37
2020 Spring Oncology Conference
2020 Spring Oncology Conference
Raising the Bar for the Standard of Care: Advances in the Management of Advanced
Renal Cell Carcinoma
3
• Formulate treatment strategies for advanced renal cell carcinoma (RCC) based on
current evidence and patient/disease factors
• Identify potential immune-related adverse events (AEs) and their onset during and
after therapy
• Implement strategies to recognize and appropriately manage side effects
associated with tyrosine kinase inhibitors (TKIs) for advanced RCC
Learning Objectives
4
• More than 50% of patients with RCC have no symptoms
‒ Diagnosis is through incidental imaging of the abdomen or chest ordered for unrelated
symptoms
• Hematuria serves as a warning sign: necessitates further evaluation and imaging leading
to a diagnosis and treatment plan
• Solid tumors are managed by size
‒ 20% of tumors >3 cm discovered incidentally will be benign
‒ Tumors ≥4 cm have metastatic potential
• Treatment options include active surveillance, ablation, nephron-sparing tumor excision,
nephrectomy, and systemic treatment
• Predictors of a poor prognosis include poor functional status and metastasis
Overview of RCC
Gray RE, Harris GT. Am Fam Physician. 2019;99:179-184.
5
RCC Statistics
National Cancer Institute Surveillance, Epidemiology, and End Results Program. seer.cancer.gov/statfacts/html/kidrp.html; Accessed Mar 26, 2020.
• 8th most common cancer – more common in men than women – representing 4.2% of all new cancers in the US
• In 2019, there were ~73,820 new cases of kidney and renal pelvis cancer and ~14,770 deaths from this disease
65%
17%
16%
3%
Percent of Cases by Stage
Localized (Confinedto Primary Site)
Regional (Spread toRegional LymphNodes)
Distant (Cancer HasMetastasized)
Unknown (Unstaged)
92.5%
69.6%
12.0%
41.9%
0%
20%
40%
60%
80%
100%
Perc
en
t S
urv
ivin
g
Stage
5-Year Relative Survival
Localized Regional Distant Unknown
6
• Hereditary factors include familial syndromes, including:
‒ von Hippel-Lindau syndrome
‒ Hereditary type 1 papillary renal carcinoma
‒ Familial renal oncocytoma
‒ Birt-Hogg-Dube syndrome
• Few risk factors for RCC have been established
‒ Nonhereditary risk factors that possibly contribute to RCC include:
• Cigarette smoking (increases in a dose-dependent fashion)
• Obesity, particularly in women (as weight increases, risk of RCC increases)
• Older age (median age at diagnosis: 64 years)
Risk Factors for RCC
Chow WH, et al. Nat Rev Urol. 2010;7:245-257; Sachdeva K, et al. emedicine.medscape.com/article/281340-overview#showall.
Accessed Mar 26, 2020.
7
• Clear-cell RCC is the most common variety: 70% to 90%
• Non−clear-cell RCC includes:
‒ Papillary: 10% to 15%
‒ Chromophobe: 3% to 5%
‒ Collecting duct: 1% to 2%
‒ Unclassified: 4% to 6%
• In one study of 254 patients with advanced RCC, 16.1% harbored pathogenic germline
mutations
‒ More than 20% of patients with non−clear-cell RCC had germline mutations
• Sarcomatoid or rhabdoid features can be associated with any histology
‒ Harbinger of a poor prognosis in the VEGF TKI era
Histology of RCC
VEGF = vascular endothelial growth factor.
Carlo MI, et al. JAMA Oncol. 2018;4:1228-1235; Muglia VF, Prando A. Radiol Bras. 2015;48:166-174; Warren AY, Harrison D. World J Urol.
2018;36:1913-1926.
8
Patient Factors to Consider When Selecting Therapy
• Comorbidities, especially conditions that affect a patient’s immune status
• Symptoms of disease
• Sites of disease
• ECOG PS
• Histology
• Risk stratification
• Medication history, including use of steroids
ECOG PS = Eastern Cooperative Oncology Group performance status.
Heng DY, et al. J Clin Oncol. 2009;27:5794-5799; Heng DY, et al. Lancet Oncol. 2013;14:141-148; van der Zanden LF, et al. Urol Oncol.
2017;35:e9-e16.
