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Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit

Acknowledgment of Commercial Support

This activity is supported by educational grants from AstraZeneca, Helsinn Therapeutics (U.S.), Inc. and Novartis Pharmaceuticals Corporation.


Community Practice Connections™: 1st Annual School of Nursing Oncology™ PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


 

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PER Pulse™ Recap

The incidence of skin cancer in the United States continues to climb, and melanoma accounts for most skin cancer-related mortality. Although melanoma lesions are often caught early and can be surgically excised, the treatment of advanced melanoma has historically been a significant clinical challenge.1 As our understanding of the role of abnormal cell signaling pathways and specific genetic mutations in the pathogenesis of melanoma has evolved, new treatments such as those that enhance the immune response and those that inhibit cellular proliferation have emerged.2 Nurses play a pivotal role in educating their patients regarding treatment therapies, as well as addressing potential side effects and setting treatment expectations.

Anti–CTLA-4 antibodies and anti–PD-1 antibodies have been studied extensively in the treatment of melanoma.3-5 New combinations have also been studied, and immune-related adverse events must be taken into consideration when selecting systemic therapy for patients with advanced melanoma. BRAF and MEK inhibitors have gained approval for the treatment of patients with advanced melanoma with certain BRAF mutations.5-8

Other agents have been studied for intralesional therapy for melanoma. Two of the more commonly used intralesional agents are talimogene laherparepvec, which uses a modified herpes simplex virus to attack tumors and deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) to injected lesions, and interleukin-2, which has been studied extensively.9 Although new treatment options such as immunotherapy and targeted therapy have improved outcomes for patients with metastatic melanoma, treatment of patients with this disease remains an active area of clinical investigation. Nurses involved in the care of patients with melanoma must continue to remain aware of new treatment options that may offer improved efficacy and less toxicity. In this segment, Grace Cherry discusses recent advancements in the treatment of advanced melanoma and considerations for supportive care for different treatment options.

References

  1. Korn EL, Liu PY, Lee SJ, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008;26(4):527-534. doi: 10.1200/JCO.2007.12.7837.
  2. Vennepureddy A, Thumallapally N, Motilal Nehru V, et al. Novel drugs and combination therapies for the treatment of metastatic melanoma. J Clin Med Res. 2016;8(2):63-75. doi: 10.14740/jocmr2424w.
  3. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480-489. doi: 10.1038/nature10673.
  4. Robert C, Schacter J, Long GY, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521-2532. doi: 10.1066/NEJMoa1503093.
  5. Larkin J, Chiarion Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34. doi: 10.1056/NEJMoa1504030.
  6. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-1888. doi: 10.1056/NEJMoa1406037.
  7. Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867-1876. doi: 10.1056/NEJMoa1408868.
  8. NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 1. 2017. https://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf.
  9. Nouri N, Garbe C. Intralesional immunotherapy as a strategy to treat melanoma. Expert Opin Biol Ther. 2016;16(5):619-626. doi: 10.1517/14712598.2016.

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PER Pulse™ Recap

Non-Small-Cell Lung Cancer: Treatment Considerations and Management Strategies

As treatment options for patients with non-small-cell lung cancer (NSCLC) are becoming more personalized with the advent of targeted therapies, oncology nurses play a key role in the timely identification and management of adverse events (AEs) associated with these therapies, as well as other treatment modalities such as chemotherapy. Timely interventions may improve patient outcomes and facilitate adherence to treatment protocols.

Several targeted therapy options have been approved for patients with NSCLC. Patients with NSCLC who have EGFR mutations may have greater sensitivity to treatment with tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib.1 Osimertinib is recommended as a second and later line of therapy for patients who have the EGFR T790M mutation who have progressed on earlier TKI therapy.1 Several toxicities have been reported with EGFR inhibitors, and the most common of these is rash.2 Multinational Association of Supportive Care in Cancer recommendations for the treatment of rash associated with EGFR inhibitors include topical alclometasone, fluocinonide, or clindamycin. Systemic options include doxycycline, minocycline, and isotretinoin.3 Diarrhea is also not uncommon with the use of EGFR inhibitors. Other toxicities associated with EGFR inhibitors include interstitial lung disease/pneumonitis, cardiomyopathy, and transaminitis.

