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HOPA Publications Committee

Bonnie Labdi, PharmD RPh, Chair

Ashley Glode, PharmD BCOP, Vice Chair

David DeRemer, PharmD BCOP, Board Liaison

Brandi Anders, PharmD BCOP Megan Bodge, PharmD

Megan Brafford, PharmD BCOP

Courtney Cavalieri, PharmD BCOP Morgan Culver, PharmD BCOP

Morgan E. Culver, PharmD BCOP

Erika Gallagher, PharmD BCOP

Lisa Lohr, PharmD BSPharm BCOP BCPS

Jennifer Kwon, PharmD BCOP

Trevor McKibbin, PharmD MS BCOP

Christan Thomas, PharmD BCOP

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Board Update: New Beginnings at HOPA

about board bio scott soefje
Scott Soefje, PharmD MBA BCOP FCCP
HOPA President

HOPA starts a major new beginning this year as a provider of recertification education for the Board Certified Oncology Pharmacy (BCOP) program. While HOPA has been providing BCOP programming at our Annual Meeting for several years, that programming was in collaboration with the American College of Clinical Pharmacy, and was offered as a convenience to our members. We did organize and develop the programming and gain valuable insight into what the oncology pharmacist wanted, but we were not the official providers. This year we move into official-provider status and I want to spend time out- lining what this means for oncology pharmacists.

To understand how HOPA became a provider, you need to know a little history. The 2015 response to a request for proposal (RFP) was not the first time that HOPA had planned to respond to the Board of Pharmaceutical Specialties (BPS) call for new programs. Several years ago, the HOPA board authorized a group to develop a proposal in anticipation of BPS putting out an RFP. This proposal was never submitted, because BPS put a freeze on new program development while it conducted a self-study to determine the effectiveness of board certification for pharmacists. HOPA participated in BPS task forces to provide feedback on the benefits and needs of the certification process. In 2015, the call went out again for providers for BPS programming. HOPA submitted to become a BCOP provider and heard from BPS in mid June 2015 that we had been accepted as one of two providers.

Then the real work started. Our proposal was that we would start the offering in January 2016. We had to develop the infrastructure, the committees, the process, and, finally, the content to offer our first webinar by February 2016. A daunting task for any organization, but I can say, HOPA pulled it off exceptionally well. We also listened to our membership and designed a BCOP recertification program that meets the current needs of the oncology pharmacist. We are offering 38 hours per year of qualified recertification education credits. These are broken down into four different offerings. Let us take a closer look at each offering.

First are the Emerging Issues in Oncology Pharmacy webinars. Five webinars, 1 hour each, will recap the best of and most important information needed by oncology pharmacists from five of the top oncology meetings including ASH, San Antonio Breast Cancer Symposium, ASCO, ASPHO, and ASBMT Tandem Meetings. These webinars will be live and enduring allowing you to view them on your own schedule. We then have the programming at the Annual Meeting in Atlanta. This programming will be 8 hours and will be repeated at the Practice Management Symposium in Chicago and eventually made an enduring program online. We listened to members and no longer do you have to get all 8 hours at one venue. You can mix and match as it suits your needs.

New this year, HOPA is beginning our third live annual program with the Oncology Pharmacy Updates Course. This course will focus on BCOP-level content that, over a 3-year period, will cover all of the core elements required for BCOP recertification. This is not an entry level course. We heard from members that there was a need to “ramp up the content” to reflect the level of practice a BCOP pharmacist provides. Held in July every year, this course provides that higher level of learning and will be a live session offering 10 hours of credit. This content will ultimately be put online as well. Lastly is the Self-Study Online Program. This 15-hour pro- gram is a mix of case-based learning and literature review focusing on new advances that will affect oncology pharmacy practice. This program will be entirely online and will allow self-paced learning.

This programming provides an exciting new start to the BCOP offerings for HOPA. We feel we have developed a diverse set of pro- grams that will meet the educational needs of our members, but we still want your feedback. As you can see, many of the ideas and programming are based directly on feedback from the members, so it is extremely important that you continue to provide that feedback.

Our Annual Meeting offers another opportunity for beginnings— our first off-site preconference symposium. Emory University has opened up its campus to offer the preconference “Phase I Clinical Trials: Establishing a Culture and Infrastructure for Conducting Drug Development Studies.” We have other preconference offerings in bone marrow transplantation and immuno-oncology, so we hope there is something for everyone.

Every year we struggle to bring in a keynote speaker that excites, interests, and provides relevant information to the oncology pharmacist. I hinted in an earlier address that we would have a special speaker, and I am very pleased that this year we were able to get one of the most popular requests on the member feedback to be our speaker. We are pleased to welcome Siddhartha Mukherjee, MD PhD, a leading cancer physician and researcher, as our John G. Kuhn Keynote lecturer. You may know Dr. Mukherjee as the author of The Laws of Medicine and The Emperor of All Maladies: A Biography of Cancer, which won the Pulitzer Prize for general nonfiction in 2011. The latter book was converted into a 6-hour Public Broad- casting Service (PBS) offering by Ken Burns and Barak Goodman, which aired on PBS in March 2015. We look forward to Dr. Mukherjee’s insights and views on cancer care.