9
IMDC Criteria Risk Factors
Yes (1)/
No (0)
KPS <80% 1/0
Time from diagnosis <12 months 1/0
Hemoglobin <LLN 1/0
Neutrophil count >ULN 1/0
Platelet count >ULN 1/0
Corrected serum calcium >ULN 1/0
Risk Stratification: Laboratory and Clinical
KPS = Karnofsky Performance Status; LLN = lower limit of normal; ULN = upper limit of normal.
IMDC, International Metastatic RCC Database Consortium.
Heng DY, et al. J Clin Oncol. 2009;27:5794-5799; Heng DY, et al. Lancet Oncol. 2013;14:141-148.
Risk Group by Number of Risk Factors
Favorable 0
Intermediate 1-2
Poor 3-6
• Current FDA indications restrict certain treatments based on these risk categories
10
• Goal of therapy is different for each patient
‒ May be curative vs improvement in length and/or quality of life, depending on
staging
• For active sites of disease
‒ Medical treatments aim to shrink and destroy the cancer
‒ Surgical treatment aims to remove the cancer
‒ Ablative treatments (eg, radiation or thermal) aim to destroy local disease
• For patients with multiple sites of disease, the mainstay treatment has been
medical/systemic therapy
Goals of Treatment
Choueiri TK, et al. J Urol. 2011;185:60-66; NCCN Guidelines. Kidney cancer. www.nccn.org/professionals/physician_gls/pdf/kidney.pdf.
Accessed Mar 26, 2020.
11
Changing Treatment Landscape for Metastatic RCC
mRCC = metastatic renal cell carcinoma.
Klaassen Z. www.urotoday.com/conference-highlights/asco-2019-annual-meeting/asco-2019-kidney-cancer/113076-asco-2019-evolving-front-line-
therapy-in-metastatic-renal-cell-carcinoma.html. Accessed Mar 26, 2020.
• In the last 15 years, the landscape of treatment for clear-cell mRCC has changed immensely
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
Sorafenib Temsirolimus Axitinib Nivolumab +
Ipilimumab
Sunitinib Bevacizumab + IFN-⍺Everolimus
Pazopanib
Nivolumab
Cabozantinib
Everolimus + Levatinib
Pembrolizumab
+Axitinib
Avelumab
+ Axitinib
Targeted Therapy Era Immunotherapy Combination Era
12
• T-cell activation is required for
effective antitumor response
• PD-1 and CTLA-4 expressed on
T cells act as “off” switches to down-
regulate the immune response
• Tumor cells can masquerade as
normal cells by expressing PD-L1
• Blockade of PD-1 and PD-L1
and CTLA-4 ultimately allow
up-regulation of immune responses
targeting the tumor
Immunotherapy Mechanism of Action
CTLA-4 = cytotoxic T-lymphocyte antigen 4; PD-1 = programmed cell death protein; PD-L1 = programmed death-ligand 1.
Buchbinder EI, Desai A. Am J Clin Oncol. 2016;39:98-106; Institute for Clinical Immuno-Oncology. www.accc-cancer.org/docs/immuno-
oncology/iclio-webinar-new-mechanisms-of-action-v3-final. Accessed Mar 26, 2020; Tarhini A, et al. Cancer Biother Radiopharm. 2010;25:601-613.
Activated T cell
Tumor cell
death
PD-L1
Anti-PD-1
PD-1
TCR
MHCTCR
MHC
CD28
B7
Anti-
CTLA-4
CTLA-4
Renal cancer
cell
Antigen-presenting
cell
T cell
13
• Boosts the RCC armamentarium
• VEGF inhibitors infiltrate T cells into
tumors and enhance antitumor
immunity
• Adding PD-1 inhibitors may augment
these effects
• Standard of care has shifted to
immunotherapy-based combination
regimens in the 1st-line setting
Targeted Therapy Plus Immunotherapy in Advanced RCC
Garje R, et al. Cancers (Basel). 2020;12:143.
Anticancer Immunity
Anti-VEGFVEGF TKI
Anti-PD-1
Anti-PD-L1
VEGF/R
Myeloid
DCs
PD-1
PD-L1
CD3
CD3
CD4
CD3 APCTreg
MDSCs
Macrophage
(M2 phenotype)Tumor
14
Case Study 1: Oliver
• 63-year-old African American man presented for evaluation of hematuria and
urinary obstruction
• Medical history notable for hypertension and ongoing smoking
• CT scan showed a left renal mass: 13.3 x 12.3 x 10 cm
• Imaging revealed multiple lung nodules measuring up to 1.5 cm, consistent with
metastatic disease
• Oliver underwent biopsy of a lung nodule
‒ Pathology revealed metastatic clear-cell RCC with no sarcomatoid features
• Oliver has a good PS and no additional IMDC risk factors other than needing
systemic therapy within a year of diagnosis
PS = performance status.