ALK inhibitors such as alectinib, brigatinib, ceritinib, and crizotinib have also been approved for the treatment of patients with NSCLC, and carry their own toxicity profiles. Common toxicities associated with the use of crizotinib include visual changes, including difficulty with light and dark accommodation. Other common toxicities, include vomiting, diarrhea, and edema. Ceritinib carries significant challenges with gastrointestinal-related AEs, including diarrhea, nausea, and vomiting.4 Fatigue is also commonly seen with ceritinib use.4 In clinical trials, brigatinib was shown to have a relatively high incidence of interstitial lung disease early in the treatment course; treatment is initiated with a 7-day period of 90 mg daily, followed by 180 mg daily.

BRAF/MEK inhibitor combinations have been associated with pyrexia.
One of the most worrisome toxicities for patients is the emergence of chemotherapy-induced nausea and vomiting (CINV). According to recent National Comprehensive Cancer Network guidelines, carboplatin AUC ≥4, any regimen with an anthracycline and cyclophosphamide, and cisplatin have all been classified as highly emetogenic chemotherapy.5 Regimens with carboplatin AUC less than 4 are moderately emetogenic.

Serotonin receptor antagonists and neurokinin-1 receptor antagonists are key classes of antiemetic therapy used in the treatment of CINV. Other classes of therapy include corticosteroids, benzodiazepines, dopamine receptor antagonists, and cannabinoids. Newer agents include the combination of a neurokinin 1 receptor antagonist (netupitant) and a serotonin receptor antagonist (palonosetron). The combination of these two medicines and dexamethasone has been studied extensively and shown improvement in complete response to CINV compared with the combination of palonosetron and dexamethasone.6 Another newer agent that has emerged is a long-acting formulation of granisetron, used in the prevention of acute and delayed CINV. Olanzapine has historically been used as an atypical antipsychotic, but recent studies have established its efficacy in the treatment of CINV.6

Utilization of clear written instructions on how to take prophylactic and as needed antiemetics can be beneficial, as well as maintaining a record of CINV between office visits. Patient navigation, home telehealth, and nurse care management are commonly used, and care coordination increases the odds of appropriate health care use.7 In this segment, Beth Eaby-Sandy discusses management of side effects associated with cancer treatments, including chemotherapy and targeted therapies for NSCLC.
References

  1. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 8. 2017. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
  2. Lacouture ME. Mechanisms of cutaneous toxcities to EGFR inhibitors. Nat Rev Cancer. 2006;6(10):803-812.
  3. Lacouture ME. Anadkat MJ, Bensadoun RJ, et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19(8):1079-1095. doi: 10.1007/s00520-011-1197-6.
  4. Cho BC, Kim DW, Bearz A, et al. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017;12(9):135701367. doi: 10.1016/j.jtho.2017.07.005.
  5. NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Version 2. 2017. https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf.
  6. Jordan K, Jahn F, Aapro M. Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann Oncol. 2015;26(6):1081-1090. doi: 10.1093/annonc/mdv138.
  7. Gorin SS, Haggstrom D, Han PKJ, et al. Cancer care coordination: a systematic review and meta-analysis of over 30 years of empirical studies [published online July 6, 2017]. Ann Behav Med. doi: 10.1007/s12160-017-9876-2.

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PER Pulse™ Recap

Advancements in the Management of Gastrointestinal and Genitourinary Cancers

Gastrointestinal Cancers

Several new treatment choices have emerged for patients with metastatic colorectal cancer (mCRC), with the approval of capecitabine, oxaliplatin, irinotecan, anti-EGFR monoclonal antibodies, anti-VEGF agents, regorafenib, and trifluridine/tipiracil. Clinical studies have confirmed the efficacy of these treatment options, as well as contributed to the identification of potential adverse events that must be addressed in a timely fashion.1-4

New treatment strategies and therapeutic options continue to emerge at a rapid pace. For patients with RAS wild-type cancer with left-sided tumors, EGFR antibodies may be a viable option.3 Patients who are symptomatic and need response may derive benefit from reinduction or rechallenge with oxaliplatin.1 Options such as tifluridine/tipiracil have expanded treatment options, even in those with reduced performance status. Sequential treatment with regorafenib and trifluridine/tipiracil may also be appropriate for patients with good performance status.

