off-target toxicities and a favorable adverse event (AE) profile.^2-5 Based on these data, Tivozanib monotherapy was approved by the FDA on March 10th, 2021 for the treatment of adult patients with relapsed or refractory advanced RCC who have received 2 or more prior systemic therapies.¹ As such, TKI/ICI combination regimens represent rationally designed novel therapeutic combinations built upon earlier work showing individual efficacy of each class of drugs in RCC. Tivozanib and nivolumab are ideal candidates for combination therapy owing to their efficacy, safety profile and a synergy between VEGFR and programmed death-1 (PD-1) inhibition in RCC.⁶ Tivozanib therapy facilitates immune-mediated responses through decrease in regulatory T cells (Tregs).^7,8 The selectivity and favorable tolerability of the VEGFR TKI tivozanib⁹ may allow it to be used more readily as a combination therapy with an immune checkpoint inhibitor (ICI). Nivolumab an anti-PD-1 monoclonal antibody blocks the immune checkpoint protein PD-1 from interacting with its ligands programmed death ligands (PD-L1 and PD-L2). These mechanisms may act synergistically to potentially enhance the immune response that mediates antitumor activity.⁴

Following the FDA approval of tivozanib in renal cell carcinoma, tivozanib was explored in combination with the PD-1 inhibitor nivolumab in the Phase 1/2 TiNivo study,6 where it demonstrated favorable tolerability and prolonged PFS using the combination of tivozanib and nivolumab in both treatment naïve and previously treated patients with advanced RCC. Currently, the TiNivo-2 trial (NCT04987203)10 is exploring immunomodulatory effects and differentiated tolerability profile of the tivozanib plus nivolumab combination versus tivozanib monotherapy in a phase 3, randomized, controlled, multicenter, open-label study.¹⁰

The objective of this roundtable program is to further gain insights into the efficacy and tolerability of tivozanib plus nivolumab combination therapy for advance renal cell carcinoma patients. Also, leading oncology panelists share their insights that would enable clinicians to better understand full potential of tivozanib plus ICI combinations in a rapidly changing treatment paradigm of kidney cancers. The panel includes Drs. Robert Motzer, MD, Dr. Toni Choueiri and Dr. Laurence Albiges, MD and discussion was chaired by a renowned expert and our editor-in-chief, Robert A. Figlin, MD.
Below is an excerpt from the discussion edited for brevity and clarity.

ROUNDTABLE DISCUSSION

Dr. Figlin:

         Welcome everybody. This is Robert Figlin, the Steven Spielberg Family Chair in Hematology-Oncology, Professor of Medicine and Biomedical Sciences, and Deputy Director of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles. On behalf of the kidney cancer journal, I am delighted today to have a roundtable with some distinguished investigators with great experience in the utility of tivozanib and its combination strategies, both in the clinical and research setting. So let me welcome Dr. Robert Motzer, Dr. Toni Choueiri and Dr. Laurence Albiges. Please introduce yourself to the audience.
Dr. Motzer:

         I am an attending physician and Kidney Cancer Section Head in the Genitourinary Service, Department of Medicine, and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York.
Dr. Choueiri:

         I am the Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI), co-leader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center, and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.
Dr. Albiges:

         I am Laurence Albiges a medical oncologist. I am head of Medical oncology department at the Gustave Roussy Institute in France.
Dr. Figlin:

         You are distinguished group of panelists who join us today to discuss the roles of tivozanib. Dr. Motzer, let’s start with you. You are a pioneer in the development of tyrosine kinase inhibitors (TKI) and other potential therapeutics for the treatment of kidney cancers. Can you help us understand where tivozanib, a VEGF-TKI fits in that spectrum and the clinical trial that resulted in its approval in second line therapy patients that had received prior therapy?
Dr. Motzer:

         Tivozanib is a potent and highly selective VEGF receptor tyrosine kinase inhibitor. It was developed at a very exciting time with many advances in our therapeutic armentarium between 2005 and 2012. At that time, there were several different VEGF TKIs including sunitinib, sorafenib and pazopanib which were studied in phase 3 trials and some of which were approved. Outstanding attributes of tivozanib in addition to efficacy are its tolerability and lack of off-target toxicities that had been seen with some other approved TKIs like sorafenib. Tivozanib was studiedin a randomized phase III TiVo-1 trial compared to sorafenib in treatment naïve or prior cytokine-treated subjects with metastatic RCC (mRCC). Based on the improved progression free survival (PFS), tivozanib was approved in Europe for first-line treatment of mRCC. However due to conflicting OS results, approval was put on hold in the United States. Given the potential efficacy in later lines of therapy, TIVO-3 was designed as an open-label phase 3, randomized, controlled, multicenter study to compare tivozanib to sorafenib in 350 subjects with refractory advanced renal cell carcinoma. The patients were heavily pretreated patients had two or three prior treatments, including a TKI and including some patients who have progressed on checkpoint inhibitors.

