PCN92 Temporal Trends in Grade 3/4 Adverse Events and Associated Costs of Nivolumab Plus Cabozantinib (N+C) Versus Sunitinib (S) for Previously Untreated Advanced Renal Cell Carcinoma (aRCC)

Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab (NIVO + IPI) versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (NIVO + IPI, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received NIVO + IPI had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with NIVO + IPI was associated with lower grade 3/4 AE costs than sunitinib.

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1839 EVALUATING THE ASSOCIATION AMONG THE PHARMACOKINETICS OF SUNITINIB, ITS ADVERSE EVENTS AND THE TREATMENT OUTCOMES IN ADVANCED RENAL CELL CARCINOMA

The Journal of Urology ◽

10.1016/j.juro.2013.02.2222 ◽

2013 ◽

Vol 189 (4S) ◽

Author(s):

Norihiko Tsuchiya ◽

Nobuhiro Fujiyama ◽

Shintaro Narita ◽

Takamitsu Inoue ◽

Kazuyuki Numakura ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Treatment Outcomes ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma

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Phase I Trial of 40-kd Branched Pegylated Interferon Alfa-2a for Patients With Advanced Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.5.1312 ◽

2001 ◽

Vol 19 (5) ◽

pp. 1312-1319 ◽

Cited By ~ 70

Author(s):

Robert J. Motzer ◽

Ashok Rakhit ◽

Michelle Ginsberg ◽

Karen Rittweger ◽

Jacqueline Vuky ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Serum Concentration ◽

Phase I ◽

Cell Carcinoma ◽

Renal Cell ◽

Subcutaneous Administration ◽

Interferon Alfa ◽

Advanced Renal Cell Carcinoma ◽

Grade 3 ◽

Dose Limiting Toxicity

PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNα2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNα2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled onto cohorts of three or six patients. PEG-IFN was administered on a weekly basis by subcutaneous injection. The dose was escalated from 180 μg/wk to a maximum of 540 μg/wk in 90-μg increments. Serial venous blood samples were drawn to assess concentrations of PEG-IFN and two immunologic surrogates, neopterin and 2′-5′ oligoadenylate synthetase (OAS). RESULTS: The maximum-tolerated dose was determined as 540 μg/wk, because two patients experienced dose-limiting toxicity within 28 days of starting treatment. One developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue. Six patients were treated at 450 μg/wk without dose-limiting toxicity. Over the course of treatment, the side-effect profile was mostly mild to moderate in intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and decreased appetite. Five patients (19%) achieved a partial response. The mean maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180 μg/wk to 540 μg/wk. Serum concentration of PEG-IFN was sustained at close to peak during the dosing interval, and steady-state was achieved in approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were induced at all doses with a sustained concentration profile similar to PEG-IFN. CONCLUSION: PEG-IFN is a modified form of IFNα2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 μg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNα and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNα.

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Difference in adverse-event profiles between mTOR inhibitors, temsirolimus, and everolimus for advanced renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.461 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 461-461 ◽

Cited By ~ 1

Author(s):

Masahiro Nozawa ◽

Takashi Kikuchi ◽

Mitsutoshi Nishimoto ◽

Yasuyuki Kobayashi ◽

Hirotsugu Uemura

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Event ◽

Adverse Events ◽

Cell Carcinoma ◽

Renal Cell ◽

Mtor Inhibitors ◽

Two Agents ◽

Significant Difference ◽

The Difference ◽

Grade 3

461 Background: Everolimus and temsirolimus have proven their efficacy and are used for patients with metastatic renal cell carcinoma (mRCC). They both are rapamycin derivatives and are categorized as mTOR inhibitors. There have been few reports that examined the difference between these two agents regarding adverse events. Our objective was to investigate the difference in the safety of both agents on the basis of our clinical experience. Methods: We identified patients with mRCC who had been treated with everolimus or temsirolimus at our hospital. Treatment duration, relative dose intensity, laboratory data, and adverse events during treatment with each agent were evaluated. Results: A total of 55 patients were evaluable. 43 of those had been treated with everolimus, 22 with temsirolimus, and 10 with both agents. There was no significant difference in age and gender between the two treatment groups. Median treatment durations of the everolimus and temsirolimus groups were 2.4 months and 1.8 months, respectively. Relative dose intensities of the everolimus and temsirolimus groups were 71.6 % and 75.4 %, respectively. Anemia, hyperglycemia, stomatitis, and interstitial lung disease (ILD) were detected with higher frequency in the everolimus group. In the everolimus group, 31 % of patients developed any grade of ILD including 15 % of grade 3, whereas ILD was reported in only one patient treated with temsirolimus with no grade 3 or higher. Frequencies of adverse events of grade 3 or higher were 49 % in the everolimus group and 26 % in the temsirolimus group. Conclusions: Adverse-event profiles of everolimus and temsirolimus may differ from each other. Respiratory disorders may occur more frequently and severely in patients treated with everolimus than temsirolimus. These findings suggest the difference in the pharmacodynamics, pharmacokinetics, and treatment regimen of these two agents may result in different adverse events even though they target the same molecule.

