1. The History and Evolution of Immunotherapy in Renal Cell Carcinoma
In association with
The History and Evolution of Immunotherapy in Renal Cell Carcinoma
David F. McDermott, MD
Director, Biologic Therapy and Cutaneous Oncology Programs Beth Israel Deaconess Medical Center Leader, Kidney Cancer Program Dana-Farber Harvard Cancer Center Boston, Massachusetts
This program is supported by an educational grant from Bristol-Myers Squibb.

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Disclaimer: The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. Faculty Disclosure
David F. McDermott, MD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Genentech, Merck, Novartis, and Pfizer.
This slide lists the disclosure information of the faculty and staff involved in the development of these slides.
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4. Immunotherapy in Advanced RCC: A Renewed Level of Interest?
High-dose IL-2
Rise of the targeted therapies
Checkpoint inhibitors
Vaccines*
Recombinant T-cell receptors*
Bispecific T-cell engagers*
Level of Research
IFN-α and IL-2–based regimens
IFN, interferon; IL, interleukin; RCC, renal cell carcinoma.
Bevacizumab + IFN-α
< 1980s
*Not approved for metastatic RCC as of January 2016.
McDermott DF, et al. Semin Oncol. 2013;40: Figure adapted from L Harshman, MD
Slide credit: clinicaloptions.com

5. Mechanisms of Immune System Evasion/Suppression by Tumors
Inhibition of
tumor antigen
presentation
Inhibition of
immune cell attack through
checkpoint proteins
Tumor
eg, PD-L1 ↑
eg, MHC 1 ↓
eg, TGFβ ↑
MDSC, myeloid derived suppressor cells; MHC, major histocompatibility complex; TGFß, tumor growth factor ß; Treg, regulatory T cells.
Secretion of immunosuppressive factors
Recruiting of immunosuppressive cells (Treg, MDSC)
Drake CG, et al. Adv Immunol. 2006;90: Vesely MD, et al. Annu Rev Immunol. 2011;29:
Slide credit: clinicaloptions.com

6. Anti–PD-1: Blocking T-Cell Suppression+
Cytokines
Lysis
Tumor cell death
Activation
(cytokines, proliferation, migration)
B7-1
B7-2
T cell
Suppression
(anergy, exhaustion, T-cell death) -
PD-L1 +
CD28
APC or tumor cell
TCR
T cell
PD-L1
PD-1
Anti–PD-1 blockade
APC, antigen presenting cell; TCR, T cell receptor.
Reprinted with permission of Dove Medical Press, Ltd. from Srivastava N, McDermott, D. Cancer Manag and Res. 2014;6:
Slide credit: clinicaloptions.com

7. Key Late Stage Clinical Development of PD-1 Pathway Inhibitors
Agent
Target
Tumor Type
Clinical Development Stage
Nivolumab
PD-1
Melanoma, NSCLC, RCC
Approved (US)
Hodgkin’s lymphoma
Breakthrough Therapy (US)
Bladder/urothelial, brain, gastric/GEJ, HCC, HNSCC, SCLC
Phase III
Pembrolizumab
Melanoma, NSCLC
mCRC (MSI-high)
Breast, bladder/urothelial, gastric/GEJ, HNSCC, multiple myeloma
Atezolizumab
(MPDL3280A)
PD-L1
Bladder/urothelial, NSCLC
Breast, RCC
Durvalumab
(MEDI4736)
Bladder, NSCLC, HNSCC
Avelumab
Merkel cell
NSCLC, gastric, ovarian, urothelial
GEJ, gastroesophageal junction; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; mCRC, metastatic colorectal cancer; MSI, microsatellite instability; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma; SCLC, small-cell lung cancer.
Slide credit: clinicaloptions.com