      TIVO-3 met its primary endpoint by showing improvement in progression free survival compared to sorafenib among favorable and intermediate IMDC risk patients, indicating ongoing responsiveness to VEGFR inhibition . In the heavily pretreated population, tivozanib arm had a favorable safety profile which is a hallmark of tivozanib with fewer grade three or four adverse events, particularly those that are most troublesome to patients including hand foot syndrome and fatigue. The issue around overall survival was resolved, with both arms showing similar overall survival, and the tivozanib arm having superior response rate and progression free survival.
Dr. Figlin:

         Toni, let me turn to you. You are a leader of combination therapies that have transformed the kidney cancer landscape in recent years. Can you help us understand the preclinical biological mechanism when combining a TKI with an IO? Do they become additive or synergistic? Are thereeffects on the tumor microenvironment that make those combinations better than either of those drugs alone?
Dr. Choueiri:

         I can tell you that beyond seeing if there’s a synergy or additive effect, we are combining two drugs endowed with single agent activity of their own in frontline as well as refractory setting. Based on the clinical data, we cannot confirm that if there has been synergy or if each drug works on its own. Having said so, we know that in preclinical models, T cell mediated cancer cell killing, which is how immune checkpoint inhibitor largely works, may be enhanced through a reversal of VEGF mediated immunosuppression and other multiple steps in the immunity cycle. For example, the promotion of T cell priming and activation through the maturation of dendritic cells can happen by inhibiting VEGF. In addition, inhibiting VEGF can lead to the normalization of the tumor vasculature so that T cells could infiltrate the tumor better. VEGF inhibition can also lead to an immune permissive tumor microenvironment by decreasing the Myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells.
Dr. Figlin:

         That’s quite a nice summary Toni! thank you. So Laurence let me let me turn to you. You’re the first author on the TiNivo-2 trial. It’s the Phase 1/2b trials that you’ve reported. So dive into that trial in terms of what you was the patient populations that you studied, the outcomes that you observed, and why that pivotal early trial has led to a larger trial in the phase III setting.
Dr. Albiges:

         It’s actually building on two previous developments from Drs. Motzer and Choueiri based on the survival benefits obtained from single agent activities from both potent VEGF-TKI and immune checkpoint inhibitor and also as Dr. Choueiri highlighted that there is also an immunological standpoint as well. Based on such rational and also because of other combinations that were similarly developed, we launched an open-label, multicenter study of tivozanib in combination with nivolumab in patients with metastatic RCC (NCT03136627). In this study, patients initially received tivozanib 1.0 mg once daily for 21 days of treatment followed by 7 days off treatment. A standard dose of Nivolumab (240 mg) was administered as an infusion every 2 weeks starting on day 1 of cycle 1, and again on day 15. Overall, 25 patients have been treated as part of this phase I. patients with advanced RCC who received tivozanib plus nivolumab demonstrated a tolerable safety profile with minimal off-target effects when used as first-line and beyond treatment in patients with advanced RCC.

       We assessed that 80% of our patient had some degree of remission, and the disease control rate was 96%. So overall, we were able to achieve a response rate of 56% in patients who received the tivozanib. Ultimately, the early signs of progression free survival was very enthusiastic with a median PFS of 18.9 months. So clearly, we observed a great signal of activity. What I can tell you from a clinical standpoint is that the tolerability was great, thanks to potency of tivozanib. The most frequent treatment-related toxicity was hypertension that was consistent with toxicity profiles of both drugs. Therefore it does require a close monitoring. However, as medical oncologists in the field of RCC had been exposed to hypertension for many years, hypertension was manageable from a clinical standpoint. The adverse events are comparable with other VEGFR TKI-PD-(L) and generally tolerable in combination setting.
Dr. Figlin:

         Albiges Do you have any follow up data in terms of durable responses in those 25 patients that you’ve observed in your clinic?
Dr. Albiges:

         The answer is yes. I could not speak for the entire study as it was a multi-centric study in France. However, I can tell you that I had seen very long, sustained response in my hospital. In some patients, we were able to discuss treatment discontinuation. So clearly what we’re seeing is a great disease control during the follow-up.
Dr. Figlin:

         Before we turn to Toni and talk about the phase III trial. I think it’s important that we circle back and talk about quality of life benefits of tivozanib. Dr. Motzer, I know that you’ve reported on Quality of life data and the safety profile of tivozanib in the clinical setting. Please summarize some key objective data that you’ve reported on.
Dr. Motzer:

         We performed quality of life analysis from the TiVo-1 trial, also accounting for efficacy and adverse event profile. In that direct comparison to serofenib, tivozanib was associated with a significant improvement in PFS and a favorable quality of life profile when administered to patients with metastatic RCC. In fact the toleratibility and safety profile is one of the greatest attributes of tivozanib. Tivozanib resulted in lower rates of certain side effects that are associated with the a decline in quality of life, including hand-foot skin reaction, rash anddiarrhea. There were fewer dose reductions and interruptions for tivozanib compared with sorafenib. In the other hand, tivozanib was characterized by higher rates of hypertension and dysphonia, but it was generally well tolerated.
Dr. Figlin:

         Dr. Choueiri, let me get back to you. As a first author of TiNivo-2 study, please help us understand where you think that trial fits, what the goals and objectives are, and how that might offer our patients some continued immune modulation with positive outcomes in patients with mRCC?
Dr. Choueiri:

         First, we were essentially looking into the unmet need in advanced RCC. One of the unmet needs is treatment for those patients whose tumors progressed after prior immune checkpoint inhibitors That’s why we launched TiNivo-2 study in this population based on the quite encouraging data from a phase 1/2b study that Dr. Albiges just mentioned. In TiNivo-2 trial, patients will be randomized to tivozanib monotherapy as the standard and the experimental arm have the combination of tivozanib plus Nivolumab. Patients should have been progressed at least one prior r line of therapy including an immune checkpoint inhibitor.. Subjects will be stratified by IMDC risk category and whether ICI was received in most recent line of treatment or not. Subjects will receive Tivozanib (1.34 mg orally once daily) for 21 consecutive days followed by 7 days off. In the combination arm, subjects will also receive Nivolumab 480mg intravenously every 4 weeks. The dose of tivozanib will be comparatively lower when delivered in combination with nivolumab as compared to tivozanib monotherapy. Ultimately, our goal here is to find a niche of completely unmet need and see if adding nivolumab on a backbone of VEGF TKI of tivozanib would result in improved outcomes in terms of progression-free survival (PFS) in patients with renal cell carcinoma who have progressed following 1-2 lines of therapy including an immune checkpoint inhibitor.
Dr. Figlin:

         We all recognize that you’re to be congratulated along with Drs. Motzer, Dr. Albiges and other colleagues who are part of that study for addressing the critical unmet need. So let me just go around the table and ask each of you. We have accomplished so much in kidney cancer during the last two decades, through the era of the tyrosine kinase inhibitors and currently through the era of the immune checkpoint inhibitors and their combination strategies. I know that many of us are looking at triplets that we would never have thought about it in kidney cancer a couple of decades ago. Here we’re trying to combine it with agents such as HIF2a inhibitors for example. Where do you see us going from here Dr. Motzer? So how do you see the field evolving?
Dr. Motzer:

         Theidentification of new agents with a novel mechanism of action is critical. One new class of drugs which Dr. Choueiri has been pivotal in terms of bringing forward are the HIF2a inhibitors. As a class these drugs are active and seem to be very well tolerated and combine well with other agents. In one s study with hypoxia-inducible factor 2α (HIF-2α) belzutifan plus cabozantinib, the preliminary results showed good antitumor activity and tolerability for the combination. Given the positive outcomes from tivozanib combination studies, as a next step I’d like to see one of the HIf2a inhibitors added to tivozanib and nivolumab as a first-line therapy. I’m even an advocate for a study of tivozanib plus nivolumab combination in the adjuvant setting. I recognize that TKIs as single agent certainly didn’t pan out in the adjuvant setting because of poor tolerability. However, tivozanib may have a better chance particularly in combination with a checkpoint inhibitor in the adjuvant setting. Lastly, we need a better understanding of underlying biology to see if we can identify patient subpopulation that will respond best to such combination settings.
Dr. Figlin:

         Dr. Choueiri, without putting you on the spot, but putting you on the spot. You’ve articulated nicely an increasing role of IO-TKI as a second line after prior IO therapy in the high risk resected population. How do you think the field is going to evolve if there’s an increased uptake of immune checkpoint inhibition in the high risk resected population?
Dr. Choueiri:

         Absolutely, this is why we need studies in the post IO setting. In TiNivo-2 which we are talking about, we may include a subgroup to assess outcomes in the prior adjuvant IO setting. I tend to believe it will not be different if patients progressed within a year after therapy. But it will be different biology if progression happens after a year. If this strategy is successful, then we have to look at that we have a drug approved with the same construct as the design of TiNivo-2, but strictly in the adjuvant setting. And that’s something we’ve been working on because what if the biology is different.
Dr. Figlin:

         Absolutely. Dr. Albiges, one of the challenges is we still have to navigate through patients with brain metastases and bone metastases. Any insights on whether there are now evolving populations of patients that we need to be address because of unmet needs?
Dr. Albiges:

         I agree with you that there is an unmet need in those patients with brain and/or bone metastasis and obviously, we need to think about those patients that are difficult to treat. Now, we know the role of multimodal approach combining stereotactic radiation therapy on top of our systemic treatment and maybe defining the optimal systemic treatment. it’s likely that we may want to combine VEGF-TKI with an immune checkpoint inhibitors so that we would be able to induce more tumor shrinkage in those subset of population. In addition to subset of patient with metastasis, there is also other tumor types such as non-clear cell renal cell carcinoma and other different tumor entities. For those, we clearly need to have more clinical trials being developed and test some of those combinations in such patient populations that usually have very aggressive features. So beyond clear cell RCC, there are challenges from different pathological, and specific tumors that need to be addressed. I really feel that we have made a long way but we still have a lot to go and especially with how to sequence those different agents and work on the rescue strategy.
Dr. Figlin:

         Let me just summarize by saying that our distinguished colleagues have shared their insights regarding the survival benefits, tolerance profile, quality of life and the rationale for combining tivozanib with immunotherapy along with some key perspectives about prospective pivotal trials for both adjuvant as well as systemic therapeutic settings. I would like to thank Drs. Motzer, Choueiri and Albiges for joining with us for this stimulating roundtable discussion.

CONCLUDING REMARKS

An unmet need remains for developing novel therapeutic combination that produces effective, durable responses without adding substantial toxicity in patients with relapsed or refractory advanced RCC. Anti-angiogenic therapy in combination with ICIs in the first-line setting has demonstrated not only favorafble efficacy, but also improved tolerability in patients with advanced RCC. For example, tivozanib plus tivozanib combination demonstrated a promising safety and efficacy profile with minimal off-target effects as first-line and beyond treatment in patients with advanced RCC. In this roundtable discussion, renowned experts convened to examine the immunomodulatory potential of tivozanib and also its synergistic potential when combined with nivolumab as a treatment option in patients with treatment-naïve or previously treated metastatic RCC. Also, panelists shared their perspectives about the recent TIVO-3 and ongoing TiNivo-2 trial with regards to safety and efficacy.

