NEW TREATMENTS IN GU MALIGNANCIES

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1 NEW TREATMENTS IN GU MALIGNANCIES Daniel George, MD Professor of Medicine and Surgery Director of Genitourinary Oncology Program Duke Cancer Institute 1

2 Disclosures Consultant: Astellas, Bayer, BMS, Clovis, Dendreon, Exelixis, Genentech/Roche, Innocrin, Medivation, Merck, Novartis, Pfizer, Sanofi Research Support: Acerta, Astellas, Bayer, Exelixis, Innocrin, Janssen, Novartis, Pfizer Speaker: Dendreon, Novartis, Sanofi Steering Committees: Pfizer, NCI DMC: Acceleron, Janssen 2

3 Kidney Cancer what s new? Sunitinib improves DFS in adjuvant setting Cabozantinib improves PFS compared to sunitinib in intermediate/poor risk mrcc Novel immunotherapy combinations in development for first line RCC 3

4 Abstract ID: 2632 Phase III trial of sunitinib versus placebo as adjuvant treatment for high-risk renal cell carcinoma after nephrectomy (S-TRAC) Alain Ravaud 1, Robert J Motzer 2, Hardev S Pandha 3, Michael Staehler 4, Daniel J George 5, Allan J Pantuck 6, Anup Patel 7, Yen-Hwa Chang 8, Bernard Escudier 9, Frede Donskov 10, Ahmed Magheli 11, Giacomo Carteni 12, Brigitte Laguerre 13, Piotr Tomczak 14, Jan Breza 15, Paola Gerletti 16, Mariajose Lechuga 16, Xun Lin 17, Jean-Francois Martini 17, Jean-Jacques Patard 18 1 Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; 2 Memorial Sloan Kettering Cancer Center, Department of Oncology, New York, NY, USA; 3 University of Surrey, Department of Microbial Sciences, Surrey, UK, 4 University Hospital of Munich, Department of Urology, Munich, Germany; 5 Duke Cancer Center, Division of Oncology, Durham, NC, USA; 6 Department of Urology, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA, 7 Spire Roding Hospital, London, UK; 8 Taipei Veterans General Hospital, Department of Urology, Taipei, Taiwan; 9 Institut Gustave Roussy, Department of Medical Oncology, Villejuif, France; 10 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 11 Charité Universitaetsmedizin Berlin, Department of Urology, Berlin, Germany; 12 Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Division of Oncology and Division of Urology, Naples, Italy; 13 Centre Eugene Marquis, Medical Oncology, Rennes, France; 14 Klinika Onkologii Oddzial Chemioterapii, Poznan, Poland; 15 Slovak Medical University in Bratislava, Department of Urology, Bratislava, Slovakia; 16 Pfizer S.r.L, Milan, Italy; 17 Pfizer Inc, La Jolla, CA, USA; 18 Department of Urology, Bicêtre Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France esmo.org

5 Background (II) qcytokine therapy, hormone therapy, immune therapy, and radiotherapy for adjuvant treatment in RCC were unsuccessful 1 qassure trial compared sunitinib and sorafenib with placebo as adjuvant therapy in patients with intermediate- and high-risk RCC with no success 2 1. Janowitz T, et al, Semin Oncol Haas NB, et al, Lancet Oncol

6 Study Design High Risk (T3+) Clearcell RCC Stratified by UISS risk groups ECOG PS (<2 vs 2) Country N=600 (planned) N=615 (accrued) R A N D O M I S A T I O N 1:1 Sunitinib 50 mg/day orally, 4/2 schedule* Placebo 50 mg/day orally, 4/2 schedule* * Dose reduction only to 37.5 mg/day allowed. 6 6

7 615 patients enrolled between September 2007 and April 2011 Baseline Characteristics Sunitinib n=309 Placebo n=306 Characteristics Age, median (range), years 57.0 (25 83) 58.0 (21 82) Male / Female, % 71.8 / / 25.2 Baseline ECOG PS, % Unknown Clear cell/non-clear cell, % 99.0/ /0 UISS risk groups, % T3 low* T3 high T4 N0 or NX Any T, N * N0 or NX, Any Fuhrman s grade, ECOG PS 0 or Fuhrman's grade 1, ECOG PS 1. N0 or NX, Fuhrman s grade 2, ECOG PS 1. Any Fuhrman s grade, any ECOG PS. 7 7