15
Risk Status First-line Therapy
Preferred regimens
Favorable risk
Poor/intermediate
risk
• Axitinib + pembrolizumab
• Pazopanib
• Sunitinib
• Axitinib + pembrolizumab
• Ipilimumab + nivolumab
• Cabozantinib
Other recommended regimens
Favorable risk
Poor/intermediate
risk
• Ipilimumab + nivolumab
• Cabozantinib
• Axitinib + avelumab
• Pazopanib
• Sunitinib
• Axitinib + avelumab
Guidelines for Recurrent or Advanced Clear-Cell RCC: First-line Therapy
NCCN Guidelines. Kidney cancer. www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed Mar 26, 2020.
16
0 4 8 12 16 18 24
KEYNOTE-426: Pembrolizumab + Axitinib in Treatment-naïve Advanced RCC
CR = complete response; ITT = intent to treat; ORR = overall response rate;
OS = overall survival; PFS = progression-free survival;
VEGFR = vascular endothelial growth factor receptor.
Rini BI, et al. N Engl J Med. 2019;380:1116-1127.
• Pembrolizumab is an anti–PD-1 antibody that
has shown antitumor activity
• Axitinib is a highly potent VEGFR-TKI
approved in the 2nd-line setting and has
shown antitumor activity in the 1st-line setting
• Combination pembrolizumab + axitinib
demonstrated high PFS, ORR, and OS
vs sunitinib
‒ OS in the ITT population at 12 months:
89.9% vs 78.3%
• Benefit observed in all IMDC subgroups
and PD-L1 expression categories
‒ PFS: 15.1 vs 11.1 months
‒ ORR: 59.3% vs 35.7% (CR: 5.8% vs 1.9%)
OS in ITT Population
Pa
tie
nts
Wh
o W
ere
Aliv
e (
%)
Months
Pembrolizumab + axitinib
Sunitinib
100
90
80
70
60
50
40
30
20
10
0
Hazard ratio for death, 0.53 (95% CI, 0.38-0.74)
P <0.0001
17
• PD-L1 inhibitor avelumab was studied in
combination with axitinib (VEGFR-TKI) vs
sunitinib
• Patients stratified by ECOG PS and
geographic region
• Improvements seen in patients with PD-L1–
positive tumors
‒ Median PFS: 13.8 vs 7.2 months
‒ ORR: 55.2% vs 25.5%
‒ Median OS: 11.6 vs 10.7 months (NS);
longer follow-up needed
• PFS benefit maintained in overall population
as well, regardless of PD-L1 status
JAVELIN Renal 101: Avelumab + Axitinibvs Sunitinib as First-line Treatment
Motzer RJ, et al. N Engl J Med. 2019;380:1103-1115.
PFS in Patients With PD-L1-Positive Tumors
Avelumab + axitinib
Sunitinib
100
90
80
70
60
50
40
30
20
10
0P
FS
(%
)
0 2 4 6 8 10 12 14 16 18 20 22 24
Months
18
• Combination of checkpoint inhibitors
nivolumab + ipilimumab was studied in
patients with intermediate- or poor-risk
advanced RCC
• Extended follow-up (minimum 42
months) showed superiority of nivolumab
+ ipilimumab vs sunitinib:
‒ OS: 47.0 vs 26.6 months
‒ ORR: 42% vs 29% (CR: 12% vs 1%)
• In ITT patients, nivolumab + ipilimumab
showed improved efficacy compared with
sunitinib
CheckMate 214: Nivolumab + Ipilimumabvs Sunitinib as First-line Treatment
Tannir NM, et al. 2020 ASCO GU; Abstract 609.
