AEs With ICI/Targeted Tx

CE / CME

Expert Strategies for Managing Adverse Events With Combination Immune Checkpoint Inhibitor/Targeted Therapy

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: May 25, 2023

Expiration: May 24, 2024

Eric Jonasch
Eric Jonasch, MD
Kathleen N. Moore
Kathleen N. Moore, MD, MS, FASCO

Activity

Progress
1
Course Completed

References

  1. Vaddepally RK, Kharel P, Pandey R, et al. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel). 2020;12:738.
  2. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139-148.
  3. Albarrán-Artahona V, Laguna J-C, Gorría T, et al. Immune-related uncommon adverse events in patients with cancer treated with immunotherapy. Diagnostics (Basel). 2022;12:2091.
  4. Winer A, Bodor JN, Borghaei H. Identifying and managing the adverse effects of immune checkpoint blockade. J Thorac Dis. 2018;10(suppl 3):S480-S489.
  5. Steven NM, Fisher BA. Management of rheumatic complications of immune checkpoint inhibitor therapy—an oncological perspective. Rheumatology (Oxford). 2019;58(suppl 7):vii29-vii39.
  6. Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16:563-580.
  7. Madden KM, Hoffner B. Ipilimumab-based therapy: consensus statement from the faculty of the melanoma nursing initiative on managing adverse events with ipilimumab monotherapy and combination therapy with nivolumab. Clin J Oncol Nurs. 2017;21(suppl 4):30-41.
  8. Weber JS, Postow M, Lao CD, et al. Management of adverse events following treatment with anti-programmed death-1 agents. Oncologist. 2016;21:1230-1240.
  9. Thompson LL, Pan CS, Chang MS, et al. Impact of ethnicity on the diagnosis and management of cutaneous toxicities from immune checkpoint inhibitors. J Am Acad Dermatol. 2021;84:851-854.
  10. Wang DY, Salem J-E, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4:1721-1728.
  11. Wang Y, Abu-Sbeih H, Mao E, et al. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson. J Immunother Cancer. 2018;6:37.
  12. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: management of immunotherapy-related toxicities. v.1.2023. nccn.org. Accessed May 16, 2023.
  13. Schneider BJ Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39:4073-4126.
  14. Song Y, Fu Y, Xie Q, et al. Anti-angiogenic agents in combination with immune checkpoint inhibitors: a promising strategy for cancer treatment. Front Immunol. 2020;11:1956.
  15. Atezolizumab [prescribing information]. South San Francisco, CA: Genentech; 2022.
  16. Axitinib [prescribing information]. New York, NY: Pfizer; 2022.
  17. Lenvatinib [prescribing information]. Nutley, NJ: Eisai; 2022.
  18. Nivolumab [prescribing information]. Princeton, NJ: Bristol Myers Squibb; 2023.
  19. Pembrolizumab [prescribing information]. Rahway, NJ: Merck Sharp & Dohme; 2023.
  20. Cabozantinib [prescribing information]. Alameda, CA: Exelixis; 2021.
  21. Cheng A-L, Quin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76:862-873.
  22. Makker V, Colombo N, Casado Herraez A, et al. Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): study 309/KEYNOTE-775. Presented at: European Society for Medical Oncology Congress 2022; September 9-13, 2022. Abstract 525MO.
  23. Makker V, Colombo N, Herráez AC, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386:437-448.
  24. Choueri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31:1030-1039.
  25. Burotto M, Powles T, Escudier B, et al. Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate 9ER trial. Presented at: 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16-18, 2023. Abstract 603.
  26. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): results from 42-month follow-up of KEYNOTE-426. Presented at: 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021. Abstract 4500.
  27. Choueri TK, Eto M, Motzer R, et al. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023;24:228-238.
  28. NCCN Kidney. Clinical practice guidelines in oncology: kidney cancer. v.3.2022. nccn.org. Accessed May 16, 2023.
  29. NCCN HCC. Clinical practice guidelines in oncology: hepatocellular carcinoma. v.2.2021. nccn.org. Accessed May 16, 2023.
  30. NCCN Uterine. Clinical practice guidelines in oncology: uterine neoplasms. v.1.2023. nccn.org. Accessed May 16, 2023.
  31. Grünwald V, Voss MH, Rini BI, et al. Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Br J Cancer. 2020;123:898-904.
  32. Vaishampayan U, Schöffski P, Ravaud A, et al. Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019;7:275.
  33. McDermott DF, Lee J-L, Ziobro M, et al. First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): results from KEYNOTE-427 cohort B. Presented at: 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 14-16, 2019. Abstract 546.
  34. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14:1287-1294.
  35. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116-1127.
  36. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103-1115.
  37. Albiges L, Powles T, Staehler M, et al. Updated European Association of Urology Guidelines on renal cell carcinoma: immune checkpoint inhibition is the new backbone in first-line treatment of metastatic clear-cell renal cell carcinoma. Eur Urol. 2019;76:151-156.
  38. Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: the European Society for Medical Oncology Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:1217-1238.
  39. Brahmer JR, Abu-Sbeih H, Antonio Ascierto P, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Imunother Cancer. 2021;9:e002435.
  40. Makker V, Taylor MH, Oaknin A, et al. Characterization and management of adverse reactions in patients with advanced endometrial carcinoma treated with lenvatinib plus pembrolizumab. Oncologist. 2021;26:e1599-e1608.
  41. Motzer R, Alekseev B, Rha S-Y, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384:1289-1300.
  42. Motzer R, George S, Merchan JR, et al. Characterization and management of adverse reactions from the CLEAR study in advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab. Oncologist. 2023;[Epub ahead of print].