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Combination of immunotherapy and tyrosine kinase inhibitor in first-line metastatic renal cell carcinoma: A real-world Indian experience.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16576 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16576-e16576

Author(s):

Amit Rauthan ◽

Poonam Patil ◽

Nitin Yashas Murthy ◽

SP Somashekhar ◽

Shabber Zaveri ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Adverse Events ◽

Tyrosine Kinase ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Grade 3

e16576 Background: Immuno-oncology (IO) agents in combination with oral tyrosine kinase inhibitors (TKIs) has become a standard first line therapy in metastatic renal cell carcinoma (mRCC) patients. Various combinations such as pembrolizumab + axitinib, avelumab + axitinib, nivolumab + cabozantinib and pembrolizumab + lenvatinib have all shown better results than sunitinib. There is very limited data about this from India. Methods: This is a single center, retrospective study of mRCC patients, who received first line treatment was nivolumab or pembrolizumab with axitinib or lenvatinib. The endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AE). Results: Between Jan 2019 to Jan 2021, 22 patients were treated with IO + TKI combination. 12 patients received axitinib, and 10 lenvatinib. Age range was 35 to 78 years with 18 males and 4 females. IMDC risk stratification showed 3 favorable (13.6%), 13 intermediate (59%) and 6 poor risk (27.2%) patients. 2 patients (9%) achieved complete response(CR), 13 (59%) partial response (PR), 4 (18.2%) had stable disease and 3 (13.6%) progressed. The ORR was 68%. Median PFS was 22 months (1 month- 24 months). OS at 1 year was 92%, and median OS was not reached. Grade 3/4 immune related adverse events (AEs) were seen in 3 (14.2%) patients (1 colitis,1 pneumonitis,1 encephalitis), for whom the IO was discontinued. TKI related grade 3/4 AEs were seen in 8 patients (38%), and were managed with dose reductions. Conclusions: Combination IO + TKI is a very effective first line therapy in mRCC. An ORR of 68%, median PFS of 22 months and 1 year OS of 92% is the best we have seen in our patients. The efficacy of this combination is seen in all IMDC subgroups. The combination is well tolerated, and the TKI AEs are comfortably managed with dose reduction. IO combinations should be preferred over single agent TKIs (sunitinib or pazopanib) as first line therapy.

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Nivolumab and Ipilimumab Immunotherapy for Hemodialysis Patients with Advanced Renal Cell Carcinoma

Current Oncology ◽

10.3747/co.27.6439 ◽

2020 ◽

Vol 27 (4) ◽

pp. 225-228

Author(s):

Y. Kobayashi ◽

H. Arai ◽

M. Honda

Keyword(s):

Renal Cell Carcinoma ◽

Renal Function ◽

Adverse Events ◽

Cell Carcinoma ◽

Immune Checkpoint ◽

Renal Cell ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Advanced Renal Cell Carcinoma ◽

Safety And Efficacy

Combined immune checkpoint blockade with nivolumab and ipilimumab is standard therapy for the treatment of patients with previously untreated advanced renal cell carcinoma who are at intermediate or poor risk. However, data about the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in patients on hemodialysis are limited. Renal function has no known clinically important effects on the pharmacokinetics and clearance of nivolumab and ipilimumab. Further, most immune-related adverse events in patients on hemodialysis are thought to be manageable with the same treatments applied in patients with normal renal function. We present a case of advanced clear-cell renal cell carcinoma in a patient on hemodialysis who received combined immune checkpoint blockade with nivolumab and ipilimumab and who showed no evident signs of immune-related adverse events. Here, we confirm the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in a patient on hemodialysis.

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