8 Patient Disposition and Treatment Dosing Information Sunitinib n=306 Placebo n=304 Treatment duration*, median (range), months ( ) ( ) Treatment completion, % Treatment discontinuation, % Reasons for discontinuation, % Adverse events Disease progression/relapse Other Dose reductions, n (%) Dose interruptions, n (%) Relative dose intensity, median (range) 88.4 ( ) 99.7 ( ) * Duration of treatment was defined as the period between first and last doses of the drug and included interruptions, cycle delays, and the scheduled 2-week off treatment. Investigators had to select only one reason. 8 8

9 Disease-Free Survival By Blinded Independent Central Review Proportion Disease-Free 3-year DFS rate: 64.9% 59.5% 5-year DFS rate: 59.3% 51.3% P=0.030* Disease-Free Survival (years) * Two-sided P value from log-rank test stratified by UISS high-risk group. 9 9

10 Conclusions (I) q Adjuvant treatment with sunitinib prolonged disease-free survival (HR, 0.761; 95% CI, ; P=0.030) in patients with high-risk, loco-regional clear-cell RCC q The effect of 1-year adjuvant treatment was sustained over time: more sunitinib-treated patients were event-free at 3 years (5.4%) and 5 years (8%) vs placebo-treated patients q Overall survival at data cut-off were not mature 10 10

11 NCCN Guidelines for First Line Treatment of mrcc Clinical Trial, or Pazopanib (category 1, preferred), or Sunitinib (category 1, preferred), or Bevacizumab plus INF (category 1), or Temsirolimus (category 1 for poor-risk patients, category 2B for selected patients of other risk groups), or Axitinib (category 2A), or High dose IL-2 (category 2A for selected patients), or Sorafenib (category 2A for selected patients), and Best supportive care Version /3/16 NCCN 11

12 Cabozantinib Cabozantinib is an oral small molecule inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL 1 In the randomized phase 3 METEOR trial, cabozantinib improved PFS, OS and response rate compared to everolimus in RCC patients after VEGFR TKI therapy 2 FDA-approved in April 2016 and EMA-approved in September 2016 The CABOSUN study evaluated cabozantinib compared to sunitinib in previously untreated poor and intermediate risk RCC patients Clinical Trials.gov identifier: NCT Yakes FM et al., Mol Cancer Ther, Choueiri TK et al., NEJM 2015 and Lancet Oncol,

13 Cabosun Study Design Advanced RCC (N=150) Clear cell component Measurable disease No prior systemic therapy ECOG PS 0-2 IMDC intermediate or poor risk groups Stratification: IMDC risk group 1 : intermediate, poor Bone metastases: yes, no Cabozantinib 60 mg qd orally (6 week cycles) Randomization 1:1 No cross-over allowed Sunitinib 50 mg qd orally (4 weeks on/2 weeks off) Tumor assessment by RECIST 1.1 every other cycle Treatment until disease progression or intolerable toxicity 1 Heng D et al., J Clin Oncol, Choureiri et al JCO 13

14 Baseline Characteristics (N=157) Characteristic Cabozantinib (N=79) Sunitinib (N=78) Median age, years (range) 63 (40-82) 64 (31-87) Male, % ECOG performance status, % IMDC risk group 1, % Intermediate Poor Prior nephrectomy, % Bone metastases, % Adverse risk factors 1 : Intermediate risk group Poor-risk group hemoglobin<lln, cca>uln, KPS<80%, neutrophils>uln time from diagnosis to therapy <1 year, platelets>uln 1-2 risk factors 3 or more risk factors 1 Heng, Xie and Choueiri et al., J Clin Oncol,

15 Progression-free Survival Arm PFS Events Median PFS (95% CI), mo HR (95% CI)* Cabozantinib Sunitinib (6.2, 9.0) 5.6 (3.4, 8.1) 0.66 ( ) p-value (one-sided) = Choureiri et al JCO 2016

16 Objective Responses Choureiri et al JCO 16

17 Overall Survival Arm Deaths Median Survival (95% CI), mo HR (95% CI)* Cabozantinib Sunitinib (14.6, 35.0) 21.8 (16.3, 27.0) 0.80 (0.50, 1.26) 17 Choureiri et al JCO

