Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories
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The document outlines various Phase 3 clinical trials and practice aids focusing on immuno-oncology treatments for bladder and renal cell cancers, detailing recruitment statuses for each trial as of January 2017. It also highlights general guidelines for managing immune-mediated adverse reactions associated with immune checkpoint inhibitors, emphasizing early recognition and treatment strategies. Additionally, it provides insights into selected clinical trials involving checkpoint inhibitors in prostate cancer, reflecting ongoing research in this domain.
Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories
- 1. Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerview.com/XZX40. Selected Immuno-Oncology Phase 3 Trials in Bladder Cancer and Renal Cell Carcinoma1,a PRACTICE AID This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients. Bladder Cancer • N = 800 • NCT02450331 IMvigor010 Recruiting Atezolizumab Observationvs Adjuvant First Line • N = 640 • NCT02632409 CheckMate 274 Nivolumab Placebovs • N = 739 • NCT03244384 AMBASSADOR Pembrolizumab Observationvs Maintenance • N = 668 • NCT02603432 JAVELIN Bladder 100 Avelumab maintenance • N = 1,200 • NCT02516241 DANUBE Durvalumab +/- tremelimumab Chemotherapyvs • N = 1,200 • NCT02807636 IMvigor130 • N = 990 • NCT02853305 KEYNOTE-361 Atezolizumab +/- platinum-based chemotherapy Pembrolizumab +/- platinum-based chemotherapy Chemotherapyvs • N = 897 • NCT03036098 CheckMate 901 Nivolumab + ipilimumab Chemotherapyvs • N = 650b • NCT03361865 KEYNOTE-672/ECHO-307 Nivolumab + chemotherapy Pembrolizumab + epacadostat Placebovs • N = 648 • NCT03374488 KEYNOTE-698/ECHO-303 Pembrolizumab + epacadostat Pembrolizumab + placebo vs Second Line Recruiting Recruiting Recruiting Recruiting Recruiting Recruiting Recruiting Not yet recruiting Not yet recruiting Chemotherapyvs
- 2. Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerview.com/XZX40. Selected Immuno-Oncology Phase 3 Trials in Bladder Cancer and Renal Cell Carcinoma1,a PRACTICE AID a Recruitment status of each trial as of January 12, 2017. b In cisplatin-ineligible patients. 1. https://clinicaltrials.gov. Accessed January 22, 2017. Renal Cell Carcinoma • N = 766 • NCT03055013 PROSPER Recruiting Nivolumab Neoadjuvant and Adjuvant First Line • N = 800 • NCT03138512 CheckMate 914 Nivolumab + ipilimumab Placebovs Adjuvant • N = 950 • NCT03142334 KEYNOTE-564 Pembrolizumab • N = 830 • NCT02684006 JAVELIN Renal 101 Avelumab + axitinib Sunitinibvs • N = 840 • NCT02853331 KEYNOTE-426 Pembrolizumab + axitinib Sunitinibvs • N = 1,014 • NCT03141177 CheckMate 9ER Nivolumab + cabozantinib +/- ipilimumab vs • N = 630 • NCT03260894 KEYNOTE-679/ECHO-302 Pembrolizumab + epacadostat Standard of care vs • N = 664 • NCT03024996 IMmotion010 Atezolizumab • N = 1,750 • NCT03288532 RAMPART Durvalumab +/- tremelimumab • N = 735 • NCT02811861 CLEAR Lenvatinib + everolimus Sunitinibvs Lenvatinib + pembrolizumab Sunitinib Recruiting Recruiting Recruiting Not yet recruiting Recruiting Recruiting Recruiting Recruiting Recruiting Placebovs Placebovs
- 3. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients. Immuno-Oncology in the Clinic: General Guidelines for Recognizing and Managing Immune-Mediated Adverse Reactions1-4 PRACTICE AID Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerviewpress.com/XZX40. Checkpoint Inhibitors How Do They Work? Pseudoprogression6 Responses Fewer patients benefit, but for a longer duration Survival,% Time5 n Immune checkpoint therapy n Chemotherapy n Genomically targeted therapy Lymphoid Tissue Anti–CTLA-4 antibodies Cytotoxic T cell Dendritic cell CD28 B7 B7 CTLA-4 Tumor Microenvironment Anti–PD-L1 antibodies Anti–PD-1 antibodies PD-L1 Tumor PD-1 Start of treatment Time TumorSize Pseudoprogression Tumor cell T cell Blocking negative regulatory signals activates the immune system