CONFLICT OF INTERESTS

RJM reports consulting fees from Aveo, Calithera, Eisai, Eli Lilly, EMD Serono, Genentech, Merck, Novartis AG, Pfizer, and Roche, and contracted research to employer MSKCC for Bristol Myers Squibb, Eisai, Exelixis, Genentech, Merck, Pfizer, and Roche. TKC reports grants received from Pfizer during the conduct of the study; personal fees received from Agensys, Alexion, Alligent, American Society of Clinical Oncology, Analysis Group, AstraZeneca, Bayer, Bristol Myers Squibb, Celldex, Cerulean, Clinical Care Options, Corvus, Dana-Farber Cancer Institute, EMD Serono, Inc., Eisai, Exelixis, Foundation Medicine, Genentech/Roche, GSK, Harborside Press, Heron, Ipsen, Kidney Cancer Association, Kidney Cancer Journal, Lpath, Lancet Oncology, Lilly, Merck & Co., Michael J. Hennessy Associates, National Comprehensive Cancer Network, Navinata Health, New England Journal of Medicine, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus Laboratories, Sanofi, Seattle Genetics/Astellas, and UpToDate outside the conduct of the study; grants received from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Cerulean, Corvus, Eisai, Exelixis, Foundation Medicine, Genentech/Roche, GSK, Ipsen, Merck & Co., Novartis, Peloton Therapeutics, Pfizer, Prometheus Laboratories, Takeda, and TRACON outside the conduct of the study; and medical writing and editorial assistance provided by ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, and Parexel, funded by pharmaceutical companies. LA reports consulting fees compensated to their institution from Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Corvus Pharmaceuticals, Exelixis, Ipsen, Merck KGaA, Merck & Co., Novartis, Peloton Therapeutics, Roche, and Pfizer outside the submitted work. HM has declared no conflicts of interest. RAF: No relevant conflicts to report for this roundtable.

CONTRIBUTIONS

The roundtable panelists (authors) were invited to participate in this discussion by the journal. All authors listed in the manuscript contributed significantly to KCJ roundtable. All authors have read and approved the final version. The final content and article is the sole work of the authors.

ACKNOWLEDGMENTS

This educational roundtable program is supported byAVEO Oncology

For further information about TiNivo-2 study:TiNivo-2 clinical study

KEYWORDS:

Tivozanib, vascular endothelial growth factor receptor, tyrosine kinase inhibitor, nivolumab, immune checkpoint inhibitor, renal cell carcinoma, kidney cancer.

REFERENCES

• 1. FDA approves tivozanib for relapsed or refractory advanced renal cell carcinoma. Drug Approvals and Database 2021 (March 10, 2021). https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma.
• 2. Motzer RJ, Nosov D, Eisen T et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013; 31: 3791-3799.
• 3. Rini BI, Pal SK, Escudier BJ et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020; 21: 95-104.
• 4. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.
• 5. Pal SK, McDermott DF, Escudier et al. TIVO-3: Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the phase 3 TIVO-3 study of relapsed or refractory mRCC. Presented at: 2021 ASCO Virtual Program; May 27, 2021. Abstract 4567.
• 6. Albiges L, Barthélémy P, M Gross-Goupil M, Negrier S, Needle MN, Escudier B. TiNivo: Safety and Effi cacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma. Ann. Oncol. 2021. 32(1), 97-102.
• 7. Voron T, Colussi O, Marcheteau E et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015; 212: 139-148.
• 8. Pawlowski N, et al. Impact of various first- and second-generation tyrosine-kinase inhibitors on frequency and functionality of immune cells. Cancer Res. 2013;73. Abstract 3971.
• 9. Winston W et al. Tivozanib, a selective VEGFR TKI, potently blocks angiogenesis and growth in tumors that express a high level of VEGF-C and are refractory to VEGF-A blockade. AACR–NCI–EORTC International Conference: Molecular Targets and Cancer Therapeutics; San Francisco, CA; November 12–16, 2011.
• 10. Choueiri TK, Albiges L, Hammers HJ, McKay RR, Heng DYC, Beckermann K, Kasturi V, and Motzer RJ. TiNivo-2: A phase 3, randomized, controlled, multicenter, open-label study to compare tivozanib in combination with nivolumab to tivozanib monotherapy in subjects with renal cell carcinoma who have progressed following one or two lines of therapy where one line has an immune checkpoint inhibitor. Journal of Clinical Oncology 2022 40:6_suppl, TPS405-TPS405.
• 11. Molina AM, Hutson TE, Nosov D, Tomczak P, Lipatov O, Sternberg CN, Motzer R, Eisen T. Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study. Eur J Cancer. 2018 May;94:87-94. doi: 10.1016/j.ejca.2018.02.009. Epub 2018 Mar 20. PMID: 29547835; PMCID: PMC6774240.
• 12. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803-1813. doi:10.1056/NEJMoa1510665
• Correspondence to: Dr. Figlin,Robert.Figlin@cshs.org

The post Recent Advances in Tivozanib plus Nivolumab Combinatorial Strategies in Renal Cell Carcinoma first appeared on GUcancers.

August 20, 2021

Frontline Keytruda plus Lenvima for advanced renal cell carcinoma is an effective treatment with life-prolonging benefits, although patients should be monitored for side effects that can be easily managed.

• The FDA  approved a combination of Merck & Co. and Eisai drugs (Keytruda and Lenvima) that were shown in clinical testing to delay the progression of advanced kidney cancer and extend survival for patients when used as first-line therapy.
• Merck and Eisai view the combination as a way to give patients and doctors more weapons against cancer. Keytruda, an infusion, works by revving up the immune system. Lenvima, a capsule, works by targeting proteins on cancer cells that help tumors spread.

“It is a great time for the field of (renal cell carcinoma). What an honor and privilege to see these advances impacting the lives of patients. This combo did have though the longest (progression-free survival), and highest response rate and complete response rates as compared to other combinations, though not through a direct head-to-head comparison.” says Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston. “Keytruda plus Lenvima is another option,” Dr. Choueiri mentioned,

The latest approval was based on a three-arm study called CLEAR. which demonstrated a 61% reduced risk of disease progression or death in patients treated with the combination therapy. The regimen also contributed to a progression-free survival of 23.9 months compared with 9.3 months in patients treated with Sutent (sunitinib). The Keytruda-Lenvima group showed the biggest benefit. When compared with Sutent, the Keytruda-Lenvima combination treatment reduced the risk of death or disease progression by 61%. Patients on the two-drug therapy had a median of 23.9 months of progression-free survival, compared with 9.2 months for Sutent. Measured by overall survival, combination therapy reduced the risk of death by about a third compared to Sutent. Still, the drugs do have side effects. Adverse reactions caused 37% of patients in the Keytruda-Lenvima arm to stop taking one or both of the medications.

