ILCNG Article Competition

“Inhibiting Lung Cancer, think inside the cell”

I share a vision.
"Ireland will have a system of cancer control which will reduce our cancer incidence, morbidity and mortality rates relative to other EU15 countries by 2015. Irish people will know and practice health promoting and cancer-preventing behaviours and will have increased awareness of and access to early cancer detection and screening. Ireland will have a network of equitably accessible state-of-the-art cancer treatment facilities and we will become an internationally recognised location for education and research into all aspects of cancer."
Cancer Control Strategy 2006

Introduction
I, like all nurses am committed to achieving excellent services for patients. But we do not do it alone and everyone’s contribution to achieving the big vision is welcome and important. From the bench to the bedside the multi-professional team I believe share this vision.

Patients arrive to specialist cancer centres every day all across Ireland for treatment for their lung cancer, some are post-op and adjuvant, others have stage IV disease. All are hopeful.

“The surgeon said it has all gone nurse, the chemo is just for insurance”
“It has come back nurse, but I’ll fight it again”
“I need more chemo, I need more radiotherapy.”

These will be familiar sentiments to nurses working in oncology. Chemotherapy and radiotherapy schedules are well understood by staff and are explained daily to patients and relatives. Targeted therapies are now also common methods in treating this disease but are we as knowledgeable when explaining these drugs regimes to patients? Does our knowledge have gaps?

How about community pharmacists, who are often the most accessible healthcare professionals to patients, are they meeting patients with questions about these drugs? Public health nurses provide vital community support for patients. Do these professionals have educational needs also?

This article aims to explore the benefits and challenges of small molecule tyrosine kinase inhibitors (TKI’s) It will attempt to provide a learning opportunity for all professionals caring for patients with lung cancer who have been prescribed a TKI.

Then and now
I started my oncology career working with patients with lung cancer over 15 years ago. Targeted therapies such as Erlotininb, Gefitinib, Afatinib and Crizotinib were less well known then if at all. Patients had surgery, chemotherapy and radiotherapy in varying combinations depending on their disease stage. This is still so, but scientific research has developed new drugs which target specific cell activities and these are now part of the lung cancer treatment arena.

Scientific evidence and discussion about tyrosine kinase inhibitors, EGFR directed mutations or angiogenesis inhibition has evolved and is now common among oncology nurses and particularly for those working in the area of NSCLC. Understanding of these concepts is growing but is it robust enough for the patient who asks;
Is there a target for my type of cancer?

Keeping abreast of new agents and clinical trials is a challenge. “Mabs” and “Ibs’ seem to be growing in numbers and coming onto the market very quickly. Medical oncology conferences are generally about new targets. Surgical and radiotherapy techniques are also advancing but development of new chemotherapy agents less so.

ASCO 2014 in its lung cancer roundup discusses overcoming resistance to targeted therapies! Already! Just as we are learning how they work the next wave of research is developing next generation inhibitors for next generation mutations! Updates and highlights are needed constantly.

Benefits and Challenges
A frequent advantage boasted of targeted therapies for NSCLC is that most of the small molecule TKI’s are administered orally. Cancer Information Support Network, 2006 describes how patients will spend less time in oncology units and won’t suffer intravenous discomfort or risks. This is extremely important especially in the context of a group of patients who may have advanced disease and grim prognoses. Patients can have these sophisticated drugs at home. This offers improved quality of life for the patient and reduced costs for them and their hospital. Side effects from targets are perceived to be less toxic generally although this is changing. Clinical trials have shown positive results for patients and these are clear advantages.

“The research team found that erlotinib did help stop the cancer growing in some people, but that it didn’t always help people live longer. They found that erlotinib worked better for those who developed a rash during treatment”
Cancer Research U.K

“Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both”
Journal of Clinical Oncology 2013

“Gefitinib Improves Progression-free Survival for Metastatic Lung Cancers with EGFR Mutations”
NCI Cancer Bulletin.

“Results from an international phase III trial show that crizotinib (Xalkori®) may benefit previously treated patients with advanced lung cancer whose tumors have a specific genetic mutation.”
New England Journal of Medicine 2013

So what are the challenges?

Costs
Unfortunately costs to the state for these drugs are very high. High-tech drug costs for the top 10 TKI’s in 2012 exceeded 20,000,000€. Not all of these were for lung cancer but overall TKI’s are expensive. (Primary Care Re-imbursement Service-Analysis of Claims 2012)

Adherance
“Drugs don’t work in patients who don’t take them!” C.Everett Koop M.D
Patients have increased responsibility over their treatment and compliance is crucial. The BNF 2010 emphasises how important it is for patients to be clear about the purpose, side effects or even how to take their medicines or poor compliance can follow. Agreement between the prescriber and the patient on desired health outcomes should be reached. It recognises that time is needed to explain potential side effects to patients and their families and how pharmacists re-enforce the instructions given by the direct healthcare team.

I have had experience of patients not even collecting their prescriptions! The importance of knowing our patients personality and abilities needs to be considered when prescribing any medication but is clearly crucial with targeted therapies as the impact of non-adherence may be very serious for NSCLC. It is also important to establish who the medication manager is for a patient as oftentimes it is a relative. Accurate, clear instructions about the daily administration of a specific target are required from all professionals meeting the patient or their relative to avoid poor outcomes. When? With or without food? Forgetting a dose? All this needs to be explained.