OS in Intermediate-/Poor-Risk Disease
v
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
OS
(p
rob
ab
ility
)
Months
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
74%
60%
60%
47%
52%
39%
No. at risk
Nivolumab + ipilimumab
Sunitinib
19
Case Study (cont’d): Oliver
• Oliver agrees to begin axitinib and pembrolizumab for his advanced RCC
• Both Oliver and his family are educated on the treatment plan, mechanisms of
action of the drugs, and potential adverse effects of therapy
• He is instructed to take daily BP assessments at home and to call the office if he
develops hypertension, defined for this patient as 150/90 mm Hg
• He is to call the oncology provider if he develops any new symptoms
20
• Checkpoint inhibitors stimulate the immune
environment and can cause irAEs
• irAEs differ from AEs with chemotherapy and
targeted therapy
‒ Many occur within 2 to 3 treatment cycles,
but can occur any time—even after therapy
is discontinued
‒ Typically mild, but can be severe, irreversible,
or life-threatening
• irAEs do not occur in all patients
‒ Reasons are unknown
irAEs and Their Toxicity Spectrum
Brahmer JR, et al. J Clin Oncol. 2018;36:1714-1768; Cancer Council Victoria. www.cancervic.org.au/cancer-information/treatments/treatments-
types/immunotherapy. Accessed March 30, 2020; Postow MA, et al. N Engl J Med. 2018;378:158-168.
20
irAEs Can Affect Any Organ System
Encephalitis
Aseptic meningitis
Hypophysitis
Thyroiditis
Hypothyroidism
Hyperthyroidism
Pneumonitis
Hepatitis
Autoimmune
Diabetes
Pancreatitis
Thrombocytopenia
Anemia
Vasculitis
Neuropathy
Uveitis
Dry mouth
Mucositis
Myocarditis
Colitis
Enteritis
Rash
Vitiligo
Arthralgia
21
AE, % Any Grade (n = 429) Grade 3, 4, or 5 (n = 425)
AEs of any cause 98.4 75.8
Diarrhea 54.3 9.1
Hypertension 44.5 22.1
Fatigue 38.5 2.8
Hypothyroidism 35.4 0.2
Decreased appetite 29.6 2.8
Hand-foot-skin reaction 28.0 5.1
Nausea 27.7 0.9
ALT increased 26.8 13.3
AST increased 26.1 7.0
Dysphonia 25.4 0.2
Cough 21.2 0.2
Constipation 20.7 0
Most Common AEs (≥20%) Associated With Pembrolizumab + Axitinib Combination Treatment (n = 429)
ALT = alanine aminotransferase; AST = aspartate transaminase.
Rini BI, et al. N Engl J Med. 2019;380:1116-1127.
22
• Before starting treatment:
⎻ Educate patients about mechanisms of action and reasons for using combination treatment
⎻ Record all medications, including supplements and OTC medications
⎻ Provide patients with a wallet card outlining the type of treatments they are receiving, potential AEs, and
their care team contact numbers
⎻ Educate patients/caregivers about potential toxicity profiles, presenting symptoms, and timing of their treatments
⎻ Inform patients of educational resources
• Tell patients to notify the oncology healthcare team:
⎻ If any new signs or symptoms develop
• Monitor symptoms for at least 2 years after treatment has concluded
‒ When admitted to the hospital
‒ If any new medications are prescribed or prior to receiving any immunizations/vaccines
NCCN Guidelines. Management of immunotherapy-related toxicities. www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.
Accessed Mar 26, 2020.
Combination Therapy Patient Education
23
Case Study (cont’d): Oliver
• Front-line treatment with pembrolizumab 200 mg IV every 3 weeks and axitinib
5 mg twice a day was initiated, and a follow-up call 2 days later revealed no
adverse effects
• 8 days after initiation of cycle 3 of axitinib and pembrolizumab, Oliver called
with complaints of increasing fatigue, loss of appetite, difficulty with fluid intake,
and 5 loose stools in the past 24 hours (grade 2) despite maximum dosing of
loperamide
24
• Diarrhea is one of the most common side effects of axitinib
‒ For most cases, supportive care and use of antidiarrheals can control this toxicity
‒ For grade 3 or 4 diarrhea, reduce the axitinib dose or interrupt therapy until diarrhea
improves to grade 1
• When diarrhea occurs when axitinib is given in combination with pembrolizumab and can
be attributed to either drug, stop axitinib for a few days as an initial step
‒ Axitinib-induced toxicity should improve significantly with cessation of therapy due to its
short half-life
‒ Pembrolizumab-induced toxicity would not improve after stopping axitinib
• If diarrhea does not resolve with axitinib cessation and an irAE is suspected, follow the
appropriate guidelines
Managing Diarrhea Associated With Axitinib + Pembrolizumab
Greene HR. www.practiceupdate.com/content/management-of-diarrhea-associated-with-targeted-rcc-therapy/27360. Accessed Mar 26, 2020; Wood
LS, Ornstein MC. JCO Oncology Practice. 2020;16(2 suppl):15s-19s.
