Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Advances in Cancer Therapeutics: A Survey of 'What's New in Oncology'

32 views

Published on

Advances in Cancer Therapeutics: A Survey of 'What's New in Oncology'
Marcus C. Ravnan, PharmD, FCSHP, FASHP

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

Advances in Cancer Therapeutics: A Survey of 'What's New in Oncology'

  1. 1. Advances in Cancer Therapeutics: A Survey of 'What's New in Oncology'
  2. 2. Disclosure of Interest In preparing this presentation, I disclose that there are no potentially biasing relationships of a professional or personal nature that exist related to the content or direction of this educational presentation. I have no relevant financial interests or other relationships with the manufacturer(s) of commercial products and/or provider(s) of commercial services discussed in this educational presentation.
  3. 3. Statement of Need This presentation is designed to meet the needs of pharmacists who practice in various settings where they may encounter patients with cancer. In order to update participants on a few key issues, the presentation specifically targets areas where the therapeutic landscape has and is rapidly changing.
  4. 4. On completing of this activity participants will be able to: On completion of this activity the attendee will;  have a working knowledge of contemporary management strategies that incorporate recently approved cancer and immune targeting agents.  be able to describe major uses, indications, mechanism or mechanisms of action and side effects of each agent discussed.  be able to assess the efficacy of selected agents in specific disease statesthat are reviewed.  be able to develop a plan to monitor and manage the side effects of each agent discussed.  be able to provide patient education and counseling for selected agents and disease statemanagement.  and will be able to apply evidence-based treatment plans in oncology to patient case examples.
  5. 5. Breast Cancer - 2.8 million breast cancer survivors strong • In 2019, almost 300,000 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 65,000 new cases of non- invasive (in situ) breast cancer. – About 2,700 new cases of invasive breast cancer are expected to be diagnosed in men in 2010. A man’s lifetime risk of breast cancer is about 1 in 1,000. • About 42,000 women in the U.S. are expected to die in 2019 from breast cancer, though death rates have been decreasing since 1990s. • Invasive disease therapy usually consists of surgery/radiation followed by systemic adjuvant therapy + hormonal therapy • Metastatic disease is found in 20% as recurrence and in 6-10% at initial presentation • 20% of breast cancers have amplification/over-expression of human epidermal growth factor receptor-2 (HER-2) www.cancer.org Breast Cancer Facts and Figures 2013-2014 Arch Pathol LabMed. 2007;131:18-43 www.nccn.orgNCCN Guideline. Breast Cancerversion 1.2018
  6. 6. Breast Cancer • Endocrine or hormone responsive • Less aggressive, more chemotherapy sensitive, metastatic spread late, typically to bone, recurrence + 20 years • HER-2 positive • Aggressive, varying degree of chemo-resistance, early visceral and CNS metastatic spread • Triple negative • Aggressive, optimal therapy still remains undefined Arch Pathol Lab Med. 2007;131:18-43 Oncologist. 2009;14:320-368 www.nccn.org NCCN Guideline. Breast Cancer version 1.2018
  7. 7. Early Stages • Need to measure risk to determine if appropriate for surveillance and more frequent checks • Lumpectomy ± Radiation or total mastectomy + reconstruction – Endocrine Therapy (biopsy guided) – Risk reduction measures – Increased follow up intervals www.nccn.org NCCN Guideline. Breast Cancer version 1.2018