18 Pre-specified Subgroup Analyses 18 Choureiri et al JCO

19 All-Causality Adverse Events Cabozantinib (N=78) Sunitinib (N=72) Preferred Term, % All Grades Grade 3/4 All Grades Grade 3/4 Any adverse event* Fatigue Hypertension Diarrhea AST increased ALT increased Anorexia PPE Dysgeusia Thrombocytopenia Oral mucositis Anemia Nausea Weight loss Neutropenia Leukopenia * Events reported in at least 30% of patients in either study group; PPE, palmar-plantar erythrodysesthesia Choureiri et al JCO

20 CABOSUN Study Conclusions Cabozantinib significantly improves PFS compared to sunitinib in previously-untreated RCC patients of intermediate- and poor-risk IMDC categories: 8.2 vs. 5.6 months (HR=0.69, one-sided p=0.012) Benefit from cabozantinib was seen across subgroups Cabozantinib improves ORR over sunitinib ORR: 46% vs 18% Emerging trend towards improved OS with cabozantinib (HR=0.80, ns) Cabozantinib's safety profile was similar to sunitinib Cabozantinib represents a potential new treatment option for untreated RCC patients 19 20

21 Ongoing Phase III Studies WO29637 atezolizumab + bevacizumab vs sunitinib Checkmate 214 ipilimumab + nivolumab vs sunitinib Keynote 426 pembrolizumab + axitinib vs sunitinib Eisai lenvantinib + pembrolizumab vs lenvantinib + everolimus vs sunitinib Javelin Renal 101 avelumab and axitinib vs sunitinib 21

22 Key Takeaways Adjuvant sunitinib for some patients, clinical trial options for others Not all TKIs are the same Cabozantinib is superior to sunitinib in intermediate/poor risk patients Combinations with Ipi/Nivo or VEGF TKI and anti-pd-1/pdl-1 therapy may replace VEGF TKI alone 22

23 Prostate cancer what s new? Wide variation in practice patterns Sipuleucel-T use Abiraterone vs Enzalutamide Timing of Chemotherapy and Radium Biology of AR V-7 variants Biology of DNA damage repair genes Rationale for PARP inhibitors 23

24 NCCN Schema: M1 CRPC Prostate Cancer NCCN guidelines. v

25 Multiple Treatment Options Are Now Available for Men With Metastatic Prostate Cancer Tumor Volume and Activity Natural History of Lethal Prostate Cancer and Treatment Options Local Therapy Nonmetastatic Castration Hormone Therapy NONMETASTATIC Asymptomatic Sipuleucel-T Abiraterone or Enzalutamid e Time Metastatic Docetaxel Radium-223 Symptomatic Cabazitaxel Radium

26 IMPACT Study: Sipuleucel-T vs Placebo Overall Survival Adverse Events Percent Survival P=0.032 (Cox model) HR=0.775 (95% CI: ) Median survival benefit=4.1 mo Sipuleucel-T (n=341) Median survival: 25.8 mo Adverse Event Sipuleucel-T (n=601) (%) All Grades* Control (n=303) (%) Chills Fatigue Fever Back pain Nausea Joint ache Headache Survival (months) Kantoff PW, et al. N Engl J Med. 2010;363:

27 Trend Toward Greater Survival Benefit with Lower Baseline PSA Baseline PSA (ng/ml) 22.1 (n=128) > (n=128) > (n=128) >134.1 (n=128) Median OS (mos) Sipuleucel-T Control Difference HR (95% CI) 0.51 (0.31, 0.85) 0.74 (0.47, 1.17) 0.81 (0.52, 1.24) 0.84 (0.55, 1.29) Schellhammer PF et al. Urology. 2013;81:

28 The Case for Enzalutamide or Abiraterone Prednisone FDA-approved therapy PSA response, radiographic PFS and OS advantage seen in two independent Ph3 studies Oral daily use Low grade toxicity profile Broad coverage by payers 28

29 Enzalutamide and Abiraterone in Chemo-naïve mcrpc Overall survival rpfs OS 30.2à34.7 mo HR 0.81 p= Beer TM, et al. N Engl J Med. 2014;371: Ryan CJ, et al. Lancet Oncol. 2015;16: Ryan CJ, et al. N Engl J Med. 2012;368:

30 Enzalutamide Adverse Events Beer TM, Armstrong AJ, et al. N Engl J Med. 2014;371:

31 Abiraterone acetate side effects Ryan CJ, et al. Lancet Oncol. 2015;16:

32 Abiraterone vs. Enzalutamide in Chemotherapy Naïve Men with mcrpc Abiraterone Acetate Enzalutamide Requires prednisone Y N May cause mineralocorticoid excess Evaluated in visceral disease Y (post-chemo only) Y (pre/post chemo) Major side effects Y Hypertension, hypokalemia, LFTs, edema, some cardiac, fatigue, hot flush N Hypertension, rare seizures (<0.2%), some cardiac, fatigue, falls (19%), hot flush Grade 3-4 AE Risk (%) 48% 43% PSA response rate (>50%) 62% 78% Radiographic response rate 36% 59% rpfs 16.5 months months OS 34.7 months 35.3 months Time to chemotherapy 25 months 28 months Zhang T, Armstrong et al. Exp Opin Pharmacother. 2015;16:

33 Androgen Receptor (AR) Variants and Abiraterone / Enzalutamide Resistance AR-FL AR-V7 14% V7 conversions over time, poor outcome Primary Resistance: prevalence of V7 likely depends on setting, prior therapy Antonarakis E, et al. New Engl J Med. 2014;371:2234. Acquired resistance: unknown at this time 33

34 AR-V7 increases with Disease Progression Scher, et al. JAMA Oncol [Epub ahead of print] 34

35 Cross-Resistance in the Clinic Enzalutamide after abiraterone can result in PSA responses (>50% decline) but this was observed in <1/3 of men in the post-docetaxel CRPC setting with a short TTP of 4 months and rare radiographic responses Similar for abi after enza and in pre-docetaxel setting Response to enzalutamide was not possible to predict based on prior response to abiraterone Schrader AJ. Eur Urol. 2014;65: Zhang, T, Armstrong AJ, et al. Clin Genitourin Cancer. 2015;13:

36 Defects in DNA repair genes associated with PARP inhibitor sensitivity Mateo J et al. New Engl J Med. 2015;373: heavily pretreated mcrpc men PARP inhibitor (olaparib 400 mg BID) Genomic signature of PARP inhibitor sensitivity in 16/49 (33%) BRCA2, ATM, BRCA1, PALB2, CHEK2, FANCA, HDAC2 Response to PARP in 14/16 36

37 Hereditary DNA repair defects in mcrpc Prevalence of 11.8% germline defects in mcrpc pts, predominantly in BRCA2, ATM, CHEK2, BRCA1, PALB2; Family history of GI, breast, pancreatic, melanoma cancers 37 NCCN 2017, Pritchard CC et al NEJM 2016

38 Median Progression To Symptomatic Disease on Prevail (11 months) CLINICAL PROGRESSION Presence of symptoms associated with bone metastases Fatigue, generalized weakness 2 Interference with sleep 3 Dyspnea 2 Impaired mobility 2 Mild sensory loss, numbness 2 Loss of bladder & bowel function 2 Neurological impairment 4 Pain and discomfort 2,3 Weakness in extremities 2 Interference with daily activities 3 Anemia, neutropenia & thrombocytopenia 4 Loss of appetite Beer TM, et al. N Engl J Med. 2014;371(5): Farrell C. Br J Nurs. 2013;22(10):S4-S Autio KA et al. J Oncol Pract. 2013;9(5): Selvaggi G et al. Crit Rev Oncol Hematol. 2005;56(3): Hamilton W et al. Br J Gen Pract. 2015;65(637):e

39 Median Progression To Symptomatic Disease on COU-302 (12 months) CLINICAL PROGRESSION Presence of symptoms associated with bone metastases Fatigue, generalized weakness 3 Interference with sleep 4 Dyspnea 3 Impaired mobility 3 Mild sensory loss, numbness 3 Loss of bladder & bowel function 3 Neurological impairment 5 Pain and discomfort 3,4 Weakness in extremities 3 Interference with daily activities 4 Anemia, neutropenia & thrombocytopenia 5 Loss of appetite Ryan CJ, et al. N Engl J Med. 2013;368(2): Ryan CJ, et al. Lancet Oncol. 2015;16(2): Farrell C. Br J Nurs. 2013;22(10):S4-S Autio KA et al. J Oncol Pract. 2013;9(5): Selvaggi G et al. Crit Rev Oncol Hematol. 2005;56(3): Hamilton W et al. Br J Gen Pract. 2015;65(637):e