25
Guidelines for Managing irAEs
Brahmer JR, et al. J Clin Oncol. 2018;36:1714-1768; Postow MA, et al. N Engl J Med. 2018;378:158-168.
Toxicity Grade Recommendation
Grade 1 Continue checkpoint inhibitors with close monitoring, with exception of some neurologic, hematologic, and cardiac
toxicities
Grade 2
Hold for most grade 2 toxicities and consider resuming when symptoms and/or laboratory values return to
grade 1 or less
Corticosteroids (initial dose of 0.5 to 1 mg/kg/d of prednisone or equivalent) may be given
Grade 3
Hold checkpoint inhibitors for grade 3 AEs and initiate high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or
methylprednisolone IV 1 to 2 mg/kg/d)
• Taper corticosteroids over course of at least 4 to 6 weeks
• If symptoms do not improve with 48 to 72 hours of high-dose corticosteroid, infliximab may be offered for
some toxicities
Grade 4 Warrants permanent discontinuation of checkpoint inhibitors, with exception of endocrinopathies controlled by
hormone replacement
• When symptoms and/or lab values revert to grade 1 or less, rechallenging with checkpoint inhibitors may be offered. Use caution
when administering to patients with early-onset irAEs, and dose adjustments are not recommended.
26
• Dealing with two different mechanisms of action with two sets of AE profiles is
challenging
• Classical AEs of VEGF TKIs are fatigue, hypertension, diarrhea, oral pain, and
hand-foot-skin reaction
• Classical AEs of immunotherapy involve organ inflammation
• Notable crossover AEs: fatigue, diarrhea, hypothyroidism, LFT elevations
LFT = liver function test.
Rini BI, et al. N Engl J Med. 2019;380:1116-1127.
Monitoring Patients on Drugs With Different Mechanisms of Action
27TSH = thyroid stimulating hormone.
Case Conclusion: Oliver
• Oliver’s TSH increased from 3.4 at baseline to 13.0, and he was put on
levothyroxine
• Otherwise, he tolerated the combination of axitinib and pembrolizumab with no
other AEs except occasional diarrhea
• Imaging 3 months after start of treatment demonstrated regression of all lung
nodules and shrinkage of the primary renal mass
• The plan is to continue treatment for up to 2 years and take a break
28
Case Study 2: Margaret
• 72-year-old woman diagnosed with advanced clear-cell RCC and lung and liver
metastases
• She was treated 1st-line with axitinib + pembrolizumab
• After 3 months on treatment, her first follow-up scan showed marked progression
in her lung and local recurrence
• Her KPS was 70 and her risk score was 2 (intermediate)
29
• The novel multitargeted TKIs cabozantinib
and lenvatinib (combined with everolimus)
have shown favorable data in advanced RCC
‒ Cabozantinib is an inhibitor of multiple
receptor tyrosine kinases, including
VEGFR, MET, the TAM kinases, KIT, FLT3,
TRKB, and TIE2
‒ Lenvatinib is an inhibitor of VEGFR1–3,
FGFR1–4, PDGFRa, KIT, and RET
• Inhibiting these signaling molecules
contributes to the antitumor
immunomodulatory effect of these drugs
Tyrosine Kinase Inhibitors
Bergerot P, et al. Mol Cancer Ther. 2019;18:2185-2193; De Lisi D, et al. Expert Opin Drug Metab Toxicol. 2018;14:461-467.
Mechanism of Action of Multi-TKIs
Growth factor
signals to make
blood vessels
Receptor
Growth factor
signals for the
cell to divide
Receptor
Multi TKI
blocks
the signal
TKI going
into cell
30
Subsequent Therapy
Preferred regimens
• Cabozantinib (category 1)
• Nivolumab (category 1)
• Ipilimumab + nivolumab
Other recommended
regimens
• Axitinib (category 1)
• Lenvatinib + everolimus (category 1)
• Axitinib + pembrolizumab
• Everolimus
• Pazopanib
• Sunitinib
• Axitinib + avelumab (category 3)
Guidelines for Recurrent or Advanced Clear-Cell RCC: Subsequent Lines
NCCN Guidelines. Kidney cancer. www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed Mar 26, 2020.