  43. Robinson ES, Khankin EV, Karumanchi SA, et al. Hypertension induced by VEGF signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol. 2010;30:591-601.
  44. Wirth LJ, Tahara M, Robinson B, et al. Treatment-emergent hypertension and efficacy in the phase 3 study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). 2018;124:2365-2372.
  45. McGregor B, Mortazavi A, Cordes L, et al. Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: a review. Cancer Treat Rev. 2022;103:102333.
  46. Pirš B, Škof E, Smrkolj V, et al. Overview of immune checkpoint inhibitors in gynecological cancer treatment. Cancers (Basel). 2022;14:631.
  47. Niraparib [prescribing information]. Durham, NC: GlaxoSmithKline; 2023.
  48. Olaparib [prescribing information]. Wilmington, DE: AstraZeneca; 2022.
  49. Rucaparib [prescribing information]. Boulder, CO: Clovis Oncology; 2022.
  50. Vikas P, Borcherding N, Chennamadhavuni A, et al. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol. 2020;10:570.
  51. Banerjee S, Imbimbo M, Roxbrugh P, et al. Phase II study of olaparib plus durvalumab with or without bevacizumab (MEDIOLA): final analysis of overall survival in patients with non-germline BRCA-mutated platinum-sensitive relapsed ovarian cancer. Presented at: European Society for Medical Oncology Congress 2022; September 9-13, 2022. Abstract 529MO.
  52. Drew Y, Kaufman B, Banerjee S, et al. Phase II study of olaparib + durvalumab (MEDIOLA): updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC). Presented at: European Society for Medical Oncology Congress 2019; September 27 - October 1, 2019. Abstract 4563.
  53. Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol. 2019;5:1141-1149.
  54. Liu J, Gaillard S, Hendrickson AW, et al. An open-label phase II study of dostarlimab (TSR-042), bevacizumab (bev), and niraparib combination in patients (pts) with platinum-resistant ovarian cancer (PROC): cohort A of the OPAL trial. Presented at: 2021 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 20-23, 2021. Abstract 24.
  55. Ramalingam SS, Thara E, Awad MM, et al. JASPER: phase 2 trial of first-line niraparib plus pembrolizumab in patients with advanced non-small cell lung cancer. Cancer. 2022;128:65-74.
  56. Thomas A, Vilimas R, Trindade C, et al. Durvalumab in combination with olaparib in patients with relapsed SCLC: results from a phase II study. J Thorac Oncol. 2019;14:1447-1457.
  57. May B. ASCO publishes rapid guideline update on PARP inhibitors in ovarian cancer. ascopost.com/issues/november-25-2022/asco-publishes-rapid-guideline-update-on-parp-inhibitors-in-ovarian-cancer. Accessed May 16, 2023.
  58. Harter P, Trillsch F, Okamoto A, et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): results from the randomized, placebo (pbo)-controlled phase III DUO-O trial. Presented at: 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023. Abstract LBA5506.
  59. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;[Epub ahead of print].
  60. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;[Epub ahead of print].
  61. Yu EY, Park SH, Goh JCH, et al. Pembrolizumab + olaparib vs abiraterone (abi) or enzalutamide (enza) for patients (pts) with previously treated metastatic castration-resistant prostate cancer (mCRPC): randomized open-label phase III KEYLYNK-010 study. Presented at: European Society for Medical Oncology Congress 2022; September 9-13, 2022. Abstract 1362MO.
  62. LaFargue CJ, Dal Molin GZ, Sood AK, et al. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol. 2019;20:e15-e28.
  63. Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21:1155-1164.
  64. González-Martín A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381:2391-2402.
  65. Monk BJ, González-Martin A, Buckley L, et al. Safety and management of niraparib monotherapy in ovarian cancer clinical trials. Int J Gynecol Cancer. 2023;[Epub ahead of print].
  66. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495-2505.
  67. Monk BJ, Parkinson C, Lim MC, et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): a randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Abstract LBA5500.
  68. Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964.
  69. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381:2416-2428.
  70. Hardesty MM, Krivak TC, Wright GS, et al. OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Gynecol Oncol. 2022;166:219-229.
  71. Kiss I, Kuhn M, Hrusak K, et al. Incidence of fatigue associated with immune checkpoint inhibitors in patients with cancer: a meta-analysis. ESMO Open. 2022;7:100474.
  72. Murakami N, Motwani S, Riella LV. Renal complications of immune checkpoint blockade. Curr Probl Cancer. 2017;41:100-110.
  73. Gupta S, Short SAP, Sise ME, et al. Acute kidney injury in patients treated with immune checkpoint inhibitors. J Immunother Cancer. 2021;9:e003467.
  74. Davis EJ, Salem JE, Young A, et al. Hematologic complications of immune checkpoint inhibitors. Oncologist. 2019;24:584-588.
  75. Labadie BW, Morris DS, Bryce AH, et al. Guidelines for management of treatment-emergent adverse events during rucaparib treatment of patients with metastatic castration-resistant prostate cancer. Cancer Manag Res. 2022;14:673-686.
  76. Theriot J, Wermuth HR, Ashurst JV. Antiemetic serotonin-5-HT3 receptor blockers. ncbi.nlm.nih.gov/books/NBK513318. Accessed May 16, 2023.
  77. Umar RM. Drug-drug interactions between antiemetics used in cancer patients. J Oncol Sci. 2018;4:142-146.
  78. Moore KN, Monk BJ. Patient counseling and management of symptoms during olaparib therapy for recurrent ovarian cancer. Oncologist. 2016;21:954-963.
  79. Morice PM, Leary A, Dolladille C, et al. Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: a safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database. Lancet Haematol. 2021;8:e122-e134.