  8. 8. Later Stages • Surgery ± Radiation ± Therapy • Therapy depends on ER/PR and HER-2 status • ER/PR(+) and HER-2(+): adjuvant endocrine therapy ± adjuvant chemotherapy with trastuzumab ± pertuzumab • ER/PR(+) and HER-2(-): adjuvant endocrine therapy ± adjuvant chemotherapy • ER/PR(-) and HER-2(+): adjuvant chemotherapy with trastuzumab ± pertuzumab • ER/PR(-) and HER-2(-): adjuvant chemotherapy • Metastatic: Palliative chemotherapy; Trastuzumab±Pertuzumab or Ado-Trastuzumab; CDK4/6 inhibitors; mTOR inhibitor; PARP inhibitors, Immune
  9. 9. HER-2 • Transmembrane tyrosine kinase • Extracellular domain serves as a binding site • Must “pair” hetero-dimer or homo-dimer to initiate a downstream signal • HER-2 : HER-3 elicits the most potent signal • Proliferation, Angiogenesis, anti-Apoptosis, enhanced receptor sensitivity New Engl J Med. 2007;357:39-51 Cancer Treat Rev. 2009;35:121-136 J Clin Oncol. 2009;27:5838-5847
  10. 10. HER-2 Over-Expressing Breast Cancer cell division HER-2 nucleus cancer cell Trastuzumab Anti-HER-2 Antibody HER-2 Oncogene: amplified/overexpressed in 20-25% of cases Lapatinib Dual HER-1/HER-2 Tyrosine Kinase Inhibitor Pertuzumab Anti-HER-2 Antibody T-DM1 Antibody-Drug Conjugate
  11. 11. HER-2 Signal Pathways Nuclear Growth Signal
  12. 12. HER-2 Ribbon Diagram
  13. 13. Domain Selective Dual Inhibition
  14. 14. Cleopatra Study Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer Sandra M. Swain, M.D., José Baselga, M.D., Sung-Bae Kim, M.D., Jungsil Ro, M.D., Vladimir Semiglazov, M.D., et al., for the CLEOPATRA Study Group February 19, 2015 N Engl J Med 2015; 372:724-734
  15. 15. 42% vs. 25% @2years ESMO 2014 Congress. Abstract 350O. Presented September 28, 2014 ~11,832 alive PF at 2 years
  16. 16. Pertuzumab Overall Survival Impact 15% difference Combination provided 15.7 months Overall survival
  17. 17. Adverse Events Baselga J et al. N Engl J Med 2012;366:109-119
  18. 18. Pertuzumab – Perjeta • Indications: Adjuvant, Neo-adjuvant Progressive/MBC • Dose & Administration: Initially 840mg in 250ml’s NS IV over 60 minutes followed by 420mg every 3 weeks over 30-60 minutes (3-6 cycles pre-operatively in neoadjuvant setting) with 8mg/kg then 6mg/kg trastuzumab which will continue to complete a full year of trastuzumab therapy or until disease progression in MBC
  19. 19. Pertuzumab • Side Effect Profile: Not significantly different vs. monotherapy, Infusion reactions, diarrhea, fatigue, alopecia, neutropenia, rash, fever/chills – higher incidence of diarrhea, rash and dry skin • Warnings & Precautions: Cardiomyopathy, Embryo-Fetal toxicity, Antibody development • Pre-medications: Antihistamine, Dexamethasone*, APAP • Monitoring: Baseline LVEF, repeat every 3-6 months
  20. 20. JP is a 67 year old female recently evaluated after mammography revealed changes in contra-lateral tissue at 3-o’clock position. Surgical biopsy sample ER+/PR-, HER-2 amplification (fish). Staged T1N2M1 PMH: BCA at 52 tx radiation, surgical excision, adjuvant chemotherapy, 10 years of tamoxifen.
  21. 21. Ado-trastuzumab emtansine – Kadcyla + Pertuzumab Antibody Trastuzumab Tubulin polymerization inhibitor DM-1 Linker Machinery Blockade and Cell Death Clin Cancer Res January 15, 2014 20:278-280 JCO May 10, 2014 vol. 32 no. 14. 1437-1444
  22. 22. Trastuzumab Emtansine with or without Pertuzumab versus Trastuzumab plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study Journal of Clinical Oncology 2017 35141-148.
  23. 23. Published in: Edith A. Perez; Carlos Barrios; Wolfgang Eiermann; Masakazu Toi; Young-Hyuck Im; Pierfranco Conte; Miguel Martin; Tadeusz Pienkowski; Xavier Pivot; Howard A. Burris; Jennifer A. Petersen; Sven Stanzel; Alexander Strasak; Monika Patre; Paul Ellis; Journal of Clinical Oncology 2017 35141-148.