8. PD-1/PD-L1 Checkpoint Inhibitors in Advanced RCC
RCC, renal cell carcinoma.

9. Clinical Activity of Nivolumab: Phase I Experience in Multiple Tumor Types
Dose, mg/kg
ORR (CR/PR), n (%)
SD ≥ 24 Wks, n (%)
Melanoma
104
0.1-10
26 (28)
6 (6)
NSCLC 76
1-10
14 (18)
5 (7)
RCC 33
1 or 10
9 (33)
9 (27)
28 responses (16 melanoma, 6 RCC, and 6 NSCLC) lasted ≥ 1 yr among 54 pts with treatment initiation ≥ 1 yr before data analysis
13 pts (4 melanoma, 6 NSCLC, 3 RCC) demonstrated nonconventional patterns of response but were not included as responders
NSCLC, non-small-cell lung cancer; ORR, objective response rate; RCC, renal cell carcinoma; SD, stable disease.
Slide credit: clinicaloptions.com
Topalian SL, et al. N Engl J Med. 2012;366:

10. Nivolumab in Previously Treated Advanced RCC: Phase I Expansion Cohort
ORR
Duration of Response
150
1 mg/kg nivolumab 10 mg/kg nivolumab
100
Responders
(per RECIST) 50
Best Tumor Burden Change (%)
-50 24 48 72 96
120
144
168
-100
Wks
RECIST, Response Evaluation Criteria in solid Tumors.
Pts
Time to and duration of response up to discontinuation of therapy
Response duration after discontinuation of therapy
Ongoing response
Time to response
Slide credit: clinicaloptions.com
McDermott DF, et al. J Clin Oncol. 2015;33:

11. Efficacy of Atezolizumab in Advanced RCC: Phase Ia Expansion Cohort
100
20 mg/kg 15 mg/kg 10 mg/kg 3 mg/kg 1200 mg 90 80 70 60 50 40 30 20
Maximum SLD Reduction From Baseline (%) 10
-10
-20
-30
-40
-50
-60
-70
-80
-90
-100
RCC, renal cell carcinoma; SLD, sum of longest diameters.
Clear-cell RCC (n = 62)
ORR: 15%
Median PFS: 5.6 mos
Median OS: 28.9 mos
Similar activity in VEGF-targeted therapy naive and refractory pts
Slide credit: clinicaloptions.com
McDermott DF, et al. J Clin Oncol. 2016;[Epub ahead of print].

12. CheckMate-025: Nivolumab in Previously Treated Metastatic RCC
Nivolumab 3 mg/kg IV every 2 wks
Metastatic RCC with ≤ 2 prior antiangiogenic therapies and ≤ 3 total prior systemic regimens
(N = 821)
Everolimus 10 mg PO daily
OR, overall response; RCC, renal cell carcinoma.
Primary endpoint: OS
Secondary endpoints: PFS, ORR, OR duration, Safety
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373:

13. CheckMate-025: OS
100
Median OS, Mos (95% CI)
Nivolumab (n = 410)
25.0 (21.8-NE)
Everolimus (n = 411)
19.6 ( ) 90 80
HR: 0.73 (98.5% CI: ; P = .0018) 70 60
OS (%) 50
Nivolumab 40
Everolimus 30 20
NE, not estimable. 10 3 6 9 12 15 18 21 24 27 30 33
Mos
Pts at Risk, n
Nivolumab
410
389
359
337
305
275
213
139 73 29 3
Everolimus
411
366
324
287
265
241
187
115 61 20 2
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 13

14. CheckMate-025: Response Characteristics
Nivolumab
Pts
On treatment
Everolimus
First response
Ongoing response
Off treatment 16 32 48 64 80 96
112
128
Wks
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 14

15. CheckMate-025: PFS
100 90
Median PFS, Mos
(95% CI)
Events, n
Nivolumab
4.6 ( )
318
Everolimus
4.4 ( )
322 80 70 60
PFS (%) 50
HR (95% CI), 0.88 (0.75–1.03); P = 40 30
Nivolumab 20 10
Everolimus
PFS, progression-free survival. 3 6 9 12 15 18 21 24 27 30
Mos
Pts at Risk, n
Nivolumab
410
230
145
116 81 66 48 29 11 4
Everolimus
411
227
129 97 61 47 25 16 3
Median PFS was 15.6 mos (nivolumab, 95% CI: ) vs 11.7 mos (everolimus, 95% CI: ) (HR: 0.64; 95% CI: ) by a sensitivity analysis in pts who had not progressed or died at 6 mos
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 15