31
100
80
60
40
20
0
• Multitargeted TKI lenvatinib was
approved in 2016 as combination
therapy with the mTOR inhibitor
everolimus for 2nd-line treatment of
advanced RCC
• Small randomized phase 2 study
with ~50 patients in each of 3 arms
• Median PFS vs everolimus
monotherapy: 14.6 vs 5.5 months
• Median OS vs everolimus: 25.5 vs
15.4 months
Lenvatinib + Everolimus
mTOR = mammalian target of rapamycin.
Lenvima [prescribing information]. Eisai Inc; 2020; Motzer RJ, et al. Lancet Oncol. 2015;16:1473-1482.
Pro
gre
ssio
n-f
ree S
urv
iva
l(%
)
Time (months)
0 3 6 9 12 15 18 21 24
Levatinib + everolimus
Single-agent lenvatinib
Single-agent everolimus
PFS by Treatment Group
32
• Multitargeted TKI approved in 2017 for front-line use in previously untreated RCC in
patients with intermediate/poor risk
‒ Approval based on results from the phase 2 CABOSUN trial
‒ Compared with sunitinib, cabozantinib reduced risk of progression or death by 52%
‒ Median PFS: 8.6 months vs 5.3 months with sunitinib
• Now approved for both 1st- and 2nd-line treatment of advanced RCC
• Toxicity profile of cabozantinib similar to other VEGFR TKIs for the treatment of
advanced RCC
‒ Most common grade 3 or 4 side effects were hypertension, diarrhea, and fatigue
Cabozantinib
Cabometyx [prescribing information]. Exelixis, Inc; 2020; Choueiri TK, et al. 2017 ESMO Congress. LBA38; Choueiri TK, et al. J Clin Oncol.
2017;35:591-597; Martinez Chanza N, et al. Lancet Oncol. 2019;20:581-590; US Food and Drug Administration.
www.fda.gov/drugs/informationondrugs/approveddrugs/ucm589842.htm. Accessed Mar 26, 2020
33
Case Study (cont’d): Margaret
• After 2 months of treatment with combination lenvatinib and everolimus, Margaret
begins to experience extreme fatigue
34
• Most common grade 1-2 TEAEs
reported in lenvatinib + everolimus
group
‒ Diarrhea, decreased appetite,
fatigue
• Most common TEAEs of grade ≥3 in
the lenvatinib + everolimus group
‒ Constipation, diarrhea, fatigue
• For toxicities thought to be related to everolimus alone, such as stomatitis and noninfectious
pneumonitis, the drug should be discontinued, interrupted, or used on alternate days, according to
the label
• For toxicities considered to be related to both lenvatinib and everolimus, the lenvatinib dose should
be reduced first
Toxicity Profile of Lenvatinib + Everolimus
TEAEs = treatment-emergent adverse events.
Afinitor [prescribing information]. Novartis Pharmaceuticals Corporation; 2020; Motzer RJ, et al. Lancet Oncol. 2015;16:1473-1482; Stenger M.
ascopost.com/issues/june-10-2016/lenvatinib-in-combination-with-everolimus-in-advanced-renal-cell-carcinoma/. Accessed Mar 26, 2020.
AE, %Lenvanitib +
EverolimusLenvanitib Everolimus
Diarrhea 65 60 32
Decreased appetite 45 54 18
Fatigue 45 42 36
35
Case Conclusion
• Eight months later, Margaret complained of fatigue, abdominal discomfort, and weight
loss; she subsequently developed back pain
• CT scan of abdomen and chest showed new liver lesions and progression of
previously identified lesions
• MRI of the spine showed multiple metastatic lesions of the thoracic and lumbar
vertebrae, with no evidence of cord compression
• She was switched to cabozantinib 60 mg and her symptoms subsided within 4 weeks
• She was maintained on cabozantinib for approximately 13 months until the disease
progressed
• Margaret is being considered for enrollment into a clinical trial
MRI = magnetic resonance imaging.
36
PCE Action Plan
✓ Be aware of patient factors that help determine the most appropriate therapy
options
✓ Provide patients with resource materials, reminders, and other tools (eg, wallet
cards) to reinforce details about toxicities related to combination therapy
✓ Consider rechallenge with checkpoint inhibitor therapy with caution in patients
whose irAE symptoms and/or laboratory values revert to grade ≤1
✓ It is important to discern causative therapy, since management of AEs is
dependent on differentiation
PCE Promotes Practice Change
2020 Spring Oncology Conference