  24. 24. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomized open-label phase 3 trial The Lancet Oncology. VOLUME 18, ISSUE 6, P743-754, JUNE 01, 2017
  25. 25. Advanced Disease
  26. 26. Baseline Population Characteristics
  27. 27. Overall Survival Analysis
  28. 28. Overview of AEs
  29. 29. Grade 3+ AEs TPC vs. T-DM1
  30. 30. Improved Overall Survival
  31. 31. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer Gunter von Minckwitz, M.D., Chiun-Sheng Huang, M.D., Ph.D., Max S. Mano, M.D., Ph.D., Sibylle Loibl, M.D., Eleftherios P. Mamounas, M.D., Michael Untch, M.D., Ph.D., Norman Wolmark, M.D., Priya Rastogi, M.D., Andreas Schneeweiss, M.D., Andres Redondo, M.D., Ph.D., Hans H. Fischer, M.D., William Jacot, M.D., Ph.D., et al. The KATHERINE Investigators February 14, 2019 N Engl J Med 2019; 380:617-628
  32. 32. KATHERINE Results
  33. 33. T-DM1 overall
  34. 34. KATHERINE Results Side Effect Profile Common Side Effect Profile Neutropenia Fatigue Altered ejection fraction Thrombocytopenia Sensory neuropathy Myalgia Headache
  35. 35. CONCLUSIONS Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. KATHERINE ClinicalTrials.gov
  36. 36. • You have blood relatives (grandmothers, mother, sisters, aunts) on either your mother's or father's side of the family who had breast cancer or ovarian diagnosed before age 50. • There is both breast and ovarian cancer on the same side of the family or in a single individual. • You have a relative(s) with triple-negative breast cancer. • Women in your family have had cancer in both breasts. • You are of Ashkenazi Jewish (Eastern European) heritage. • You are African American and have been diagnosed with breast cancer at age 35 or younger. • A man in your family has had breast cancer. • There is a known abnormal breast cancer gene in your family where breast and ovarian cancer family history is positive Risk of BRCA1 or BRCA2 mutations
  37. 37. Targeted Therapies - PARP inhibitors Prz Menopauzalny. 2016 Dec; 15(4): 215–219. Published online 2017 Feb 8. doi: 10.5114/pm.2016.65667
  38. 38. Inhibiting PARP-1 as it relates to Single-Strand Breaks Increases Double-Strand DNA Damage PARP Inhibition of PARP-1 prevents -recruitment of DNA repair enzymes -leads to failure of SSB repair -accumulation of SSBs XRCC1 LigIII PNK 1 pol β During S-phase, replication fork is arrested at site of SSB DNA single strand break (SSB) damage Degeneration into Double strand breaks Poly (ADP-ribose) Polymerase Gynecol Oncol. 2015 Feb 25. pii: S0090-8258(15)00657-5. doi:
  39. 39. DNA Repair Inhibitors in Cancer Cells: 2 Modes of Action • Potentiation – Inhibition of DNA repair following DNA-damaging agents – Original hypothesis • Synthetic lethality – Selected cancer cells lose DNA repair pathways, whereas normal cells remain unaffected – Targeting these defective cells may cause selective cell kill with an increased therapeutic ratio – May allow for a novel targeted approach to cancer treatment Bentle MS et al J Mol Histol. 2016 Sep;37(5-7):203-18 Donal P. McLornan, M.B., B.Ch., Ph.D., Alan List, M.D., and Ghulam J. Mufti, D.M. N Engl J Med 2014; 371:1725-1735October 30, 2014DOI: 10.1056/NEJMra1407390
  40. 40. • Depends on genetic mutations – BRCA1/ BRCA2 mutations • These mutations lead to difficulty in repairing DNA damage • PARP inhibitors enhance that difficulty • Can be a germline (inherited) mutation OR a somatic (tumor only) mutation • 5-10% of breast cancer patients have BRCA1/BRCA2 mutations Why do they work better in some tumors?
  41. 41. FDA Approved PARP inhibitors • Olaparib – Lynparza • Talazoparib - Talzenna • Rucaparib – Rubraca • Niraparib - Zejula
  42. 42. • Talazoparib (TALA) is a highly potent dual-mechanism PARP inhibitor1-3 – Inhibits the PARP enzyme – Traps PARP on single-stranded DNA breaks4 – Prevents repair of DNA damage, resulting in cell death • Phase 1 trial established a tolerable dose of 1 mg/day for continuous dosing (fed or fasting)5 • Single-agent activity in other tumor types (prostate, ovarian, SCLC) • The phase 2 ABRAZO trial showed encouraging efficacy and safety in patients with germline BRCA1/2 mutations and prior platinum therapy or at least 3 prior cytotoxic regimens6 Figureadapted from MuraiJ et al. Cancer Res. 2012;72:5588-5599, with permission fromAACR. 1. Ashworth A. J Clin Oncol. 2008;26:3785-3790. 2. Jalve M, Curtin NJ. Ther Adv Med Oncol. 20113:257-267. 3. Helleday T. Mol Oncol. 2011;5:387-393. 4. Lord CJ, Ashworth A. Science. 2017;355:1152-1158. 5. de Bono J et al. Cancer Discov. 2017;7:620-629. 6. Turner NC et al. Presented at ASCO; June 3, 2017; Chicago,IL. Abstract 1007. ABRAZO Pha se 1 (n = 14)a Prior Platinum (n = 48) ≥ 3 Lines, No Platinum (n = 35) Confirmed ORR, % (95% CI) 50% 21% (10, 35) 37% (22, 55) PFS, mo (95% CI) 7.5 4.0 (2.8, 5.4) 5.6 (5.5, 7.8) CBR24, % (95% CI) 86% 38% (24, 53) 66% (48, 81)
  43. 43. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation August 23, 2018 N Engl J Med 2018; 379:753-763 Jennifer K. Litton, M.D., Hope S. Rugo, M.D., Johannes Ettl, M.D., Sara A. Hurvitz, M.D., Anthony Gonçalves, M.D., Ph.D., Kyung-Hun Lee, M.D., Ph.D., Louis Fehrenbacher, M.D., Rinat Yerushalmi, M.D., Lida A. Mina, M.D., Miguel Martin, M.D., Ph.D., Henri Roché, M.D., Ph.D., Young-Hyuck Im, M.D., Ph.D., et al.