Merck won a priority review from the FDA for the drug combination based on benefits seen in the CLEAR study. At the time Merck inked its larger deal with Eisai in 2018, the combination had already received an FDA Breakthrough Therapy Designation for advanced kidney cancer, allowing the company to move faster through the development and review process.

The post Keytruda plus Lenvima Combo Received FDA Approval for Advanced Kidney Cancer first appeared on GUcancers.

Recent findings based on the phase 1b COSMIC-021 trial in  Journal of Clinical Oncology demonstrated that treatment with the multikinase inhibitor cabozantinib (Cabometyx) plus the immune checkpoint inhibitor atezolizumab (Tecentriq) showed promising efficacy in patients with both clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC), according to findings from the phase 1b COSMIC-021 trial.¹ The combination reached an objective response rate (ORR) as high as 58% across two ccRCC cohorts and an ORR of 31% in patients with nccRCC.

“Cabozantinib plus atezolizumab demonstrated encouraging clinical activity in patients with advanced RCC regardless of histology. The safety profile with the combination was tolerable with dose modification and comparable to previous reports,” first author Sumanta K. Pal, clinical professor, Department of Medical Oncology & Therapeutics Research; co-director, Kidney Cancer Program, City of Hope, and coinvestigators wrote.

The multicenter, open-label phase 1b COSMIC-021 trial (NCT03170960) enrolled 102 patients with advanced RCC. Patients with ccRCC received atezolizumab plus either 40 mg (n = 34) or 60 mg (n = 36) of cabozantinib. Patients with nccRCC (n = 32) received atezolizumab plus 40 mg of cabozantinib.

In the 40-mg cabozantinib ccRCC group, the median age was 68 (range, 39-87), 79% of patients were male, and 71% were White. The ECOG performance status was 0 for 79% of patients and 1 for 21% of patients. Regarding IMDC risk, 21% were favorable, 76% were intermediate, and 3% were poor. Twenty-six percent of the cohort had a sarcomatoid component, which was significantly higher than the other 2 study arms. The PD-L1 status by CPS was ≥1 for 26% of patients, <1 for 44% of patients, and unknown for 29% of patients. Fifty-three percent of patients had ≥3 tumor sites. Metastatic sites included lung (79%), lymph node (47%), liver (15%), and bone (12%). One patient had received prior systemic anticancer therapy, 3 patients had prior radiotherapy, and 85% of patients had prior nephrectomy.

In the 60-mg cabozantinib ccRCC group, the median age was 60 (range, 42-82), 72% of patients were male, and 94% were White. The ECOG performance status was 0 for 69% of patients and 1 for 31% of patients. Regarding IMDC risk, 39% were favorable, 58% were intermediate, and 3% were poor. Six percent of the cohort had a sarcomatoid component. The PD-L1 status by CPS was ≥1 for 22% of patients, <1 for 50% of patients, and unknown for 28% of patients. Thirty-nine percent of patients had ≥3 tumor sites. Metastatic sites included lung (75%), lymph node (42%), liver (8%), and bone (11%). One patient had received prior systemic anticancer therapy, 4 patients had prior radiotherapy, and 89% of patients had prior nephrectomy.

In the nccRCC group, the median age was 62 (range, 37–78), 81% of patients were male, and 72% were White. The ECOG performance status was 0 for 75% of patients and 1 for 25% of patients. Regarding IMDC risk, 38% were favorable, 47% were intermediate, and 16% were poor. Thirteen percent of the cohort had a sarcomatoid component. Regarding histology subtype, 47% were papillary, 28% were chromophobe, and 22% were others. The PD-L1 status by CPS was ≥1 for 13% of patients, <1 for 56% of patients, and unknown for 31% of patients. Fifty-six percent of patients had ≥3 tumor sites. Metastatic sites included lung (50%), lymph node (59%), liver (16%), and bone (16%). Seven patients had received prior systemic anticancer therapy, 2 patients had prior radiotherapy, and 69% of patients had prior nephrectomy.

The median follow-up for the 40-mg ccRCC arm was 25.8 months and the ORR was 53%, including a complete response (CR) rate of 3%. The median progression-free survival (PFS) was 19.5 months. In the 60-mg ccRCC arm, the median follow-up was 15.3 months and the ORR was 58%, including an CR of 11%. The median PFS was 15.1 months. Among patients with nccRCC, the ORR was 31%, comprising all partial responses. The median PFS was 9.5 months.

Regarding safety, grade 3/4 treatment-related adverse events (TRAEs) occurred in 71% and 67% of patients in the 40-mg and 60-mg ccRCC groups, respectively. TRAE-related discontinuation of both drugs occurred in 15% and 6% of these 2 arms, respectively. In the nccRCC arm, 38% of patients had grade 3/4 TRAEs and TRAEs led to discontinuation of both drugs in 3% of patients. No treatment-related death occurred in the trial.

“These results support further evaluation of cabozantinib plus atezolizumab in patients with advanced RCC in the phase III trial setting, including those with non–clear cell histology. Patients with non–clear cell RCC have limited treatment options, and prospective data on tyrosine kinase inhibitor plus immune checkpoint inhibitor combinations are lacking for this population,” the authors wrote.