- 4. Immuno-Oncology in the Clinic: General Guidelines for Recognizing and Managing Immune-Mediated Adverse Reactions1-4 PRACTICE AID Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerviewpress.com/XZX40. Immune-Mediated Adverse Reactions (IMARs) Immune checkpoint inhibitors are associated with important clinical benefits, but can also lead to a unique spectrum of IMARs Any organ system can be affected at any time throughout the treatment course • Fatigue • Dermatologic (rash, pruritus, blisters, vitiligo, ulcers) • Gastrointestinal (diarrhea, enterocolitis, transaminitis, hepatitis, pancreatitis) • Endocrine (thyroiditis, hypophysitis, adrenal insufficiency) • Pulmonary (pneumonitis) More common • Hematologic, cardiovascular, ocular, renal, neurologic Less common General Guidance for the Diagnosis and Treatment of IMARs Keys to Success IMARs often diagnosed by exclusion; other causes should be ruled out, including AEs of other therapies used, but immunotherapy-related toxicity should always be included in the differential If appropriate, immunosuppressive treatment is used, and patients generally recover from IMARs Early recognition, evaluation, and treatment of IMARs plus patient education are essential for best outcomes Management may require: • Corticosteroid or other immunosuppressive treatment • Interruption or discontinuation of therapy Use of immunosuppressive therapy to manage IMARs does not impact response to immunotherapy
- 5. Immuno-Oncology in the Clinic: General Guidelines for Recognizing and Managing Immune-Mediated Adverse Reactions1-4 1. http://www.uptodate.com/contents/toxicities-associated-with-checkpoint- inhibitor-immunotherapy. Accessed January 12, 2018. 2. Weber JS et al. J Clin Oncol. 2015;33:2092-2099. 3. Weber JS et al. Oncologist. 2016;21:1230-1240. 4. Puzanov I et al. J Immunother Cancer. 2017;5:95. 5. Sharma P, Allison JP. Cell. 2015;161:205-214. 6. West HJ. JAMA Oncol. 2015;1:115. PRACTICE AID Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerviewpress.com/XZX40. Withhold immunotherapy Corticosteroids if symptoms do not resolve in 1 wk (prednisone 0.5-1 mg/kg/d or equivalent) Taper corticosteroids over ≥1 mo to reduce recurrence Re-dose if toxicity resolves to grade ≤1 Continue immunotherapy (or consider temporary delay) Symptomatic therapy Discontinue immunotherapy Hospitalization & multidisciplinary evaluation High-dose corticosteroids (prednisone 1-2 mg/kg/d or equivalent) Taper high-dose corticosteroids over ≥1 mo until toxicity resolves to grade ≤1 Grade 2 (Mild-to-moderate symptoms) Grade 3/4 (Severe or life-threatening symptoms) Grade 1 (Minimal or no symptoms; diagnostic changes only) General Management Principles for IMARs If >4 weeks of immunosuppressants needed, administer antimicrobial/antifungal prophylaxis to prevent opportunistic infections If no improvement or progression, additional immunosuppressant treatment may be needed
- 6. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients. Selected Checkpoint Inhibitor Clinical Trials in Prostate Cancer1,a PRACTICE AID Access the activity,“Strengthening Our Grip on Immuno-Oncology in Genitourinary Cancers: Understanding Science Through Stories,”at www.peerviewpress.com/XZX40. a Recruitment status of each trial as of January 19, 2017. 1. https://clinicaltrials.gov. Accessed January 22, 2017. Prostate Cancer Neoadjuvant • N = 75 • Phase 2 NCT02506114 PROSTVAC-VF +/- ipilimumab Ipilimumabvs Recruiting mCRPC (Cont’d) mCRPC • N = 730 • Phase 3 IMbassador250 (NCT03016312) Atezolizumab + enzalutamide Enzalutamide Recruiting vs • N = 54 • Phase 2 NCT01804465 Sipuleucel-T + ipilimumab Recruiting • N = 58 • Phase 2 NCT02312557 Recruiting • N = 15 (AR-V7 expressing) • Phase 2 STARVE-PC (NCT02601014) Recruiting • N = 370 • Phase 2 KEYNOTE-199 (NCT02787005) Recruiting Pembrolizumab + enzalutamide Nivolumab + ipilimumab Pembrolizumab +/- enzalutamide • N = 74 • Phase 2 NCT02788773 Recruiting • N = 90 • Phase 2 CheckMate-650 (NCT02985957) Recruiting • N = 45 • Phase 2 NCT03093428 Radium-223 +/- pembrolizumab Recruiting • N = 27 • Phase 2 NCT03204812 Recruiting • N = 296 • Phase 1b, 2 JAVELIN PARP MEDLEY (NCT03330405) Recruiting • N = 180 • Phase 1 KEYNOTE-365 (NCT02861573) Recruiting Tremelimumab + durvalumab Avelumab + talazoparib Durvalumab +/- tremelimumab • N = 421 • Phase 1/2 NCT02484404 Recruiting Durvalumab + olaparib Nivolumab + ipilimumab Pembrolizumab + olaparib Pembrolizumab + enzalutamide Pembrolizumab + docetaxel • N = 300 • Phase 2 CheckMate 9KD (NCT03338790) Not yet recruiting Nivolumab + rucaparib Nivolumab + docetaxel Nivolumab + enzalutamide