Side effects
Lung cancer has seen the arrival of many small molecule TKI’s working inside the cancer cell on a pathway or mutation, e.g the EGF receptor. Some key points are explained in the grid below to help clarify some points.

  Generic Trade Target Indictions Handling

Erlotinib

Tarceva

TKI/EGFR

Metastatic or locally advanced NSCL with EGFR mutations

PO OD 1hr before or 2 hrs After food

Afatinib

Gilotrif

TKI/EGFR

Metastatic or locally advanced NSCL with EGFR mutations

PO OD with water , no food 3 hrs before or 1 hour after

Gefitinib

Iressa

TKI/EGFR

Metastatic or locally advanced NSCL with EGFR mutations

PO OD +/- food

Crizotinib

Xalkori

ALK + tumours (ALK test required)

Advanced NSCLC

PO BD +/- food (Avoid grapefruit)

Ceritinib

Zykadia

ALK + tumours

Advanced NSCLC

Awaiting EU approval

Side effects include:

  • Skin toxicities
  • Diarrhoea and other G.I disturbances
  • Electrolyte changes K+ MgSO4
  • Hyperglycaemia
  • Hyperlipidaemia
  • Mucosal changes
  • Hypertension
  • ATE events
  • Cardiac toxicities
  • Wound healing
  • Bowel perforation
  • ILD
  • Proteinuria

This list of potential side effects challenges the perception that oral anti-cancer medications are less complicated to manage than standard I.V chemotherapies.
“I’m only on tablets nurse”

Education provided to patients needs to be as structured and as thorough as that given to patients requiring chemo, radiation. Many nurse-led oral clinics are emerging around the country as this need has been identified, but at present no national guidelines on the management and handling of targeted therapies exist.

Context
So far, I have avoided the gloomy statistics on lung cancer and have chosen to concentrate on targeted therapies. I see them as hopeful new treatments for a difficult disease. The oral route has clear advantages and challenges. Managing toxicities is also challenging and as these drugs are prescribed more, both improvements in care and new toxicities will possibly emerge.

The development of National Skin Toxicity guidelines for anti-EGFR treatments is an example of the commitment of Irish nurses, doctors, pharmacists and pharma personnel to improve quality of life for patients and constructively manage difficult side effects.

Where do the new agents fit in the overall picture of lung cancer management?

At present these drugs are mainly life prolonging options in patients with advanced disease. They have not substituted surgery, chemotherapy or radiotherapy as first line treatments. Details of long-term side effects are unknown as patients taking them often do not have “long-term” outlooks. However, pushing boundaries and using therapies in metastatic settings has often led to changing practices in the adjuvant .

Conclusion

Health care professionals caring for patients with lung cancer strive constantly for improved health outcomes for their patients. Evidence based knowledge is changing practices and small molecule tki’s are very useful therapies for patients requiring more than chemotherapy or radiation. The literature supports this repeatedly.

Oral therapies present many advantages for the patient, primarily less hospital time and this is a very attractive option for patients who may have advanced disease. However, education regarding the importance of proper drug administration in the home is equally as important as for conventional chemotherapy.

Local pharmacists and public health nurses who support patients in the community may need educational updates on targeted therapies also. Improved communication pathways between hospital based healthcare teams and the community will help patients.

The side effect profile of these drugs is complex and they should not be dismissed as “only tablets”. Structured guidelines like the ones for skin toxicities from anti-EGFR will need constant developing as experience with the drugs grows. Increased use may reduce costs in time.

Overall, I believe that these therapies provide hope for patients. In my 15 years oncology experience, sharing news of developments in research is worthwhile. Patients above all are aiming, hoping and craving for the vision that;
‘Ireland will have a system of cancer control which will reduce our cancer incidence, morbidity and mortality rates”
Cancer Control Strategy 2006

Nuala is director of Hannon Oncology Education Ltd.
Email: nuala@hannononcologyeducation.ie

References

BMJ Group, (2010) British National Formulary 60 Tavistock Sq, London: Pharmaceutical Press.

Cancer Information and Support Network (2006) The Promise of Targeted therapy U.K

Department of Health and Children (2006) A Strategy for Cancer Control in Ireland:National Cancer Forum 2006 Dublin: Department of Health.

Irish Advisory Panel (2012) Management of Anti-Epidermal Growth factor Receptor (Anti-EGFR) Skin Toxicities Santry: Amgen Ireland Ltd.

International Society for Nurses in Cancer Care (2012) Nurse-led Small Molecule Targeted Therapy Patient Education Programme U.S.A

Katakami, N et al (2013) LUX-Lung 4: A Phase II Trial in patients with advanced non- small -cell lung cancer who progressed during prior treatment with erlotinib gefitinib or both. Journal of Clinical Oncology 3335-3341 published on line.

National Cancer Institute (2010) Gefitinib Improves Progression free Survival for Metastatic Lung Cancers with EGFR Mutations U.S.A.

Health service Executive (2012) Primary Care Re-Imbursement Service –Analysis of Claims 2012 Dublin: Health Service Executive

Shaw, A.T et al (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New England Journal of Medicine 20 2385-94.

Shtivelman, E. (2014) Asco 2014 lung cancer roundup My Cancer Commons (Electronic) (2pp) “Available”: cancercommons.org/2014/06 /11/asco-2014-lung-cancer-roundup/