  44. 44. Baseline Characteristics
  45. 45. Results
  46. 46. Results
  47. 47. Talazoparib in Breast Cancer Conclusions • EMBRACA is the largest randomized trial evaluating a PARP inhibitor in patients with advanced breast cancer and a germline BRCA1/2 mutation • Talazoparib resulted in prolonged progression-free survival vs physician’s choice of therapy by blinded central review – HR: 0.54 (95% CI, 0.41, 0.71); P < .0001 • All key secondary efficacy endpoints demonstrated benefit with talazoparib – Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months). – Global Health Status/Quality of Life showed overall improvement from baseline and a delay in the time to clinically meaningful deterioration in patients receiving talazoparib – HR: 0.38 (95% CI, 0.26, 0.55); P < .0001 • Talazoparib was generally well tolerated, with few adverse events resulting in treatment discontinuation
  48. 48. TALA (n = 286) Overall PCT (n = 126) All Grade Grade 3 Grade 4 All Grade Grade 3 Grade 4 No. of patients with ≥ 1 AE, no. (%) 194 (67.8%) 140 (49.0%) 17 (5.9%) 63 (50.0%) 29 (23.0%) 19 (15.1%) Anemia 151 (52.8%) 110 (38.5%) 2 (0.7%) 23 (18.3%) 5 (4.0%) 1 (0.8%) Neutropenia 99 (34.6%) 51 (17.8%) 9 (3.1%) 54 (42.9%) 25 (19.8%) 19 (15.1%) Thrombocytopenia 77 (26.9%) 32 (11.2%) 10 (3.5%) 9 (7.1%) 2 (1.6%) 0 Lymphopenia 21 (7.3%) 9 (3.1%) 0 4 (3.2%) 0 1 (0.8%) Febrile neutropenia 1 (0.3%) 0 1 (0.3%) 1 (0.8%) 0 1 (0.8%)
  49. 49. Active Agents in Ovarian Cancer Select FDA approved Altretamine Carboplatin Cisplatin Gemcitabine/ Carboplatin Paclitaxel Pegylated liposomal doxorubicin Topotecan Not FDA approved Chlorambucil Cyclophosphamide Docetaxel Doxorubicin Epirubicin Etoposide 5-FU/LV Gemcitabine Ifosfamide Irinotecan Melphalan Methotrexate Thiotepa Vinorelbine Agents Added or Considered Aromatase inhibitors Bevacizumab Pemetrexed Tamoxifen
  50. 50. The Role of Paclitaxel in First-line Therapy for Ovarian Carcinoma Study # Pts Regimen Median PFS (mo) Median OS (mo) GOG 1321 377 III suboptimal-IV Cisplatin/ Paclitaxel (24 h) x 6 14.1 26.3 Cisplatin 100 mg/m2 x 6 16.4 30.2 Paclitaxel 200 mg/m2 (24 h)* 10.8 25.9 ICON 32 2074 I-IV Carboplatin/ Paclitaxel (3 h) 17.3 36.1 Carboplatin or CAP 16.1 35.4 CAP = cyclophosphamide, doxorubicin, cisplatin GOG = Gynecologic Oncology Group ICON = International Collaborative Ovarian Neoplasm Group OS = overall survival PFS = progression-free survival 1. Muggia FM, et al. J Clin Oncol. 2000;18(1):106-115. 2. International Collaborative Ovarian Neoplasm Group. Lancet. 2002;360(9332):505-515. *CR/PR rates on paclitaxel monotherapy (42%) vs cisplatin regimens (67%), P <.001 NCCN Version 2.2018; March 2018
