Biosimilars, Oral Agents, and Drugs Targeting Genetic Mutations Are Creating a Paradigm Shift in Cancer Treatment

Many of the newly U.S. Food and Drug Administration (FDA)-approved agents received expedited approval, meaning far fewer patients were observed under a rigorous clinical trial environment; therefore, it’s more critical than ever that nurses share the adverse events they identify for patients on these agents. Through ONS’s Recognize It; Report It campaign, nurses can understand how to report adverse events to providers for appropriate management and to FDA for widespread dissemination to prescribers and practitioners. Learn more at ons.org/toolkits/recognize-it-report-it.  

Identified Genetic Mutations

Cancer care is in a fundamental shift from disease-focused drugs to tumor marker or genetic mutation focused. One example is larotrectinib, which is approved for any solid organ malignancy (https://voice.ons.org/news-and-views/fda-approves-larotrectinib-for-solid-tumors-with-ntrk-gene-fusions) that expresses a neurotrophic receptor tyrosine kinase (NTRK) gene fusion, rather than a specific diseases site.

• Patients first require specialized FISH or next-generation sequence testing to determine the presence of a NTRK gene fusion.
• The approval is for both pediatric and adult patients who have progressed following systemic therapy for their disease type and those for whom surgery is not feasible. 
• Recommended dosing is 100 mg orally twice daily for adults and 100 mg/m² orally twice daily for pediatric patients. 
• Most common side effects include fatigue, nausea, dizziness, vomiting, cough, diarrhea, and elevated liver enzymes.

Hematologic Malignancies

• Brentuximab vedotin in combination with chemotherapy for untreated systemic anaplastic large cell lymphoma (https://voice.ons.org/news-and-views/fda-approves-brentuximab-vedotin-for-previously-untreated-salcl-and-cd30-expressing) or other CD30+ peripheral T-cell lymphoma.
  • This is the first approval for previously untreated peripheral T-cell lymphoma and was associated with increased overall survival and progression free survival. In clinical trials, brentuximab vedotin was combined with the CHOP chemotherapy regimen.
  • Dosing is 1.8 mg/kg (not to exceed 180 mg) every three weeks for six to eight doses with G-CSF initiated at cycle one.
  • Most common adverse events observed when adding brentuximab vedotin to CHOP were nausea, diarrhea, fatigue, mucositis, pyrexia, vomiting, and anemia. Incidence of peripheral neuropathy may also be slightly higher than with CHOP alone. 

• Glasdegib for adults aged 75 or older with acute myeloid leukemia (AML) (https://voice.ons.org/news-and-views/fda-approves-glasdegib-for-aml-in-adults-aged-75-or-older-or-who-have-comorbidities) and multiple comorbidities
  • Older adults with comorbidities that preclude them from receiving intensive chemotherapy may be prescribed glasdegib in combination with low-dose cytarabine (LDAC).
  • Recommended dosing for glasdegib is 100 mg orally. For patients randomized to the combination treatment, LDAC was administered 20 mg subcutaneously twice daily on days 110 of a 28-day cycle. 
• Gilteritinib for relapsed or refractory AML with an FLT3 mutation (https://voice.ons.org/news-and-views/fda-approves-gilteritinib-for-relapsed-refractory-aml-with-an-flt3-mutation)
  • Adults with relapsed or refractory acute myeloid leukemia who are FLT3 positive may be prescribed gilteritinib. Clinical trials saw reduced transfusion dependence.
  • Recommended dosing is 120 mg orally once daily.
  • Most common adverse events were myalgia, elevated liver function tests, fatigue, fever, diarrhea, dyspnea, edema, and rash.
• Rituximab-abbs as a biosimilar to rituximab (https://voice.ons.org/news-and-views/fda-approves-rituximab-abbs-as-biosimilar-to-rituximab-for-non-hodgkins-lymphoma) for non-Hodgkin lymphoma
  • Rituximab-abbs represents the first biosimilar approval for rituximab for patients with CD20-positive B-cell non-
    Hodgkin lymphoma. Rituximab-abbs can be used as single-agent or combination therapy. 
  • Recommended dosing for rituximab-abbs mirrors that of rituximab. Rituximab-abbs is approved as a biosimilar but not an interchangeable product, so dispensing pharmacists may not replace a rituximab order with rituximab-abbs. 
  • The most common side effects were infusion reactions, fever, lymphoma, chills, infection, and asthenia.   

Hepatocellular Carcinoma

• Pembrolizumab for hepatocellular carcinoma (https://voice.ons.org/news-and-views/fda-grants-accelerated-approval-to-pembrolizumab-for-hepatocellular-carcinoma)
  • The indication is for patients who have failed or were intolerant of sorafenib, have measurable disease, and have apparent liver impairment. In clinical trials, patients with autoimmune disease, hepatitis, or ascites or those on immunosuppression were ineligible for enrollment.
  • Dosing is 200 mg via IV over 30 minutes every three weeks.
  • Most common side effects observed were consistent with other studies involving pembrolizumab and include ascites and immune-mediated hepatitis.   

Lung Cancer

• Lorlatinib for second- and third-line treatment (https://voice.ons.org/news-and-views/fda-approves-lorlatinib-for-second-third-line-treatment-of-alk-positive-metastatic) of ALK-positive metastatic non-small cell lung cancer
  • Patients must be ALK-positive and failed crizotinib and at least one other ALK inhibitor.
  • Dosing is currently standardized at 100 mg orally once a day
  • The most common adverse events (> 20%) were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. 

Cancer Prevention

In December 2018, FDA expanded approval (https://voice.ons.org/news-and-views/hpv-9-valent-vaccine-approved-for-people-aged-27-45) of the human papillomavirus (HPV) 9-valent vaccine to people aged 27–45. The vaccine is about 88% effective in preventing HPV infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to the nine HPV types. Oncology nurses are paramount in educating patients about options for primary prevention of first or subsequent cancers.