Several new drug therapies-both new drugs and new indications-are now available for various cancers.
Newly diagnosed CD33-positive AML. Gemtuzumab ozogamicin (Mylotarg) is now approved to treat newly diagnosed CD33-positive acute myeloid leukemia (AML) in pediatric patients ages one month and older. Previously, gemtuzumab was approved to treat adults with AML and adults and children with relapsed or refractory CD33-positive AML. The drug is given in combination with standard chemotherapy.
Gemtuzumab is an antibody drug conjugate (ADC) composed of the CD33-directed monoclonal antibody. The drug's anticancer activity is believed to be due to the binding of the ADC to CD33-expressing tumor cells, eventually leading to double-strand DNA breaks, cell cycle arrest, and programmed cell death.
The safety and efficacy of gemtuzumab in children were determined in a multicenter randomized study of 1,063 patients with newly diagnosed AML between the ages of birth to 29 years. Patients received either five-cycle chemotherapy alone or with gemtuzumab. The percentage of patients who were free of induction failure, relapse, or death at five years was greater in those who received chemotherapy with gemtuzumab compared with those who received chemotherapy alone (48% versus 40%).
Adverse effects are similar to those previously noted, with the labeling containing a boxed warning for hepatotoxicity, including veno-occlusive liver disease (also called sinusoidal obstruction syndrome), which can be fatal. Other serious adverse effects include hemorrhage, infusion-related reactions, and embryo-fetal toxicity. The most common adverse effects are infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.
Nurses should read the package insert for full dosing information. Nurses should also carefully measure pediatric patients' height in centimeters and weight in kilograms and calculate their body surface area to determine an accurate dose. Patients should be assessed carefully for adverse effects.
Health care professionals should report all suspected serious adverse effects of gemtuzumab to MedWatch, the Food and Drug Administration (FDA) safety information and adverse event reporting program: http://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-repo.
For complete prescribing information for gemtuzumag, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761060s004lbl.pdf.
Metastatic small cell lung cancer. The FDA has granted accelerated approval to lurbinectedin (Zepzelca) to treat adults with metastatic small cell lung cancer (SCLC) who have disease progression on or after platinum-based chemotherapy.
Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix toward the major groove. The grooves are important for the attachment of DNA-binding proteins involved in replication and transcription. Adducts are a form of DNA damage that can cause mutations and lead to cancers. Alkylating agents, like lurbinectedin, destabilize the DNA helix and interfere with DNA repair, replication, and transcription. In binding the guanine residues, Lurbinectedin creates a cascade of events that affect how DNA binds proteins, ultimately resulting in a disrupted cell cycle and eventually cell death.
Lurbinectedin's efficacy was determined in a multicenter, open-label, multicohort trial of 105 patients with metastatic SCLC that had progressed despite their receiving platinum-based chemotherapy. The FDA's accelerated approval was based on an overall response rate of 35% and the duration of the response (median duration, 5.3 months). The drug will need to be studied further in order to verify its clinical benefit and continue its approval.
Serious adverse effects include myelosuppression, hepatotoxicity, and embryo-fetal toxicity. The most common adverse reactions were laboratory abnormalities (myelosuppression; increased levels of creatinine, alanine aminotransferase, glucose, and aspartate aminotransferase; decreased levels of albumin, sodium, and magnesium), fatigue, nausea, decreased appetite, musculoskeletal pain, constipation, dyspnea, vomiting, cough, and diarrhea.
Nurses preparing to administer lurbinectedin should check for drug interactions using a drug database. Strong or moderate inhibitors or inducers of the cytochrome P-450 (CYP) isoenzyme CYP3A (which increase or decrease the circulating level of lurbinectedin, respectively) should not be coadministered with lurbinectedin. Nurses should confirm that preinfusion medications for antiemetic prophylaxis, such as corticosteroids or serotonin antagonists, have been ordered for the patient. To determine that the correct dose of lurbinectedin was ordered, nurses should determine the patient's body surface area and use the formula in the drug's labeling to calculate the required volume of reconstituted solution.
For complete prescribing information for lurbinectedin, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213702s000lbl.pdf.
MSI-H/dMMR metastatic colorectal cancer. Pembrolizumab (Keytruda), a programmed death receptor-1-blocking monoclonal antibody, is now approved to treat unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. About 5% of patients with metastatic colorectal cancer have these types of tumors, which alter the repair of cellular DNA. Pembrolizumab is the first immunotherapy approved for this use as a first-line, sole treatment. It has been approved to treat various other cancers since 2014, but for many applications it is used in conjunction with chemotherapy.
Approval of pembrolizumab is based on one multicenter, open-label, active-controlled, randomized trial of 307 patients that compared progression-free survival in those receiving pembrolizumab and those receiving chemotherapy. Patients receiving pembrolizumab had a median progression-free survival of 16.4 months, compared with 8.2 months for those receiving chemotherapy.
Adverse effects of pembrolizumab for this new indication are similar to those observed for previous indications. Immune-mediated adverse effects include pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Infusion reactions and embryo-fetal toxicity are also possible. The most common adverse effects are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, fever, cough, dyspnea, constipation, pain, and abdominal pain.
Nurses should confirm the availability of a patent IV line prior to infusion. They should assess for infusion-related reactions and stop the infusion if one occurs; permanent discontinuation is indicated if severe or life-threatening reactions occur. Women of childbearing age should use effective birth control, as fetal harm is possible.
For complete prescribing information for pembrolizumab, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s084lbl.pdf.
Diffuse large B-cell lymphoma. Selinexor (Xpovio) has been granted accelerated approval to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two different systemic therapies. Previously, selinexor was approved to treat relapsed or refractory multiple myeloma when given with dexamethasone.
Selinexor is a nuclear export inhibitor and reversibly inhibits nuclear export of tumor suppressor proteins, growth regulators, and messenger RNAs of oncogenic proteins by blocking exportin 1 (which is involved in several cellular processes).
Because the use of selinexor to treat DLBCL was granted under accelerated approval based on response rate, additional studies will be needed to verify the drug's efficacy; selinexor could be withdrawn from the market if it is not found to be clinically effective. Selinexor's efficacy was evaluated in a multicenter, single-arm, open-label study of 134 adults with relapsed or refractory DLBCL who had received two to five previous treatment regimens. Efficacy was determined by overall response rate and duration of response. Eighteen (13%) patients had a complete response to selinexor and 21 (16%) had a partial response. Of those who had a response, 56% maintained it for three months, 38% for six months, and 15% for 12 months.
Label warnings and precautions for selinexor include thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infections, neurological toxicity, and embryo-fetal toxicity. The most common adverse effects in patients with DLBCL are fatigue, nausea, diarrhea, loss of appetite, weight loss, constipation, vomiting, and pyrexia. Common, serious laboratory abnormalities include thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.
Nurses working with patients prescribed selinexor should encourage them to remain hydrated by drinking plenty of fluids and to eat nutrient-rich foods high in calories to maintain sufficient caloric intake during treatment. The drug should be swallowed whole with water. As nausea and vomiting are common with selinexor, prophylactic antiemetics are recommended. Nurses should carefully assess the patient's laboratory values for changes indicating adverse effects. Patient education should include the rationale for repeated laboratory tests, and the signs and symptoms of adverse effects.
For complete prescribing information for selinexor, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212306s001lbl.pdf.