16. Toxicities Associated With PD-1/PD-L1 Checkpoint Inhibitors

17. CheckMate-025: Treatment-Related AEs (≥ 10% of Pts)
Nivolumab
(n = 406)
Everolimus
(n = 397)
Any Grade
Grade 3/4
Treatment-related AEs 79 19 88 37
Fatigue 33 2 34 3
Nausea 14
< 1 17 1
Pruritus 10
Diarrhea 12 21
Decreased appetite
Rash 20
Cough 9
Anemia 8 24
Dyspnea 7 13
Edema peripheral 4
Pneumonitis 15
Mucosal inflammation
Dysgeusia
Hyperglycemia
Stomatitis 29
Hypertriglyceridemia 16 5
Epistaxis
AE, adverse event.
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 17

18. PD-1/PD-L1 Inhibition: Managing Treatment-Related AEs
Any grade 1 AE Isolated hypothyroidism
Grade 2 pneumonitis, nephritis, colitis, hepatitis Symptomatic hypophysitis
Any grade 3 AE
Initiate steroids or replacement therapy for hypothyroidism
Hold PD-1 tx and administer steroids
After improvement to grade ≤ 1, taper steroids over at least 1 mo
AE, adverse event; tx, treatment.
Continue PD-1 tx and monitor
Resume if:
AE remains at grade 0/1 after steroid taper
Discontinue if:
No improvement to grade ≤ 1 within 12 wks
Pembrolizumab adverse reaction management guide. Nivolumab adverse reaction management guide.
Slide credit: clinicaloptions.com

19. PD-1/PD-L1 Inhibition: Managing Treatment-Related AEs
Grade 3/4 pneumonitis
Grade 3/4 nephritis
Grade 3/4 infusion-related reaction
Any life-threatening or grade 4 AE
Any severe or grade 3 recurrent AE
Initiate steroid therapy
Hepatitis associated with
AST/ALT > 5 x ULN
AST/ALT ≥ 50% ↑ from baseline lasting ≥ 1 wk*
Total bilirubin > 3 x ULN
Permanently discontinue PD-1 tx
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; tx, treatment; ULN, upper limit of normal.
*In pts with liver metastasis who begin treatment with grade 2 elevation of AST/ALT.
Pembrolizumab adverse reaction management guide. Nivolumab adverse reaction management guide.
Slide credit: clinicaloptions.com

20. CheckMate-025: Change From Baseline in QoL Scores
A clinically meaningful and statistically significant improvement in QoL was seen with nivolumab vs everolimus for the duration of the study
Questionnaire completion rate: ≥ 80% during the first yr of follow-up 6
Nivolumab 4 2
Better
FKSI-DRS: Mean Change From Baseline -2
Worse
FKSI-DRS, Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms; QoL, quality of life. -4
Everolimus -6 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96
100
104
Wks
Pts at Risk, n
Nivolumab
362
334
302
267
236
208
186
164
159
144
132 1 19 1 12 97 90 89 81 72 63 59 53 44 43 31 30 26 20
Everolimus
344
316
270
219
191
157
143
122
102 97 87 74 73 63 58 49 44 35 30 28 24 21 15 12 12 9 9
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 20

21. PD-L1 Expression and Patient Selection in Advanced RCC
RCC, renal cell carcinoma.

22. Relevance of Tumor PD-L1 Expression in RCC
Tumoral PD-L1 expression may be associated with:
Impaired antitumor immunity
More aggressive disease
High tumor grade
Shorter survival
100
PD-L1 expression < 10% 80
PD-L1 expression ≥ 10% 60
Cancer-Specific Survival 40 20
RCC, renal cell carcinoma. 1 2 3
Yrs From Nephrectomy to Last Follow-up
Thompson RH, et al. Proc Natl Acad Sci USA. 2004;101:
Thompson RH, et al. Clin Cancer Res. 2007;13:
Krambeck AE, et al. Clin Cancer Res. 2007;13:
Frigola X, et al. Clin Cancer Res. 2011;17:
Slide credit: clinicaloptions.com 22