Reference

1. Pal SK, McGregor B, Suárez C, et al. Cabozantinib in combination with atezolizumab for advanced renal cell carcinoma: results from the COSMIC-021 study [published online ahead of print September 7, 2021]. J Clin Oncol. doi: 10.1200/JCO.21.00939

The post Combo of cabozantinib plus atezolizumab active across kidney cancer subtypes first appeared on GUcancers.

August 16, 2021

FDA approves Merck’s Welireg for the treatment of adult patients with von Hippel-Lindau disease who require therapy for tumor growth.

FDA have approved the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan (Welireg, Merck) for the treatment of patients with some types of Von Hippel-Lindau (VHL) disease-associated tumors. The approval marks the first HIF-2α inhibitor therapy approved in the United States for some types of Von Hippel-Lindau disease-associated tumors.

FDA approval is based on results from the study 004 trial (NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor localized to the kidney.

The drug has been approved for adults with VHL disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery. It is the first HIF-2α inhibitor therapy approved in the United States, according to a press release from Merck.

VHL disease is estimated to occur in 1 of every 36,000 individuals. Patients with the disease are at risk for benign blood vessel tumors as well as some cancerous ones, such as RCC.

“VHL disease is a rare and serious condition,” said Eric Jonasch, MD, principal investigator of Study 004 and a professor at the University of Texas MD Anderson Cancer Center, in the press release. “Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors.”

The approval was based on data from Study 004, an open-label trial of 61 patients with VHL-associated RCC and at least 1 measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors and the study excluded patients with metastatic disease. Participants received belzutifan 120 mg once daily until progression of disease or unacceptable toxicity.

According to the press release, the median duration of exposure to belzutifan was 68 weeks. In patients with VHL-associated RCC, belzutifan recipients had an overall response rate (ORR) of 49% and all responses were partial responses. The median duration of response had not yet been reached and among responders, 56% were still responding after at least 12 months. The median time to response was 8 months.

In patients with VHL-associated pancreatic neuroendocrine tumors, belzutifan showed an ORR of 83%, with a complete response rate of 17% and a partial response rate of 67%. The median duration of response had not yet been reached and among responders, 50% were still responding after at least 12 months. The median time to response was 8 months.

“Welireg is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition,” said Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, in the press release.

Serious adverse events (AEs) occurred in 15% of patients who received belzutifan and included anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion. Permanent discontinuation due to AEs occurred in 3.3% of patients and included dizziness and opioid overdose.

Furthermore, dosage interruptions due to an AE occurred in 39% of patients and included fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions due to an AE occurred in 13% of patients and the most frequent reaction that required dose reduction was fatigue.

Finally, the most common AEs occurring in 25% or more of patients were hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

“The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,” said Ramaprasad Srinivasan, MD, PhD, head of the molecular cancer therapeutics section of the Urologic Oncology Branch at the National Cancer Institute, in the press release. “The FDA’s approval of Welireg marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors.”

REFERENCE

FDA Approves Merck’s Hypoxia-Inducible Factor-2 Alpha (HIF-2a) Inhibitor Welireg (belzutifan) for the Treatment of Patients With Certain Types of Von Hippel-Lindau (VHL) Disease-Associated Tumors. News release. Merck; August 13, 2021. Accessed August 16, 2021. https://www.merck.com/news/fda-approves-mercks-hypoxia-inducible-factor-2-alpha-hif-2%ce%b1-inhibitor-welireg-belzutifan-for-the-treatment-of-patients-with-certain-types-of-von-hippel-lindau-vhl-disease/

The post US FDA Approves Belzutifan for Tumors Associated With Certain Types of Von Hippel-Lindau Disease first appeared on GUcancers.

Ochsner Precision Cancer Therapies Program and Ochsner Cancer Institute, Benson Cancer Center. New Orleans LA

Correspondence to: Marc R. Matrana. Ochsner Precision Cancer Therapies Program and Ochsner Cancer Institute 1514 Jefferson Highway, New Orleans LA – 70121. E-mail: MaMatrana@ochsner

ABSTRACT

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The post ASCO21 Meeting Summary – Kidney Cancer first appeared on GUcancers.

Novel Drug Combinations Gain Traction Across Therapeutic Landscape

More than a year since the COVID-19 crisis upended the face of health care in the United States, its impact on cancer clinical trials has continuously been seismic. Right now, it seems likely to be a while before we enroll newly designed studies and start gathering trial data at the rate they once were. While there is only a limited capacity for bringing in new trials or launching new therapies into clinical practice, the oncology community certainly moved quickly with a concerted effort to get the halted cancer trials back up and running. This year’s ASCO Genitourinary Cancers Symposium sessions offered tantalizing preview of clinical breakthroughs and practice-changing research updates in GU cancers landscape despite the pandemic’s impact on clinical trials space worldwide.

As highlighted in the recent Kidney Cancer Journal online edition, GU ASCO21 abstracts provided snapshots of the most important trends, foremost research and key strategies from latest clinical trials that impact the current standard of care in renal cancer. Certainly, looming on the horizon are the new IO/IO and IO/TKI combinations, which generated a lot of buzz at this year’s ASCO in the renal cancer therapeutics space. Least to say, while targeted agents and immune monotherapies are still moving the needle to some extent, combination regimens comprised of IO/IO, IO/TKI, or other molecularly targeted agents are gaining momentum in evolving RCC landscape.

