Oncology Conference Raising the Bar for the Standard of Care: - - PowerPoint PPT Presentation

2020 Spring Oncology Conference

Raising the Bar for the Standard of Care: Advances in the Management of Advanced Renal Cell Carcinoma

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• 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

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• 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.

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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 (Confined to Primary Site) Regional (Spread to Regional Lymph Nodes) Distant (Cancer Has Metastasized) Unknown (Unstaged) 92.5% 69.6% 12.0% 41.9% 0% 20% 40% 60% 80% 100%

Percent Surviving Stage

5-Year Relative Survival

Localized Regional Distant Unknown

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• 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.

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• 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.

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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.

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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 Intermediate 1-2 Poor 3-6

• Current FDA indications restrict certain treatments based on these risk categories

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• 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.

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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

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• 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-

• ncology/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 MHC TCR MHC CD28 B7 Anti- CTLA-4 CTLA-4 Renal cancer cell Antigen-presenting cell T cell

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• 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-VEGF

VEGF TKI Anti-PD-1 Anti-PD-L1 VEGF/R Myeloid DCs PD-1 PD-L1

CD3 CD3 CD4 CD3 APC Treg MDSCs Macrophage (M2 phenotype) Tumor

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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.

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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.

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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

Patients Who Were Alive (%) Months

Pembrolizumab + axitinib Sunitinib 100 90 80 70 60 50 40 30 20 10 Hazard ratio for death, 0.53 (95% CI, 0.38-0.74) P <0.0001

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• 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 + Axitinib vs 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

PFS (%)

2 4 6 8 10 12 14 16 18 20 22 24

Months

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• 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 + Ipilimumab vs 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 (probability) Months

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

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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

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• 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,

• r 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.

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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

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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

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.

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• 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

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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

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• 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.

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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.

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• 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

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TSH = 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
• ther 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

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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)

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• 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

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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.

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100 80 60 40 20

• 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.

Progression-free Survival(%) Time (months)

3 6 9 12 15 18 21 24 Levatinib + everolimus Single-agent lenvatinib Single-agent everolimus

PFS by Treatment Group

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• 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

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Case Study (cont’d): Margaret

• After 2 months of treatment with combination lenvatinib and everolimus, Margaret

begins to experience extreme fatigue

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• 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 + Everolimus Lenvanitib

Everolimus

Diarrhea 65 60 32 Decreased appetite 45 54 18 Fatigue 45 42 36

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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.

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PCE Action Plan

✓ Be aware of patient factors that help determine the most appropriate therapy

• ptions

✓ 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