40 How do we sequence our therapies? Immunotherapy Sipuleucel-T Hormonal strategies Abiraterone, enzalutamide, etc. Radiopharmaceuticals Radium 223 Chemotherapies Docetaxel, cabazitaxel, mitoxantrone, cisplatin/etoposide 40

41 CHAARTED Study of ADT +/- Docetaxel in mcspc: OS Sweeney CJ et al N Engl J Med Aug 20;373(8):737 41

42 STAMPEDE: PFS and OS for ADT + Docetaxel vs ADT HR 0.61; 95% CI ; p < HR 0.78; 95% CI ; p = HR 0.62; 95% CI ; p < HR 0.82; 95% CI ; p = James ND, et al. Lancet Mar 19;387(10024):

43 ALSYMPCA: Overall Survival Parker C, et al. N Engl J Med. 2013;369:

44 ALSYMPCA: Subgroup Analyses Parker C, et al. N Engl J Med. 2013;369:

45 Key Takeaways Diverse treatment portfolio for patients with mcrpc Aggressive use of non-hormonal therapies can be considered in conjunction with or following hormonal strategies We frequently use these therapies later than we should Variations in histology, driver biology, clinical phenotype and prognostic factors evolve with treatment Treatments have been shown to work in sequence Working hypothesis: Many of these mechanisms may be synergistic if used in combination 45

46 Bladder Cancer what s new? Anti-PD-1 and PDL-1 monotherapy improves clinical outcomes In post-platinum metastatic UC In platinum ineligible UC Front line studies in muc alone, in combination with platinum chemotherapy ongoing Adjuvant studies ongoing 46

47 Evolution of Metastatic Bladder Cancer Management Pembrolizumab FDA granted priority review designation in UC, platinum-ineligible and postplatinum February 6, 2017 No major improvement in therapeutic efficacy in the past >30 years Standard MVAC Cancer 1989 Docetaxel JCO 1997 Gem/Cis JCO 2000 amvac JCO 2001 Vinflunine EMA approved 2009 Nivolumab FDA accelerated approval: advanced UC, postplatinum February 2, 2017 Durvalumab FDA breakthrough therapy designation: PD-L1+ advanced UC, post-platinum Feb 17, 2016 Gemcitabine Eur J Cancer 1998 Paclitaxel JCO 2002 Atezolizumab FDA accelerated approval: advanced UC, post-platinum May 18, 2016 Atezolizumab FDA accelerated approval: advanced UC, platinum - ineligible April 18,

48 PD-1/PD-L1 inhibitors MPDL3280A/Atezolizumab (Genentech) Durvalumab (Astra Zeneca) Avelumab (Pfizer) Nivolumab (BMS) Pembrolizumab (Merck) 48

49 IMvigor210 Cohort 2: Study Design * *A hierarchical testing procedure was used to assess whether the ORR was significantly higher than the historical control ORR of 10% at an α level of Figure: Dreicer, R. Abs 355. ASCO

50 IMvigor210 Cohort 2: Baseline Characteristics 50 Dreicer, R. Abs 355. ASCO

51 IMvigor210 Cohort 2: Response Rates IC 0 IC 1 IC 1/2/3 2/3 All ORR: confirmed IRF RECIST v1.1 9% 11% 19% 28% 16% CR rate: confirmed IRF RECIST v1.1 2% 4% 9% 15% 7% Statistically significant improvement in ORR, compared to historical control ORR of 10% (p= for all patients; p< in IC2/3; p= in IC1/2/3) ORR and CR observed in all PD- L1 subgroups Increased responses in higher PD-L1 status subgroups Dreicer, R. Abs 355. ASCO

52 Atezolizumab Phase 2 in UC Median OS: 7.9 months (95% CI ) 310 patients Single arm study Analyzed PD-L1 status on TILs Primary endpoint: ORR Secondary endpoints: Duration of response, PFS, OS, safety 52 Rosenberg JE et al, Lancet, 2016, 387:

53 IMvigor210: Safety Summary Most AEs were Grade 1-2 Safety compares favorably with historical controls Dreicer, R. Abs 355. ASCO

