Chair, Sumanta Kumar Pal, MD, FASCO, David F. McDermott, MD, and Tian Zhang, MD, MHS, prepared useful Practice Aids pertaining to renal cell carcinoma for this CME/MOC activity titled “Breaking New Ground in RCC Management: Expert Guidance on Leveraging Therapeutic Strategies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/3AB7i5r. CME/MOC credit will be available until March 16, 2024.

1. Patient Education:
Understanding Renal Cell Carcinoma Treatment Options
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
Receiving a diagnosis of renal cell carcinoma (RCC) can be
overwhelming for patients and their caregivers. Please use the
following one-page, printable resource to help your patients and
their caregivers understand RCC treatment options and where
they can turn for more support.
Printable Resource

2. Understanding Kidney Cancer: A Quick Reference for Patients
If you or someone you love has been diagnosed with kidney cancer—also called renal cell carcinoma
or RCC—you may have a lot of questions about treatment options and where you can turn for help.
What You Need to Know About Kidney Cancer Treatment
What are the different kinds of kidney cancer?
There are a variety of kidney cancers; some include clear cell, papillary, and chromophobe.
What do staging and grading refer to, and what do they mean for treatment?
• Kidney cancer is staged—or classified—by the size of the tumor and whether it has
spread beyond the original tumor; stage 1 tumors are small and localized, while stage 4
tumors have spread to nearby and possibly distant organs and lymph nodes.
• Cancer grading refers to how aggressive the cells look under a microscope and also
uses a 1 to 4 scale, with 1 being the least and 4 the most aggressive.
Staging and grading provide the treatment team with information on how
quickly a cancer is expected to grow and how likely it is to recur. The patient and
cancer care team will consider these factors when choosing a treatment plan.
What treatments are available?
Patients with small tumors that have not spread to other parts of the body may be treated
with surgery or, in some cases, radiation. Patients with more advanced kidney cancer
that has spread beyond the kidney may require immunotherapy, which is a treatment
that uses a person’s own immune system to fight cancer; targeted therapies, which
target specific changes in a cancer cell to block its growth and spread; or combinations
of immunotherapy and/or targeted agents.
Your team will let you know what to expect from each treatment, including
how the medicine is given, which side effects are common, and how the medication
may affect your lifestyle, so you and your team can choose a treatment
plan that best fits your needs.
What side effects are associated with kidney cancer treatments?
Side effects vary by treatment, and not all patients have the same experience with each
agent. Patients receiving immunotherapy or targeted therapies may experience diarrhea,
rashes, fatigue, and other issues, depending on the particular treatment.
If you think you may be experiencing a side effect, it is important to let your cancer
care team know right away. Your provider may adjust or change your treatment, as
the goal is for you to receive treatment as long as possible to achieve optimal
results while maintaining your quality of life.
Spotlight on Clinical Trials
Your cancer care team may offer you the option of enrolling
in a clinical trial. These studies provide important information
on whether a treatment is safe and effective and give you
access to new strategies that could be better than the
options currently used.
Clinical trial enrollment is voluntary. Each trial has
specific enrollment criteria (eg, age, type of cancer,
stage, prior treatments). Talk to your cancer care team
about whether clinical trial enrollment
is right for you.
Where Can You Get More Support?
Online and in-person advocacy foundations for patients and
their caregivers provide a variety of services, including
support groups, counseling, financial assistance, information
on treatments and clinical trials, opportunities to support and
participate in research, and educational workshops.
 KCCure: kccure.org
 Kidney Cancer Association: kidneycancer.org
 Action to Cure Kidney Cancer: ackc.org
 KidneyCAN: kidneycan.org
 International Kidney Cancer Coalition: ikcc.org
 CancerCare: cancercare.org/support_groups/137-
kidney_cancer_patient_support_group
 American Cancer Society: cancer.org
Visit the links below to learn more about the resources
each organization offers.