23. PD-L1 Expression Is a Poor Predictive Biomarker of Tumor Response
Agent(s)
Tumor Type n RR
PD-L1 Pos, %
PD-L1 Neg, %
Nivolumab[1]
Multiple solid tumors 42 36
Atezolizumab[2]
Kidney cancer 55 18 9
Nivolumab[3]
Melanoma
210
52.7
33.1
Nivolumab/ ipilimumab[4]
278
72.1
54.8
Neg, negative; Pos, positive; RR, relative risk.
1. Topalian SL, et al. N Engl J Med. 2012;366:
2. McDermott DF, et al J Clin Oncol. 2016;[Epub ahead of print].
3. Robert C, et al. N Engl J Med. 2015;372:
4. Larkin J, et al. N Engl J Med. 2015;373:23-34.
Slide credit: clinicaloptions.com

24. CheckMate-025: OS by PD-L1 Expression
Median OS, Mos (95% CI)
Nivolumab
21.8 ( )
Everolimus
18.8 ( )
Median OS, Mos (95% CI)
Nivolumab
27.4 (21.4-NE)
Everolimus
21.2 (17.7–26.2) 3 6 12 9 15
Mos 18 21 24 27 30 33 10 20 40 50 60 70 80 90
100
OS (%) 3 6 12 9 15
Mos 18 21 24 27 30 33 10 20 40 50 60 70 80 90
100
HR: (95% CI: )
HR: (95% CI: )
Nivolumab
Nivolumab
Everolimus
Everolimus
NE, not estimable.
Pts at Risk, n
Nivolumab 94 86 79 73 66 58 45 31 18 4 1
276
265
245
233
210
189
145 94 48 22 2
Everolimus 97 77 68 59 52 47 40 19 9 4 1
299
267
238
214
200
192
137 92 51 16 1
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 24

25. Current Management of Advanced ccRCC
First-line Therapy
Second-line Therapy
Favorable or
intermediate risk
Sunitinib or pazopanib or bevacizumab + IFN*
(or other TKI, HD IL-2, or temsirolimus)
Axitinib, nivolumab, cabozantinib†, or everolimus (after TKI)
(or other TKI, temsirolimus, or
bevacizumab)
Axitinib, sorafenib, sunitinib, or
pazopanib (after cytokine)
(or temsirolimus or bevacizumab)
Poor risk
Temsirolimus
or sunitinib or pazopanib
Unknown
(clinical trial, supportive care)
ccRCC, clear-cell renal cell carcinoma; HD IL-2, high-dose interleukin 2; IFN, interferon; TKI, tyrosine kinase inhibitor.
*Category 1 recommendations in bold.
†Based on phase III study data. Not approved as of January 18, 2016.
Slide credit: clinicaloptions.com
NCCN. Clinical practice guidelines in oncology: kidney cancer. v

26. Future Opportunities for Patient Selection

27. Atezolizumab in Advanced RCC: Preliminary ORR in Pt Subgroups
ORR, n (%)
No previous VEGFR TKI (n = 24)
3 (13)
Previous VEGFR TKI (n = 38)
6 (16)
Fuhrman grade 4 and/or sarcomatoid histology (n = 18)
4 (22)
Fuhrman grade 4 (n = 16)
4 (25)
Sarcomatoid histology (n = 6)
2 (33)
MSKCC poor risk (n = 20)
5 (25)
MSKCC intermediate/favorable risk (n = 42)
4 (10)
MSKCC, Memorial Sloan Kettering Cancer Center; ORR, overall response rate; Pt, patient; RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor.
Slide credit: clinicaloptions.com
McDermott DF, et al. J Clin Oncol. 2016;[Epub ahead of print].

28. CheckMate-025: Exploratory Analysis of OS by Subgroup
Nivolumab,
n/N
Everolimus,
Overall
183/410
215/411
MSKCC
Favorable
45/145
52/148
Intermediate
101/201
116/203
Poor
37/64
47/60
Prior antiangiogenic regimens 1
128/294
158/297 2
55/116
57/114
Region
US/Canada
66/174
87/172
Western Europe
78/140
84/141
Rest of the world
39/96
44/98
Age, yrs
< 65
111/257
118/240
≥ 65 to < 75
53/119
77/131
≥ 75
19/34
20/40
Sex
Female
48/95
56/107
Male
135/315
159/304
MSKCC, Memorial Sloan Kettering Cancer Center.
0.25
0.5
0.75 1
1.5
2.25
Favors nivolumab
Slide credit: clinicaloptions.com
Motzer R, et al. N Engl J Med. 2015;373: 28

