Call for QOL Experiences With Targeted Therapies

Recently, we completed a review of psychological and quality of life data literature on patients receiving targeted therapies.  Very little is currently available on this topic.  The few studies that were available dealt with imatinib (or another TKI such as sorafenib), along with fatigue and/or adherence to long-term oral chemotherapy.¹ There are a few unique trials worth discussing. 

One trial examined targeted therapy use at the end of life and found that they were most likely to be given in younger patients and those patients with hematological malignancies.² Also, rash was explored and a series of studies found that although the cetuximab rash reduced QOL for patients, they were mostly willing to tolerate this side effect because their oncologist universally reassured them that the rash meant that the drug was working.^3,4  Similarly, good data exists for tamoxifen where QOL studies did not show a direct link to weight gain and decreased libido.⁵ In terms of counseling a patient on medication, it is wonderful to have this kind of information. 

It was perhaps not surprising to find that such data typically lagged behind FDA approval by 5 to 8 years.  Adherence to oral chemotherapy is much more dependent on patient factors and it is incumbent upon the prescriber to consider. 

Another socially related issue is cost, which is beginning to receiving considerable attention.  A study found that "financial toxicity" was reported in 42% of an insured cohort who described applying for copayment assistance (75%), reducing spending on food (46%), taking less than prescribed (20%), partially filling their prescription (19%), and avoiding filling prescriptions altogether (24%).⁶

We also found information about the communication gap that exists between doctor and patient regarding targeted therapies.  Patients do not understand "personalized medicine" to mean "biologically personalized."  It conjures up images of holistic care.  Although patients are generally inspired by the hope that these new medications bring, they may not care as much about the underlying biology and are still concerned with side effects and outcomes similar to their concerns with cytotoxic therapies. 

I received an email this morning from a friend whose family member was diagnosed with stage III melanoma; I immediately looked up the latest trial.  Does ipilimumab belong in the first-line setting yet?  I hate to tell my friend, but her uncle may require 1 year of treatment with interferon alpha.  I find myself writing: “Ipilimumab toxicities are not quite universal, mostly autoimmune in nature, although sometimes quite severe."  The hope is contagious.  I suppose it’s just human nature.  Although targeted therapies are increasingly better tolerated, many issues still remain unexplored. 

There is a balance between making medical decisions based on empiric evidence and patient factors or anecdotal physician experience--the "art" of medicine, so to speak.  With oncology, we generally make decisions based on evidence of overall survival, progression-free survival, and tolerability.  The first two are undebatable; however, the last has been negotiable, historically.  Thankfully, as noted above, some of the QOL issues may be mild or tolerable as long as the data supports that.  However, there is a complex array of decision-making and QOL issues with targeted therapies that have not been settled.  

Here are a few of those issues that I thought of with melanoma: 

• There may be a couple different choices when it comes to treatment, so shared-decision making for a patient with metastatic melanoma who has a BRAF V600E mutation is important.  They can either start therapy with vemurafenib, which has a high response rate (RR) of 48%, but shorter duration of response, or start with ipilimumab, which has a much longer duration of response (19.3 months), but a very modest RR of 15.2%.^7,8  How do you decide which comes first? What is the best way to begin a conversation with a patient to come up with the decision when there’s not enough survival evidence either way?  
• What is the psychological effect of a newly developing cutaneous squamous cell carcinoma while a patient is on the BRAF inhibitor vemurafenib?  
• How does taking a life-prolonging oral chemotherapy pill affect patients psychologically vs accepting physician-controlled infusion therapy?  Is there temptation for the patient not to take the pill when feeling well?

We would be very interested to hear of other QOL, financial, or communication issues that have been encountered in practice with regard to targeted therapies which may not have received attention in the literature. 

Would anyone be so kind to share their experiences? 

Disclosures:

Daniel McFarland is a clinical fellow in hematology and medical oncology at Mount Sinai Medical Center in New York City and a member of the American Psychosocial Oncology Society. He is dually trained in internal medicine and psychiatry. As part of the American Psychosocial Oncology Society, Dr. McFarland is currently collaborating with Dr. Jimmie Holland at Memorial Sloan Kettering Cancer Center in an effort to bring psychosocial issues to the attention of oncologists as they treat patients in the new era of personalized medicine. The views expressed are his own.

References:

• Efficace F, Rosti G, Cottone F, et al.  Profiling chronic myeloid leukemia patients reporting intentional and unintentional non-adherence to lifelong therapy with tyrosine kinase inhibitors.  Leuk Res.  2014; 38(3): 294-8.
• Hui D, Karuturi MS, Tanco KC, et al.  Targeted agent use in cancer patients at the end of life.  J Pain Symptom Manage.  2013; 46(1): 1-8.
• Unger K, Niehammer U, Hahn A, et al. Treatment of metastatic colorectal cancer with cetuximab:  influence on the quality of life.  Z Gastroenterol.  2013; 51(8):  733-9. 
• Romito F, Giuliani F, Cormio C, et al. Psychological effects of cetuximab-induced cutaneous rash in advanced colorectal cancer patients.  Support Care Cancer.  2010; 18(3):  329-34. 
• Zafar SY, Peppercorn JM, Schrag D, et al.  The financial toxicity of cancer treatment:  a pilot study assessing out-of pocket expenses and the insured cancer patient’s experience.  Oncologist.  2013; 18(4):  381-90. 
• Ganz PA.  Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life.  Journal of the National Cancer Institute Monographs.  2001; 30:  130-134.
• Chapman PB, Hauschild A, Robert C, et al.  Updated overall survival results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib with DTIC in previously untreated patients with BRAF V600E mutated melanoma.  J Clin Oncol.  2012; 30 (suppl; abstr 8502). 
• Robert C, Thomas L, Bondarenko I, et al.  Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.  N Engl J Med.  2011; 364:  2517-2526.