3. Current Approvals and Future Directions in RCC Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
IO + VEGFR TKI Combination Regimens
IO + IO Combination Regimens
Frontline
Advanced
Disease
Selected Phase 3 Trials in
the First-Line Setting9
PDIGREE (NCT03793166)
Nivolumab + ipilimumab → nivolumab vs
nivolumab + ipilimumab → nivolumab +
cabozantinib
COSMIC-313 (NCT03937219)
Cabozantinib + nivolumab + ipilimumab vs
placebo + nivolumab + ipilimumab
LITESPARK-012 (NCT04736706)
Pembrolizumab + belzutifan + lenvatinib or
pembrolizumab/quavonlimab + lenvatinib
vs pembrolizumab + lenvatinib
NCT03873402
Nivolumab + ipilimumab vs nivolumab
Pembrolizumab 200 mg every 3 wk or
400 mg every 6 wk in combination with
axitinib 5 mg PO twice daily
Nivolumab 3 mg/kg followed by ipilimumab
1 mg/kg on the same day every 3 wk for
4 doses, then nivolumab 240 mg every 2 wk
or 480 mg every 4 wk as a single agent
Nivolumab 240 mg every 2 wk or
480 mg every 4 wk in combination with
cabozantinib 40 mg PO once daily without food
Avelumab 800 mg every 2 wk in combination
with axitinib 5 mg PO twice daily
Pembrolizumab 200 mg every 3 wk or
400 mg every 6 wk in combination with
lenvatinib 20 mg PO once daily
Pembrolizumab + Axitinib4,5
Approved April 2019 based on the
phase 3 KEYNOTE-426 trial
NCCN3
category 1 for all risk groups (preferred)
Nivolumab + Ipilimumab1,2
Approved April 2018 for intermediate-risk or poor-risk
disease based on the phase 3 CheckMate -214 trial
NCCN3
category 1 for intermediate or poor
risk (preferred); category 2A for favorable risk
(other recommended regimen)
Nivolumab + Cabozantinib1,7
Approved January 2021 based on the
phase 3 CheckMate -9ER trial
NCCN3
category 1 for all risk groups (preferred)
Avelumab + Axitinib5,6
Approved May 2019 based on the
phase 3 JAVELIN Renal 101 trial
NCCN3
category 2A for all risk groups
(other recommended regimen)
Pembrolizumab + Lenvatinib4,8
Approved August 2021 based on the phase 3 CLEAR trial
NCCN3
category 1 for all risk groups (preferred)

4. Current Approvals and Future Directions in RCC Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
IO Monotherapy Regimen
Select VEGFR TKI Regimens
Pretreated
Advanced
Disease
Nivolumab 240 mg every 2 wk or
480 mg every 4 wk
Selected Trials in
the Later-Line Setting9
Phase 3 CONTACT-03 (NCT04338269)
Atezolizumab + cabozantinib vs
cabozantinib
Phase 3 TiNivo-2 (NCT04987203)
Tivozanib + nivolumab vs tivozanib
Phase 3 LITESPARK-005 (NCT04195750)
Belzutifan vs everolimus
Phase 2 FRACTION-RCC (NCT02996110)
Nivolumab + ipilimumab
vs nivolumab + relatlimab
Phase 2 LITESPARK-003 (NCT03634540)
Belzutifan + cabozantinib
Phase 3 LITESPARK-011 (NCT04586231)
Belzutifan + lenvatinib vs cabozantinib
Cabozantinib 60 mg PO once daily
without food
Tivozanib 1.34 mg PO once daily with or
without food for 21 d on treatment followed
by 7 d off treatment (28-d cycle)
Lenvatinib 18 mg PO once daily with
everolimus 5 mg PO once daily; modify the
recommended daily dose for certain patients
with renal or hepatic impairment
Nivolumab1
Approved November 2015 in patients who have received
prior antiangiogenic therapy based on the
phase 3 CheckMate -025 trial
NCCN3
category 2A (IO therapy naïve)
Cabozantinib7
Approved April 2016 based on the phase 3 METEOR trial
NCCN3
category 2A (after prior IO therapy or IO therapy naïve)
Tivozanib11
Approved March 2021 in patients with relapsed or
refractory advanced RCC following ≥2 prior systemic
therapies based on the phase 3 TIVO-3 trial
NCCN3
category 2A (after prior IO therapy)
Lenvatinib + Everolimus8,10
Approved May 2016 in patients with advanced RCC following
1 prior antiangiogenic therapy based on the phase 2
HOPE 205 trial
NCCN3
category 2A (after prior IO therapy or IO therapy naïve)