29. Combination Therapy: Overcoming Innate/Acquired Resistance

30. Strategies to Optimize Immunotherapy Benefit in the Clinic
Inflamed tumor phenotype (TIL+, PD-L1+)
PD-1/PD-L1
monotherapy
Tolerant tumor phenotype (TIL+, PD-L1-)
PD-1/PD-L1
combination therapy
Anti-VEGF
Cytokines
IDO inhibitors
Other checkpoint inhibitors
IDO, indoleamine 2,3-dioxygenase 1; TIL, tumor infiltrating lymphocytes.
Slide credit: clinicaloptions.com

31. Change in SLD From Baseline (%)
Phase Ib Study of Atezolizumab + Bev: First-line Therapy for Advanced ccRCC
Atezolizumab 20 mg/kg + Bev 15 mg/kg q3w
Safety
Treatment-related grade 3 AEs occurred in 3% of pts (1 case of neutropenia)
No grade 4 AEs or deaths were attributed to atezolizumab
Efficacy (n = 10)
ORR: 40%
IC 1 (2 pts), 1 pt each IC 0 or IC unknown
SD ≥ 24 wks: 50%
IC 3: ≥ 10% PD-L1+
IC 2: 5% to < 10% PD-L1+
IC 1: 1% to < 5% PD-L1+
IC 0: < 1% PD-L1+.
100 80 60
IC 3 40 20
IC 1
IC 0
IC 1
Change in SLD From Baseline (%)
IC 0
-20
IC 0
-40
IC 1
IC 1
-60
IC 0
AE, adverse event; Bev, bevacizumab; IC, immune cell; SD, stable disease; SLD, sum of longest diameters.
-80
-100 42 84
126
168
210
252
Days on Study
Slide credit: clinicaloptions.com
Lieu C, et al. ESMO Abstract 1049O.

32. Nivo + Sun; Nivo + Paz; Nivo + Ipi at 3 different dose combinations*
Ongoing Trials of PD-1 + VEGF Pathway Blockade as First-line Therapy in Advanced RCC
Study
Phase (Number of Pts)
Treatment
Status
Nivolumab
NCT
I (175)
Nivo + Sun; Nivo + Paz; Nivo + Ipi at 3 different dose combinations*
Closed to accrual
Pembrolizumab
NCT
I/II (228)
Pem±Paz
Recruiting
NCT
Ib (60)
Pem + Axi
NCT
Ib/II (61)
Pem + Bev
Atezolizumab
NCT (IMmotion150)
II (305)
Atezo± Bev vs Sun
NCT (IMmotion151)
III (830)
Atezo + Bev vs Sun
Avelumab
NCT
Ib (55)
Avel + Axi
Atezo, atezolizumab; Avel, avelumab; Axi, axitinib; Bev, bevacizumab; Ipi, ipilimumab; Nivo, nivolumab; Paz, pazopanib; Pem, pembrolizumab; RCC, renal cell carcinoma; Sun, sunitinib.
*Previous systemic therapy for metastatic disease allowed for SUN and PAZ combination arms.
Slide credit: clinicaloptions.com
Clinicaltrials.gov.

33. CheckMate-016: Phase I Study of Nivolumab + Ipilimumab in mRCC
Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV q3w x 4 doses
(n = 47)
mRCC; no previous systemic therapy other than cytokine therapy for mRCC or 1 prior adjuvant/neoadjuvant therapy with recurrence ≥ 6 mos after last treatment
(N = 100)
Nivolumab
3 mg/kg IV
q2w
Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg IV q3w x 4 doses
(n = 47)
Nivolumab 3 mg/kg + Ipilimumab 3 mg/kg IV q3w x 4 doses
(n = 6)
DoR, duration of response; mRCC, metastatic renal cell carcinoma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
Primary endpoint: Safety
Secondary endpoints: ORR, DoR, PFS, OS
Slide credit: clinicaloptions.com
Hammers H, et al. ASCO Abstract 4516.