Genitourinary Cancers

The treatment paradigm for different genitourinary cancers also continue to evolve at a rapid pace, with new treatment options and clinical evidence presenting the potential to improve outcomes for patients with prostate, renal, and urothelial/bladder cancers. To begin with, patients with metastatic prostate cancer have been the subject of several recent studies that have addressed the addition of docetaxel or abiraterone to androgen deprivation therapy, such as CHAARTED, LATITUDE, and STAMPEDE.5-7 These studies have shown an overall survival benefit relative to androgen-deprivation therapy alone. 

For patients with renal cancer, there has been a great expansion of treatment options over the past decade, with the incorporation of agents targeting VEGF (axitinib, bevacizumab, pazopanib, and sunitinib), as well as agents targeting the mammalian target of rapamycin pathway (everolimus, temsirolimus).8 The phase III METEOR study compared cabozantinib with everolimus in the treatment of patients with advanced renal cell carcinoma (RCC) who had disease progression on prior VEGFR-TKI therapy. This study found that patients treated with cabozantinib had a significantly higher response rate (17% versus 3%; P<.0001), greater progression-free survival (7.4 versus 3.9 months; P = .00026), and overall survival (21.4 months versus 16.5 months; P<.0001).9 The phase II CABOSUN study compared cabozantinib versus sunitinib in the treatment of patients with advanced RCC, including patients with IMDC intermediate or poor risk. This study showed significant clinical improvement in progression free survival and objective response rate in the group treated with cabozantinib compared with patients who received sunitinib.10

Immunotherapy with checkpoint inhibitors has significantly changed the treatment paradigm for patients with bladder cancer. Monoclonal antibodies targeting PD-1 such as nivolumab and pembrolizumab, as well as its ligand PD-L1 (atezolizumab, avelumab, and druvalumab) have all been approved for patients with metastatic bladder cancer. In this segment, Laura Wood discusses recent advancements in the treatment of genitourinary malignancies.

References

  1. Vogel A, Hofheinz RD, Kubicka S, Arnold D. Treatment decisions in metastatic colorectal cancer – beyond first and second line combination therapies. Cancer Treat Rev. 2017;59:54-60. doi: 10.1016/j.ctrv.2017.04.007.
  2. Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. doi: 10.1056/NEJMoa1414325.
  3. Allegra CJ, Rumble RB, Hamilton SR, et al. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology provisional clinical opinion update 2015. J Clin Oncol. 2016;34(2):179-185. doi: 10.1200/JCO.2015.63.9674.
  4. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9683):303-312. doi: 10. 1016/S0140-6736(12)61900-X.
  5. Sweeney CJ, Chen Y, Liu, G, et al. 720PD - Long term efficacy and QOL data of chemohormonal therapy (C-HT) in low and high volume hormone naïve metastatic prostate cancer (PrCa): E3805 CHAARTED trial. Poster presented at  ESMO 2016 Congress; October 7-11, 2016; Copenhagen, Denmark. https://cslide.ctimeetingtech.com/library/esmo/browse/search/M8i#2z94H0EF Abstract 720PD. Accessed September 16, 2017.
  6. James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351. doi: 10.1056/NEJMoa1702900.
  7. Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174.
  8. Rodriguez-Vida A, Hutson TE, Bellmunt J, Strojbos MH. New treatment options for metastatic renal cell carcinoma. ESMO Open. 2017;2(2):e000185. doi: 10.1136/esmoopen-2017-000185.
  9. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3.
  10. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol. 2017;35(6):591-597. doi: 10.1200/JCO.2016.70.7398.




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