  51. 51. The Schedule of Paclitaxel in First-line Therapy for Ovarian Carcinoma Study # Pts Regimen Median PFS (mo) Median OS (mo) GOG 1581 792 III optimal Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) 19.4 48.8 Carboplatin AUC 7.5 Paclitaxel 175 mg/m2 (3 h) * 20.7 56.7 * RR progression 0.88 (95% CI) and RR death 0.86 (95% CI) HR =0.86 (99% CI) AGO2 798 IIB-IV Cisplatin 75 mg/m2 Paclitaxel 185 mg/m2 (24 h) 19.1 44.1 Carboplatin AUC 6 Paclitaxel 185 mg/m2 (3 h) 17.2 43.3 HR = 1.050 (95% CI) HR =1.045 (95% CI) More toxicity with the cisplatin regimens 1. Bookman MA, et al. Int J Gynecol Cancer. 2003;13(s2):149–155. 2. du Bois AD, et al. J Natl Cancer Inst. 2003;95(17):1320-1329. AGO = Arbeitsgemeinschaft Gynaekologische Onkologie CI = confidence interval GOG = Gynecologic Oncology Group HR = hazard ratio; OS = overall survival PFS = progression-free survival RR = relative risk
  52. 52. Olaparib in BRCA Linked Cancer
  53. 53. Study 19: Progression-free survival 0 Time from randomization (months) 136 104 51 23 6 0 0 129 72 23 7 1 0 0 At risk (n) Olaparib Placebo 0.6 0.8 0.9 0 0.1 0.2 0.3 0.4 0.5 0.7 1.0 3 6 9 12 15 18 No. of events: Total patients (%) Median PFS (months) Olaparib 60:136 (44.1) 8.4 Placebo 93:129 (72.1) 4.8 Hazard ratio 0.35 (95% CI, 0.25–0.49) P<0.00001 Olaparib 400 mg bid Placebo Randomized treatment Proportionofpatients progressionfree Ledermann et al. J Clin Oncol 2011;29 (suppl; abstr 5003); N Engl J Med. 2012 Apr 12;366(15):1382-92.
  54. 54. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomized, double-blind, placebo-controlled, phase 3 trial Robert L Coleman, Amit M Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, et al. The ARIEL3 Investigators VOLUME 390, ISSUE 10106, P1949-1961, OCTOBER 28, 2017
  55. 55. PARP-I in Advanced Ovarian
  56. 56. • Nausea • Fatigue • Anemia • Vomiting • Diarrhea • Neutropenia • Myelodysplatic syndrome (MDS) and/or acute myeloid leukemia (AML) occurred in 2% of the patients Olararib Most common side effects
  57. 57. –Nausea –Fatigue (muscular weakness) –Vomiting –Anemia –Abdominal pain –Changes in taste –Myelodysplatic syndrome (MDS) and/or acute myeloid leukemia (AML) occurred in 2% of the patients Rucaparib Most common side effects
  58. 58. – Nausea – Thrombocytopenia – Fatigue – Anemia – Vomiting – Neutropenia – Myelodysplatic syndrome (MDS) and/or acute myeloid leukemia (AML) occurred in 2% of the patients Niraparib Most common side effects
  59. 59. Drug Maintenance Treatment Treatment Schedule Starting dose Lynparza (Olaparib) Yes Yes Ovarian Yes Breast Twice daily 2 tablets twice a day OR 8 capsules twice a day Rubraca (Rucaparib) No Yes Ovarian Twice daily 2 tablets twice a day Zejula (Niraparib) Yes Ovarian No Once daily 3 capsules once a day Talzenna (Talazoparib) No Yes Breast Once daily 1mg capsule once a day Summary of the PARP Inhibitors – Teaching Tool
  60. 60. Immune Therapy 2018 Nobel Prize Winner Tasuku Honjo James P. Allison
  61. 61. A Completely New Direction Wolchok, et al. N Engl J Med 2013; 369:122-133 Hamid N Engl J Med 2013; 369:134-144
  62. 62. Pembrolizumab/Nivolumab Lymph Tissue Tumor Site J of Immunology October 15, 2014 vol. 193 no. 8 3835-3841 Nature 515: 496–498 doi:10.1038/515496a
  63. 63. Teaching Tool
  64. 64. Efficacy of PD-1s in Metastatic Melanoma Topalian SL, Hodi FS, Brahmer JR, et al. N Engl J Med. 2012;366:2443-54. Hamid O, Robert C, Ribas A, et al. J Clin Oncol. 2014;32(suppl 5S):abstr 3000. Ribas A, Hodi FS, Kefford R, et al. J Clin Oncol. 2014;32(suppl 5S):abstr LBA9000.