54 IMvigor210 Cohort 1: Study Design Figure: Balar, A. Abs LBA4500. ASCO

55 IMvigor210 Cohort 1: Baseline Characteristics Balar, A. Abs LBA4500. ASCO

56 IMvigor210 Cohort 1: Response Rates IC 0 IC 1 IC 1/2/3 2/3 All ORR: confirmed IRF RECIST v1.1 21% 23% 25% 28% 24% CR rate: confirmed IRF RECIST v1.1 8% 6% 6% 6% 7% Median duration of follow-up 14.4 months (range, months) ORR and CR observed in all PD-L1 subgroups Increased responses in higher PD-L1 status subgroups Balar, A. Abs LBA4500. ASCO

57 IMvigor210 Atezolizumab Platinum ineligible Balar AJ et al, Lancet, 2017, 389:

58 Pembrolizumab Phase 3 in UC Keynote Metastatic Urothelial carcinoma Cisplatin refractory (including within 12 months after adj/neoadj therapy) <2 lines of previous treatment R* Pembrolizumab 200mg IV q3 weeks Chemotherapy (paclitaxel, docetaxel, vinflunine) Co-Primary Endpoints: Ø PFS & OS Secondary Endpoints: Ø ORR Ø Duration of confirmed response Ø Safety 58 Bellmunt J et al, NEJM, 2017, Epub

59 Pembrolizumab Phase 3 in UC Keynote 045 Randomized 542 patients Well-balanced between two arms 59 Bellmunt J et al, NEJM, 2017, Epub

60 Pembrolizumab Phase 3 in UC Keynote 045 Median 10.3 months Median 7.4 months Bellmunt J et al, NEJM, 2017, Epub

61 Pembrolizumab Phase 3 in UC Keynote 045 Response rates Pembrolizumab (n=266) Chemotherapy (n=255) Event Any grade Grade 3, 4, or 5 Any grade Grade 3, 4, or 5 Leading to discontinuation of treatment 5.6% 4.5% 11% 6.3% Leading to death 1.5% 1.5% 1.6% 1.6% Fatigue 13.9% 1.1% 27.8% 4.3% Nausea 10.9% 0.4% 24.3% 1.6% Diarrhea 9% 1.1% 12.9% 0.8% Anemia 3.4% 0.8% 24.7% 7.8% Neutropenia 0% 0% 15.3% 13.3% Alopecia 0% 0% 37.6% 0.8% Pruritus 19.5% 0% 2.7% 0.4% Pneumonitis 4.1% 2.3% 0.4% 0% Hypo/hyperthyroidism 10.2% 0% 1.6% 0% Adrenal insufficiency 0.4% 0.4% 0% 0% 61 Bellmunt J et al, NEJM, 2017, Epub

62 Nivolumab phase 2 in UC Checkmate 275 Primary endpoint: Overall response in all and in PD-L1 positive patients Secondary endpoints: PFS, OS 62 Sharma P et al, Lancet Oncol, 2017, Epub

63 Nivolumab phase 2 in UC Checkmate Sharma P et al, Lancet Oncol, 2017, Epub

64 Nivolumab phase 2 in UC Checkmate Sharma P et al, Lancet Oncol, 2017, Epub

65 Future development of PD1 inhibitors in UC BCGunresponsive Non-muscleinvasive bladder cancer Muscle-invasive bladder cancer Metastatic urothelial cancer 1 st line Low grade In development High grade Pembrolizumab + BCG Neoadjuvant Atezolizumab Pembro + Chemo Nivo + Urelumab Adjuvant Atezolizumab Ph III Nivolumab Ph III Cisplatin-eligible Durvalumab + Tremelimumab (Ph III) Cisplatin-ineligible Pembrolizumab 2 nd line and beyond Pembrolizumab Atezolizumab Trimodality Pembrolizumab + RT Schema modified from: Fakhrejahani F et al. Curr Opin Urol 2015 Maintenance Avelumab (Ph III) Pembrolizumab Platinum-refractory Pembrolizumab (Ph III vs chemo) Atezolizumab (Ph III vs chemo) Pembrolizumab + acalabrutinib (Ph II) Modified from Elizabeth Plimack, ASCO

66 Key Takeaways Metastatic Bladder cancer rapidly evolving landscape including PD-1 and PDL-1 inhibitors Combinations with chemo and other checkpoints under development As anti-pd-1/pdl-1 strategies get moved up look for novel salvage strategies Long term survivors in metastatic bladder cancer! 66