5. Current Approvals and Future Directions in RCC Therapy
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
1. Opdivo (nivolumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125554s108lbl.pdf. 2. Yervoy (ipilimumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125377s124lbl.pdf. 3. NCCN Clinical
Practice Guidelines in Oncology. Kidney Cancer. Version 4.2023. https://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf. 4. Keytruda (pembrolizumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s128lbl.pdf. 5. Inlyta
(axitinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/202324Orig1s014CorrectedLbl.pdf. 6. Bavencio (avelumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761049s013lbl.pdf. 7. Cabometyx
(cabozantinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208692s014lbl.pdf. 8. Lenvima (lenvatinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206947s024lbl.pdf. 9. https://clinicaltrials.gov.
10. Afinitor (everolimus) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/203985s023,022334s051lbl.pdf. 11. Fotivda (tivozanib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212904s000lbl.pdf. 12. Sutent
(sunitinib malate) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021938s039lbledt.pdf.
Selected Phase 3 Trials in
the Adjuvant Setting9
CheckMate -914 (NCT03138512)
Nivolumab + ipilimumab vs placebo (Part A)
Nivolumab vs placebo (Part B)
RAMPART (NCT03288532)
Durvalumab ± tremelimumab vs
active surveillance
LITESPARK-022 (NCT05239728)
Belzutifan + pembrolizumab vs
placebo + pembrolizumab
VEGFR TKI Regimen
IO Regimen
Adjuvant
Setting
Sunitinib 50 mg PO once daily with or
without food, 4 wk on treatment followed by
2 wk off treatment for nine 6-wk cycles
200 mg every 3 wk or
400 mg every 6 wk
Sunitinib12
Approved November 2017 in adult patients at
high risk of recurrence following nephrectomy
based on the phase 3 S-TRAC trial
NCCN3
category 3
Pembrolizumab4
Approved November 2021 for the adjuvant treatment
of patients with RCC at intermediate/high or high risk
of recurrence following nephrectomy or following
nephrectomy and resection of
metastatic lesions based on the KEYNOTE-564 trial
NCCN3
category 2A

6. Potential Adverse Events Associated With Immune Checkpoint Inhibitor and TKI
Combination Regimens: Patient Perspectives and Guides for Management1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
Combination Treatments and Dose Reduction: Understanding the Patient’s Viewpoint
Results From a Recent Patient Survey Focusing
on the Use of Combination Treatment Regimensa
Was the dose
reduction helpful?
It helped a lot
76%
It did not make
a difference 6%
It helped
a little
18%
Have you ever not taken your oral
therapy to reduce side effects
(without telling your doctor)?
No
82%
Yes
18%
No
60%
Yes
40%
Patient Views Related to Oral Dose Reduction (While on Combination Therapy)
No
84%
Yes
16%
No
58%
Yes
42%
Asked for a dose reduction Felt relieved Worried about reducing efficacy
By encouraging patients to report any AEs right away, providers may be able to suggest
AE management strategies, including dose adjustments, that allow patients to keep
receiving an effective treatment as long as possible while maintaining quality of life.
KCCure’s Research Helps Inform
Providers of the Patient Voice
The Kidney Cancer Research Alliance
(KCCure) provides answers to
questions that patients and
caregivers are asking.
Wherever they are in their diagnosis,
patients can visit
kccure.org
to find updated information on the
different types of kidney cancer, new
treatment options, and more.
KCCure also conducts its own
patient-centered research aimed
at improving the quality of life of all
patients with kidney cancer by better
identifying and defining patients’
needs and concerns.
Yes
66%
No
34%
Due to side effects, did your doctor
reduce the dose of your oral therapy
(while on combination tx)?