  65. 65. Pembrolizumab - Keytruda • Indications: Metastatic Melanoma following progressionafter ipilimumab and or BRAF inhibition therapy, • Dose & Administration: Initially 2mg/kg IV over 30 minutes every 3 weeks. Although not approved, doses of 10mg/kg have been used in clinical studies. • Side Effect Profile: Grade 1 immune related, initiate corticosteroid therapy and defer therapy. Grade 3 or 4 – Prednisone 40mg daily or equivalent for 7 days followed by slow taper with therapy withdrawal. Thyroid replacement is needed in a subset of patients • Warnings & Precautions: Immune related side effects appear to have an onset of around 2-5 months in most patients • Pre-medications: Antihistamine, APAP • Monitoring: TFTs, LFTs, Hepatitis & TB, CXR, BUN/SCR http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
  66. 66. Nivolumab - Opdivo • Indications: Metastatic Melanoma following progressionafter ipilimumab and or BRAF inhibition therapy • Dose & Administration: Initially 3mg/kg IV over 60 minutes every 2 weeks. • Side Effect Profile: Grade 1 immune related, initiate corticosteroid therapy and defer therapy. Grade 3 or 4 – Prednisone 40mg daily or equivalent for 7 days followed by slow taper with therapy withdrawal. Thyroid replacement is needed in a subset of patients • Warnings & Precautions: Immune related side effects appear to have an onset of around 1-5 months in most patients • Pre-medications: Antihistamine, APAP • Monitoring: TFTs, LFTs, Hepatitis & TB, CXR, BUN/SCR http://packageinserts.bms.com/pi/pi_opdivo.pdf
  67. 67. Pembrolizumab Indications • Melanoma: 200 mg every 3 weeks. • NSCLC: 200 mg every 3 weeks. • HNSCC: 200 mg every 3 weeks. • cHL or PMBCL: 200 mg every 3 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. • Urothelial Carcinoma: 200 mg every 3 weeks. • MSI-H Cancer: 200 mg every 3 weeks for adults and 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. • Gastric Cancer: 200 mg every 3 weeks. • Cervical Cancer: 200 mg every 3 weeks. • HCC: 200 mg every 3 weeks. • MCC: 200 mg every 3 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics.
  68. 68. Nivolumab Indications • Adjuvant treatment of melanoma 240 mg every 2 weeks or 480 mg every 4 weeks. • Metastatic non-small cell lung cancer 240 mg every 2 weeks or 480 mg every 4 weeks. • Small cell lung cancer 240 mg every 2 weeks. • Advanced renal cell carcinoma 240 mg every 2 weeks or 480 mg every 4 weeks. • OPDIVO 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks. • • Classical Hodgkin lymphoma 240 mg every 2 weeks or 480 mg every 4 weeks. • Recurrent or metastatic squamous cell carcinoma of the head and neck 240 mg every 2 weeks or 480 mg every 4 weeks. • Locally advanced or metastatic urothelial carcinoma 240 mg every 2 weeks or 480 mg every 4 weeks. • Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer 240 mg every 2 weeks or 3 mg/kg followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then 240 mg every 2 weeks. • Hepatocellular carcinoma 240 mg every 2 weeks or 480 mg every 4 weeks.
  69. 69. Atezolizumab – (Tecentriq) Indications – PD-L1 • Urothelial Carcinoma: 1200 mg intravenously (IV) over 60 minutes every 3 weeks. • Non-Small Cell Lung Cancer (NSCLC): 1200 mg IV over 60 minutes, followed by bevacizumab, paclitaxel and carboplatin, on the same day, every 3 weeks for a maximum of 4-6 cycles. Following completion of chemotherapy, 1200 mg IV followed by bevacizumab, every 3 weeks.
  70. 70. Durvalumab - Imfinzi Indications – PD-L1 • Urothelial Carcinoma: 10mg/kg intravenously (IV) over 60 minutes every 2 weeks. • Non-Small Cell Lung Cancer (NSCLC): 10mg/kg intravenously (IV) over 60 minutes every 2 weeks.
  71. 71. Teaching Tool
  72. 72. The Oncologist. 2016;21:1-10. Immunotherapeutics
  73. 73. The Race to the Cure Winning may be Closer than we Think

×