Let’s have a quick snapshot of the latest data from the GU21 sessions. In the pivotal phase 3 CLEAR study (KEYNOTE-581), lenvatinib plus pembrolizumab demonstrated statistically significant and clinically meaningful improvements in progression-free survival, overall survival and objective response rate versus sunitinib, supporting the regimen as a potential first-line treatment for advanced RCC. Also, improvement in ORR and PFS, but not OS was observed for lenvatinib at 2 different starting doses in combination with everolimus vs sunitinib. Other related abstract presented quality of life outcome data from a phase II trial of lenvatinib plus everolimus in patients with RCC. Investigation by Choueiri and colleagues was the first to report efficacy of combining the novel HIF-2alpha inhibitor plus cabozantinib (a VEGF TKI) in 118 patients with advanced clear-cell RCC. Belzutifan in combination with cabozantinib demonstrated promising antitumor activity and better tolerability in previously treated patients with metastatic ccRCC. CheckMate 9ER (NCT03141177), a phase III open-label trial has shown that nivolumab + cabozantinib demonstrated statistically significant HRQoL benefits and superior efficacy versus sunitinib. Also, nivolumab + cabozantinib demonstrated improved efficacy and prolonged survival vs sunitinib in previously untreated aRCC patients regardless of sarcomatoid status. In a phase II SWOG 1500 study by Pal and colleagues that put cabozantinib, crizotinib, or dacomitinib to the test, the small molecule inhibitor cabozantinib was found most effective in treating 180 patients with metastatic papillary RCC following progression. The exploratory analysis by Plimack and colleagues provide an update of phase III KEYNOTE-426 study which demonstrates that a significant proportion of patients in the pembrolizumab and axitinib arm were able to complete 2 years of pembrolizumab with ongoing clinical benefit. In previous reports of KEYNOTE-426, investigators showed that pembrolizumab plus axitinib prolonged OS and PFS vs sunitinib in patients with treatment-naive advanced RCC.

Emerging data from these trials will position such IO/IO or IO/TKI combination regimens as the new standards of care for patients with renal cell carcinoma. There were several useful additions to the repertoire of currently approved therapies, which should prompt further conversations. As oncologists gear up to gauge the potency of newly available combination regimens in a real-world perspective, significant challenges remain in regard to management of overlapping toxicities, while maintaining quality of life in patients. Ultimately, the rationale for optimal treatment selection for a given combination regimen depends on multi-factorial elements including safety/efficacy, tolerability, cancer progression, comorbidities, drugs cost etc.

I would like to bring your attention to a stimulating roundtable discussion which I chaired, participated by expert panelists Drs. Brian I Rini and Thomas E. Hutson. Full transcript of the roundtable can be accessed here: https://www.kidney-cancer-journal.com/Roundtable.php. This discussion shed light into the robust safety/tolerability portfolio of VEGF-TKIs especially tivozanib which could potentially carve out a space within the area of unmet need : third- or fourth-line therapy for heavily pretreated RCC population. The discussion also integrated new concepts emerging from the phase-3 TIVO-3 trial and analyze the potential impact of novel data. On the heels of the recent US FDA approval of tivozanib (Fotivda) in the relapsed/ refractory RCC setting based on data from phase 3 TIVO-3 trial, tivozanib is now being investigated in combination with the PD-1 inhibitor nivolumab (Opdivo) in the phase 3 TiNivo-2 trial in patients with relapsed/refractory RCC.

The post Editor’s Memo first appeared on GUcancers.

By Christopher Brown

Substances linked to bladder cancer found in the urine of e-cigarette users

Recently published scientific studies found six substances that have a strong link to bladder cancer in the urine of people who had used electronic cigarettes and sometimes other tobacco products. Researchers from the University of North Carolina Lineberger Comprehensive Cancer Center and NYU Langone Health reported in the journal European Urology Oncology.

In this recent study, researchers compiled the results of 22 different studies that analyzed the urine of people who used e-cigarettes or other tobacco products, including cigarettes, to check for evidence of cancer-linked compounds or biomarkers of those compounds. They found six biomarkers or compounds with a strong link to bladder cancer.

Smoking is the No.1 modifiable behavioral risk factor for bladder cancer. There is now evolving literature showing that people who vape may have similar carcinogens in their urine as combustible cigarette users.”

Marc Bjurlin, DO, MSc, associate professor of urology in the UNC School of Medicine

While public health agencies including the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention have warned that there are health risks of vaping, including for e-cigarette-associated lung injury, their safety profile has not been “definitively characterized,” according to Bjurlin and his colleagues.

“The first and foremost side effects that we’re seeing from electronic cigarette use are lung and pulmonary related,” Bjurlin said. “We won’t see the side effects for these other kinds of carcinogenic pathways until much later down the exposure pipeline.”

To develop a better understanding of the long-term risks of vaping, including cancer, researchers investigated possible exposure to substances that can cause bladder cancer in particular since carcinogens could be processed in the body and then passed in urine.

In their review, Bjurlin and his colleagues found 40 different parent compounds that can be processed in the body to produce 63 different toxic chemicals or carcinogenic metabolites, which are substances that remain after in the body after processing.

Six of those chemicals have a strong link to bladder cancer, according to researchers’ analysis of carcinogens databases of the International Agency for Research on Cancer and the Collaborative on Health and the Environment Toxicant and Disease Database.

They found evidence in some studies that e-cigarette users had “significantly” higher levels of several carcinogens that can be metabolized into substances linked to bladder cancer in their urine compared to people who had never used them.

“This finding shows us that people who vape will be exposed to a variety of different carcinogens,” Bjurlin said. “People who have decades of exposure to these carcinogens from vaping may be at risk for developing malignancies, especially bladder cancer.”

There were several limitations to the study, including that researchers did not know the levels of all of the cancer-causing substances in the urine of users from the studies.

In addition, some studies included people who were “dual users,” or people who both smoked and vaped e-cigarettes. There were also cases when users smoked cigarettes and switched to e-cigarettes.