7. Potential Adverse Events Associated With Immune Checkpoint Inhibitor and TKI
Combination Regimens: Patient Perspectives and Guides for Management1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
• irAEs are often diagnosed by
exclusion; other causes should be
ruled out (including AEs associated
with other therapies used), but
immunotherapy-related toxicity
should always be included in the
differential
• There should be a high level of
suspicion that new symptoms are
treatment related; early
recognition, evaluation, and
treatment of irAEs, and patient
education are essential for the
best outcomes
• Depending on severity of the irAEs,
management may require a
corticosteroid as well as
interruption or discontinuation
of therapy
• If appropriate, use immuno-
suppressive treatment; patients
generally recover from irAEs
How should irAEs be
diagnosed and managed?
What are the general
recommendations
for management?2-5
Musculoskeletal
Gastrointestinal
Renal
Hematologic
Neurologic
Pulmonary
Cardiovascular
Ocular
Dermatologic
Endocrine
Spectrum of irAEs1
Neuropathy, meningitis,
Guillain–Barré syndrome,
myasthenia gravis, encephalitis,
and transverse myelitis
Myocarditis, pericarditis,
arrhythmias, impaired ventricular
function with heart failure and
vasculitis, and venous
thromboembolism
Pneumonitis
Colitis, hepatitis, and elevated
hepatic transaminases
Inflammatory arthritis, myositis,
and polymyalgia-like syndrome
Uveitis/iritis, episcleritis, and blepharitis
Primary hypothyroidism,
hyperthyroidism, hypophysitis,
primary adrenal insufficiency,
and diabetes
Rash/inflammatory dermatitis,
bullous dermatoses, and severe
cutaneous adverse reactions
Autoimmune hemolytic anemia,
aTTP, hemolytic uremic syndrome,
aplastic anemia, lymphopenia, ITP,
and acquired hemophilia
Nephritis
Why do irAEs occur?
“Taking the brakes off” of the immune system can
help the body fight cancer, but it can also lead to
toxicity from a “supercharged” immune system.
Immune checkpoint inhibitors are associated with
important clinical benefits, but general immunologic
enhancement can also lead to a unique spectrum
of immune-related adverse events (irAEs).1

8. Potential Adverse Events Associated With Immune Checkpoint Inhibitor and TKI
Combination Regimens: Patient Perspectives and Guides for Management1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
irAE Management Guidelines
Available from
ASCO,2
NCCN,3
SITC,4
and ESMO5
Grade 1
Minimal or no symptoms; diagnostic changes only
• In general, checkpoint inhibitor therapy should be continued with close monitoring,
with the exception of some neurologic, hematologic, and cardiac toxicities
Grade 2
Mild to moderate symptoms
• Hold checkpoint inhibitor therapy for most grade 2 toxicities
• Consider resuming immunotherapy when symptoms and/or laboratory values revert
to grade 1 or lower
Grade 3
Severe or life-threatening symptoms
• Hold checkpoint inhibitor therapy
• Initiate high-dose corticosteroids (prednisone 1-2 mg/kg/d or methylprednisolone IV
1-2 mg/kg/d)
• If symptoms do not improve within 48-72 hours of initiating high-dose corticosteroids,
infliximab may be offered for some toxicities
• Taper corticosteroids over the course of at least 4-6 weeks
• When symptoms and/or laboratory values revert to grade 1 or lower, rechallenging
with immunotherapy may be offered; however, caution is advised, especially in those
patients with early-onset irAEs; dose adjustments are not recommended
Grade 4
Severe or life-threatening symptoms
• In general, permanent discontinuation of checkpoint inhibitor therapy is warranted, with
the exception of endocrinopathies that have been controlled by hormone replacement
Be aware of overlapping toxicities that can occur
with IO + TKI combination therapy
IO
Pruritus
Pneumonitis
Myocarditis
Adrenal crisis
TKI
Hypertension
Taste changes
Stomatitis
Dyspepsia
Cytopenias
HFSR
PRES
Encephalitis
Rash
Diarrhea
Hepatitis
Hypothyroid
AMS
IO + TKI Combination Toxicities6
• It is important to determine the causative therapy to
plan a management strategy
– Hold TKI (shorter half-life than checkpoint inhibitor)
– If symptoms resolve in a few days, TKI was likely
the cause

