According to the latest American Cancer Society (ACS) Cancer Statistics 2016 report, the incidence of lung cancer has decreased 38% and 13% among men and women, respectively, because of reduced tobacco use. However, it remains the leading cause of cancer death in older adults of both genders.

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for 85%–95% of diagnoses. Its prognosis is usually poor because more than half of cases are diagnosed in later stages. Five-year survival rates are as low as 5% for stage IIB and 1% for stage IV. However, new targeted therapies have emerged in recent years that show promise to increase the survival rate for certain NSCLC mutations.

In their article in the December 2015 issue of the Clinical Journal of Oncology Nursing, Kreamer and Riordan provided an overview of two types of drugs that target epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in NSCLC. They discussed side effects of the drugs and ways nurses can help patients manage them.

EGFR Inhibitors for NSCLC

Kreamer and Riordan explained that gefitinib and erlotinib are oral, first-generation EGFR tyrosine kinase inhibitors (TKIs). When first introduced in 2003 and 2004, respectively, success rates were low. However, more recently researchers discovered the two drugs are more effective when NSCLC tumors express mutations in the EGFR gene (del19 and exon 21 L858R). As a result, erlotinib is now approved as (a) first-line treatment for metastatic NSCLC harboring del19 or exon 21 L858R and as (b) maintenance therapy in patients with advanced NSCLC whose disease has not progressed after four cycles of platinum-based, first-line chemotherapy. Similarly, gefitinib is now approved for the first-line treatment of patients with NSCLC with del10 or exon 21 L858R substitution mutations.

Finally, a newer EGFR inhibitor, afatinib, was approved in 2013 as first-line treatment of metastatic NSCLC harboring del19 or exon 21 L858R. Afatinib is an irreversible EGFR TKI, which researchers hypothesize may help overcome the drug resistance that often develops with gefitinib and erlotinib, which are reversible EGFR inibitors, but Kreamer and Riordan emphasized that more evidence is needed to support that theory.

Nursing Management of Common EGFR Inhibitor Adverse Events

The most common adverse events reported with erlotinib and afatinib are highlighted in Figure 1.

Figure 1. Common Adverse Events From EGFR and ALK Inhibitors

EGFR Inhibitors

Erlotinib

  • Rash
  • Diarrhea
  • Dyspnea
  • Anorexia
  • Fatigue
  • Cough
  • Nausea

Afatinib

  • Diarrhea
  • Rash or dermatitis acneiform
  • Stomatitis
  • Paronychia
  • Dry skin
  • Elevated ALT or AST
  • Hypokalemia

ALK Inhibitors

Crizotinib

  • Vision disorders
  • Diarrhea
  • Nausea
  • Vomiting
  • Constipation
  • Edema
  • Elevated ALT or AST
  • Lymphopenia
  • Neutropenia
  • Hypophosphatemia
  • Hypokalemia

Ceritinib

  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Fatigue
  • Decreased appetite
  • Decreased hemoglobin
  • Elevated ALT or AST
  • Elevated creatinine, glucose, lipase, or total bilirubin
  • Decreased phosphate

Rash: Kreamer and Riordan noted that rashes are more easily managed preventatively, before EGFR inhibitor treatment begins. Nurses should instruct patients on lifestyle recommendations (e.g., protecting from sun exposure, using moisturizers) and have them begin a prophylactic treatment regimen. When a rash develops, nurses should assess the severity and advocate for an EGFR inhibitor dose reduction if necessary.

Diarrhea: When patients report this side effect, Kreamer and Riordan advised that nurses should assess them to rule out other causes. If the adverse event is attributed to the EGFR, start patients on the BRAT (bananas, rice, applesauce, and toast) diet, ensure adequate fluid intake, and administer a standard loperamide dose. If the symptom doesn’t resolve, nurses should assess the severity and increase the loperamide dose. Providing IV fluids, reducing the EGFR inhibitor dose, or treating with octreocide may be necessary.

ALK Inhibitors for NSCLC

According to Kreamer and Riordan, about 4% of NSCLC involves ALK gene rearrangements. Crizotinib and ceritinib are two oral ALK inhibitors approved for use in ALK-positive NSCLC in 2011 and 2014, respectively. Ceritinib is used in patients who have progressed on or are intolerant to crizotinib.

Nursing Management of Common ALK Inhibitor Adverse Events

The most common side effects of ALK inhibitors are also highlighted in Figure 1. Of note, visual disturbances and gastrointestinal effects with crizotinib tend to begin within two weeks of starting therapy and then improve over time as treatment continues. 

Gastrointestinal effects: Kreamer and Riordan noted that dose modifications may be necessary to control gastrointestinal side effects from AKL inhibitors. Nurses can use the strategies previously mentioned for EGFR inhibitors to manage diarrhea, but if it does not resolve, dose modifications may be required. To prevent treatment-related nausea, patients should predose with an antiemetic. 

The authors also emphasized that ceritinib must be taken on an empty stomach (two hours after and two hours before food). To accommodate that requirement, patients may take it at night before bed, at which time they may need to predose with loperamide to prevent the occurrence of loose stools or diarrhea overnight. The antispasmodic dicyclomine may be used for abdominal pain attributed to ceritinib. Finally, Kreamer and Riordan reported that for severe gastrointestinal effects that persist despite treatment, ceritnib may be withheld and then resumed at a lower dose.

Identifying Candidates for EGFR and ALK Inhibitors

Kreamer and Riordan emphasized that these promising new therapies were beneficial only in patients whose cancers involved the specific pathways that the drugs targeted. EGFR mutations account for only 15% of primary lung cancers and are more likely to occur in East Asian patients, women, never smokers, and patients with adenocarcinomas. ALK rearrangements occur in only 2%–6% of NSCLC and more often present in younger patients and those with little or no smoking history. 

The current standard of care, Kreamer and Riordan noted, is to perform molecular testing for all patients with adenocarcinomas and mixed lung cancers with an adenocarcinoma component. As the primary patient educators, oncology nurses need to ensure that patients undergoing testing understand the low likelihood of a positive result. Additionally, even after testing positive, patients must understand that the new treatments are not curative and that their cancers are eventually expected to develop resistance.

Finally, like many new oral therapies, the agents can be associated with a high out-of-pocket cost for patients, depending on their insurance coverage. Nurses should be able to refer patients to pharmaceutical companies’ assistance programs when needed.

For more information on EGFR and ALK inhibitors for NSCLC, refer to the full article by Kreamer and Riordan.

Five-Minute In-Service is a monthly feature that offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Targeted Therapies for Non-Small Cell Lung Cancer: An Update on Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Inhibitors,” by Kristen Kreamer, CRNP, MSN, AOCNP®, APRN-BC, and Debbie Riordan, RN, BS, which was featured in the December 2015 issue of CJON. Questions regarding the information presented in this Five-Minute In-Service should be directed to the CJON editor. Photocopying of this article for educational purposes and group discussion is permitted.