“The study population was quite heterogeneous, meaning that often studies looked at dual users, meaning those who used e-cigarettes and combustible cigarettes,” Bjurlin said. “That made it difficult to assess whether the carcinogen found in the urine was actually from the e-cigarette use or from the cigarette use.”

Further research is needed, said Bjurlin, who wants to determine the threshold of exposure to carcinogens that would lead to development of bladder cancer or other cancer types. He plans to lead a study that will evaluate carcinogens in the urine of e-cigarette users, smokers and non-users.

“Although there is no definitive case yet linking bladder cancer to vaping, it may be reasonable to suspect that decades down the road after exposure to these byproducts, people who vape may be at risk of developing bladder cancer,” he said.

Source: UNC Lineberger Comprehensive Cancer Center

Journal reference:

Bjurlin, M.A., et al. (2020) Carcinogen Biomarkers in the Urine of Electronic Cigarette Users and Implications for the Development of Bladder Cancer: A Systematic Review. European Urology Oncology. doi.org/10.1016/j.euo.2020.02.004.

The post Study Discovers Link Between Electronic Cigarette Use and Bladder Cancer first appeared on GUcancers.

• Christoph Baker

Mar 29 | 2021

National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines to include FOTIVDA^® (tivozanib) as a recommended regimen for third- or fourth- line therapy in patients with clear cell renal cell carcinoma.

National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines to include FOTIVDA^® (tivozanib) as a recommended regimen for third- or fourth- line therapy. The subsequent therapy category follows the first-line treatment regimen recommendations for patients with clear cell histology renal cell carcinoma (ccRCC)), according to AVEO Oncology, the developer of the oral, next-generation VEGF tyrosine kinase inhibitor – FOTIVDA.¹

US FDA approval of tivozanib on March 10, 2021² in the relapsed/ refractory RCC setting based on data from phase 3 TIVO-3 trial, the FDA approved tivozanib for the treatment of adult patients with relapsed or refractory advanced RCC who have received 2 or more prior systemic therapies, based on data from the phase 3 TIVO-3 trial.

On the heels of the recent TIVO-3 results presented during the 2020 ASCO Virtual Scientific Program³ which demonstrated treatment with tivozanib led to a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), US FDA approval of tivozanib on March 10, 2021² in the relapsed/ refractory RCC setting

The findings showed that the final hazard ratio (HR) for OS was 0.97 (P = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib and 19.2 months for sorafenib. A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.

Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; P = .016).

“Fotivda’s addition to the NCCN Guidelines provides further validation for its potential to serve as an important evidence-based, well tolerated treatment option for patients with relapsed or refractory advanced RCC. As previously announced, launch efforts are now underway, and we are committed to bringing this promising therapy to as many appropriate patients as possible.” Michael Bailey, president and chief executive officer of AVEO, stated in a press release.

In the multicenter, open-label, randomized TIVO-3 trial, 350 patients were split evenly between the 2 drugs and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk category and type of previous therapy.³ These patients had to progress on 2 or 3 prior systemic regimens, at least 1 of which had to be a VEGFR tyrosine kinase inhibitor other than sorafenib or tivozanib.

Patients either received 1.5 mg of tivozanib mg orally once a day on 4-week cycles or sorafenib at 400 mg orally twice a day continuously. The primary end point was PFS by independent review in the intention-to-treat population.

The most common grade 3/4 treatment-related adverse events (TRAEs) in the originally published data were hypertension in 20% of patients receiving tivozanib and 14% of patients receiving sorafenib. Serious TRAEs were observed in 11% versus 10% of patients respectively, but no treatment-related deaths were reported.

Tivozanib is now being investigated in combination with the PD-1 inhibitor nivolumab (Opdivo) in the phase 3 TiNivo-2 trial in patients with relapsed/refractory RCC .⁴

BACKGROUND INFORMATION:

The NCCN Clinical Practice Guidelines are the recognized standard for clinical policy in cancer care and are developed through review of evidence and recommendations from physicians and oncology researchers. The current NCCN RCC guidelines categorically make treatment recommendations for first-line or subsequent therapy options for RCC patients. FOTIVDA is now recommended by the NCCN Guidelines as a subsequent therapy for patients with ccRCC who have received two or more prior systemic therapies (Category 2a). FOTIVDA’s addition to the NCCN Guidelines follows its recent U.S. FDA approval, which was based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing FOTIVDA to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The approval was also supported by three additional trials in RCC and included safety data from over 1,000 clinical trial subjects.

About FOTIVDA^® (tivozanib)

FOTIVDA^® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

References

1. AVEO Oncology Announces Addition of FOTIVDA® (tivozanib) into National Comprehensive Cancer Network Clinical Practice Guidelines. Published online March 29, 2021. Accessed March 29, 2021. https://bwnews.pr/3w9zecY.

2. AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. Published online March 10, 2021. Accessed March 10, 2021. https://bwnews.pr/3vbdRY4.

3. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062.

4. AVEO Oncology Announces Collaboration with Bristol Myers Squibb to Evaluate FOTIVDA® (tivozanib) in Combination with OPDIVO® (nivolumab) in Pivotal Phase 3 TiNivo-2 Trial in IO Relapsed Renal Cell Carcinoma. Posted online March 12, 2021. Accessed March 12, 2021. https://bit.ly/3ldIasp

The post Updated NCCN Guideline Recommends Tivozanib Regimen in Clear Cell Renal Cell Carcinoma first appeared on GUcancers.

A list of global guidelines for kidney cancer are provided in this section. These guidelines provide evidence-based recommendations to serve as a guide and support best quality standards of care.

The post Guidelines for Kidney Cancer Treatment first appeared on GUcancers.