9. Potential Adverse Events Associated With Immune Checkpoint Inhibitor and TKI
Combination Regimens: Patient Perspectives and Guides for Management1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
For frequent, watery, bloody, or nocturnal stools, or any diarrhea or
abdominal distress, patients should notify medical team immediately
Diarrhea8
Common adverse events associated with TKIs include fatigue, diarrhea, and hand-foot skin reaction7,8
Fatigue8
Educating your patients on managing fatigue is essential
• Staying as active as possible helps regulate sleep
• Maintain a normal work and social schedule
• Take breaks as needed
• Tell your medical team if activity is intolerable or fatigue worsens
Patient Education
• Loperamide is usually effective
• If loperamide is ineffective, consider diphenoxylate/atropine
Medical Intervention
• Monitor bowel habits, and report any increase in activity above normal
• Avoid spicy or fatty foods; plain, simple foods are best
• Avoid fruit and caffeine
• Maintain adequate fluid intake to avoid dehydration
• Monitor/manage electrolytes
General Management

10. Potential Adverse Events Associated With Immune Checkpoint Inhibitor and TKI
Combination Regimens: Patient Perspectives and Guides for Management1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/FFQ40
a
Patient survey data; June to September 2022; US and global participation; N = 119.
1. Postow MA et al. NEnglJMed. 2018;378:158-168. 2. Brahmer JR et al. JClinOncol. 2018;36:1714-1768. 3. NCCN Clinical Practice Guidelines in Oncology. Management of Immunotherapy-Related Toxicities. Version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.
4. Rini BI et al. J Immunother Cancer. 2019;7:354. 5. Haanen JBAG et al. Ann Oncol. 2017;28(suppl_4):iv119-iv142. 6. https://www.urotoday.com/conference-highlights/asco-gu-2020/asco-gu-2020-kidney-cancer/119282-asco-gu-2020-toxicity-profiles-and-sideeffectmanagement-of-
first-line-treatment-options-of-renal-cell-carcinoma.html. 7. Walko CM et al. Semin Oncol. 2014;41(suppl 2):s17-s28. 8. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. 9. McLellan B et al. Ann Oncol. 2015;26:2017-2026. 10. Lacouture ME et al.
Oncologist. 2008;13:1001-1011. 11. Brose MS et al. Semin Oncol. 2014;41(suppl 2):s1-s16.
1
Tingling and/or numbness, accompanied by minimal skin
changes or dermatitis, such as erythema, edema, or
hyperkeratosis of the hands and/or feet without pain;
does not disrupt ADLs
2
Skin changes of the hands and/or feet; may include peeling,
blisters, bleeding, edema, or hyperkeratosis with pain;
discomfort affecting ADLs
3
Severe skin changes of the hands and/or feet; may include
peeling, blisters, bleeding, edema, or hyperkeratosis
with pain and/or severe discomfort causing inability to work
or perform ADLs
Grade8
Characteristic9
Hand-Foot Skin Reactions
Avoid hot water, wear thick socks, wear cotton
gloves/socks at night, use moisturizing creams and
keratolytics (urea 20% to 40%; salicylic acid
5% to 10%); no dose reduction needed;
follow up within 2 wk
Employ grade 1 strategies, consider clobetasol
0.05% ointment 2x/d for erythematous areas, use topical
and systemic analgesics (if no contraindications
[eg, bleeding, kidney dysfunction]);
consider 50% dose reduction for 7-28 d
until HFSR is grade 1/0 → full dose
Employ grade 1/2 strategies; treatment interruption for
≥7 d until HFSR is grade 1/0 → 50% of full dose
→ escalation, if possible; resume treatment
at lower dose as recommended in package insert;
dose may be escalated
if reaction does not reoccur
Management7,9-11