34. CheckMate-016: Response Outcomes
Tumor Response, n (%)
Nivo 3 mg/kg + Ipi 1 mg/kg
(n = 47)
Nivo 1 mg/kg + Ipi 3 mg/kg
Nivo 3 mg/kg + Ipi 3 mg/kg
(n = 6)
ORR
18 (38.3)
19 (40.4) CR
4 (8.5)
1 (2.1) PR
14 (29.8) SD
17 (36.2)
5 (83.3)
Median duration of response:
Nivolumab 3 mg/kg + ipilimumab 1 mg/kg: 67.7 wks (range: )
Nivolumab 1 mg/kg + ipilimumab 3 mg/kg: 81.1 wks (range: )
CR, complete response; Ipi, ipilimumab; Nivo, nivolumab; ORR, overall response rate; PR, partial response; SD, stable disease.
Slide credit: clinicaloptions.com
Hammers H, et al. ASCO Abstract 4516.

35. CheckMate-016: Select Treatment-Related AEs
AE, n (%)
Nivo 3 mg/kg + Ipi 1 mg/kg
(n = 47)
Nivo 1 mg/kg + Ipi 3 mg/kg
Nivo 3 mg/kg + Ipi 3 mg/kg (n = 6)
Any Grade
Grade 3/4
Skin disorder
18 (38.3)
24 (51.1)
1 (2.1)
3 (50.0)
GI disorder
11 (23.4)
21 (44.7)
2 (33.3)
Endocrinopathy
20 (42.6)
5 (83.3)
Hepatic
7 (14.9)
2 (4.3)
15 (31.9)
10 (21.3)
Renal disorder
5 (10.6)
Infusion reaction
4 (8.5)
3 (6.4)
1 (16.7)
Pulmonary
AE, adverse event; GI, gastrointestinal; Ipi, ipilimumab; Nivo, nivolumab.
Select AEs defined as AEs with potential immune-mediated etiology that may require special monitoring and specific unique interventions.
Slide credit: clinicaloptions.com
Hammers H, et al. ASCO Abstract 4516.

36. CheckMate-214: Nivo + Ipi vs Sunitinib as First-line Therapy for Advanced RCC
Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV q3w for 4 doses,
followed by Nivolumab 3 mg/kg IV q2w
Advanced/metastatic clear-cell RCC with no prior systemic therapy
(N  1070)
Sunitinib 50 mg PO QD
4 wks on/2 wks off
Ipi, ipilimumab; Nivo, nivolumab; RCC, renal cell carcinoma.
Primary endpoint: PFS, OS
Secondary endpoints: ORR, safety
Slide credit: clinicaloptions.com
ClinicalTrials.gov. NCT

37. Strategies to Optimize Immunotherapy Benefit in the Clinic
Inflamed tumors
(TIL+, PD-L1+)
PD-1/PD-L1
monotherapy
PD-1/PD-L1 combination therapy
Anti-VEGF
Cytokines
IDO inhibitors
Other checkpoint inhibitors
Tolerant tumors
(TIL+, PD-L1-)
IDO, indoleamine 2,3-dioxygenase 1; TIL, tumor infiltrating lymphocytes.
PD-1/PD-L1 combination therapy
Vaccines
Engineered T cells
Noninflamed tumors
(TIL-, PD-L1-)
Slide credit: clinicaloptions.com

38. Conclusions
Single-agent PD-1 pathway blockade is efficacious in advanced RCC
Nivolumab is approved for pts following progression on antiangiogenic therapy
Vigilance for irAEs by the entire healthcare team and well- educated pts along with rapid intervention is key to optimal management
Biomarkers that predict response are being investigated
Tumor grade and mutational load may add value
Combination regimens appear to improve outcomes at a cost of increased toxicity
Management algorithms will need to be refined
Vaccine strategies likely need more work
irAE, immunotherapy-related adverse event; RCC, renal cell carcinoma.
Slide credit: clinicaloptions.com

39. Go Online for More CCO Coverage of RCC!
Additional CME-certified text module on immunotherapy for advanced RCC Online Decision Support Tool showing treatment choices of 5 experts based on specific patient characteristics
clinicaloptions.com/oncology