While 2015 was an exceptional year for HOPA—our accomplishments are numerous, our external connections grew, and we see a strong and healthy organization—I can only imagine what 2016 will bring us. We are definitely off to a great start. New beginnings bring great new opportunities. So make sure you take advantage of the BCOP offerings and I hope to see every one of you at the Annual Meeting in Atlanta.

Happy New Year!


 

Cost of Cancer Care: Evaluating Financial Toxicity

Courtney C. Cavalieri, PharmD BCOP
Clinical Hematology/Oncology Pharmacist
Huntsman Cancer Institute at the University of Utah Salt Lake City, UT


It’s no secret: the cost of cancer care is rising. Over the last few years, a plethora of reports have surfaced examining the seemingly outrageous cost of new cancer therapies in relation to their effectiveness. A 2010 analysis estimated the national cost of cancer care will increase from $125 billion in 2010 to $158 billion in 2020.1   Why are expenses increasing? Reported contributing factors include an aging population with an increasing prevalence of cancer, the advent of new drugs and new techniques in radiation therapy and surgery, the increasing use of more expensive diagnostic techniques, and the availability of health care to a larger population.2,3

An oft-cited cost from “bench to bedside” for anticancer medications is $1 billion, which is too often used as justification for the high price of drugs.4 Unfortunately, the principle of “just price or fair price” does not apply to cancer medications, which are priced by their own market rules and do not follow the idiom of being priced at “what the market will bear.”5 The hope is that the price reflects the benefits and value of the treatment, as well as the cost of research and development. However, this not always the case. National headlines were made in 2012 when Bach and colleagues submitted an editorial in The New York Times that drew attention to the price of zivaflibercept, which was twice that of bevacizumab despite producing similar efficacy results in patients with metastatic colorectal cancer.6 Imatinib, a tyrosine kinase inhibitor (TKI), cost $30,000 per year in 2001 when it was approved for chronic myeloid leukemia, and had inflated to $80,000–$92,000 in 2012. This was even though newer TKIs have since been approved in imatinib-resistant disease and have even shown improvements in early surrogate end points when compared head-to-head with imatinib.4 So what actually determines the cost of a drug? The lead contributor may be reimbursement. The majority of cancer medications are dispensed within the confines of a physician’s office or ambulatory infusion clinic and are therefore covered by the patient’s medical benefits (versus pharmacy benefits). Manufacturers may competitively increase the prices of drugs to provide the dispensing physician a larger margin of financial benefit while ignoring the harmful effect on the patient’s financial situation.7Throughout the continuum of cancer treatment, patients undergo various procedures and systemic therapies. Numerous risks and adverse events of these treatments are well documented, but all these interventions share one toxicity in common that has gained a new official name: “financial toxicity.” Doctors Yousuf Zafar and Amy Abernethy highlighted the life-altering effect of financial toxicity in a two-part series published in the journal Oncology describing one patient and her family.3,8 The 67-year-old breast cancer patient, nicknamed “Janet,” admitted to her physician that her family doesnt travel anymore, nor do they do anything” due to her “$100,000 illness.” “It sucks,” she admitted, “but what are you going to do?” 3 Patients who are uninsured may trigger concerns about cost at the forefront of their care. However, with increasing medical expenses across the board, even patients with adequate insurance are feeling the sting of medical debt. Third-party payers have shifted costs to patients, increasing their out-of-pocket costs. Not only have we seen more high-deductible plans, but insurance premiums have also had a huge impact on patients’ bank accounts. Between 1999 and 2011, premiums in- creased 170%, while worker earnings increased only 50%.3

Cancer patients have an especially daunting problem. Nationally, 9.7% of adults with chronic conditions report a high objective financial burden. This is compared to 13% of cancer patients in the same age range.3 Cancer care is one of the fastest growing components of U.S. healthcare costs, and patients are feeling the growing pains. Patients who experience high out- of-pocket costs report reduced spending on food and clothing, poor adherence to costly medications, and avoidance of recommended procedures and appointments.2 It has unfortunately been accepted as “the norm” by many patients, cancelling vacations, using life savings, and working overtime just to pay for their treatments.3 Out of a surveyed group of insured patients applying for financial assistance, 68% reported they cut back on leisure activities, 46% reduced spending on food and clothes, 46% used their savings, and 17% sold possessions or property just to pay for cancer-related costs. 9

So, what can be done about this? The first step has already been taken. Transitioning cancer cost from the elephant in the room to a public conversation has already had an effect. Within a week of Bach and colleagues’ New York Times editorial, the manufacturer of zivaflibercept reduced the price by half.4 Last year, 60 Minutes aired a special on the cost of cancer drugs in which the term “financial toxicity” was broadcast to the masses. In the special, Leonard Saltz, MD, blamed pharmaceutical companies for taking advantage of people’s fear and anxiety about their cancer diagnosis. Hagop Kantarjian, MD, very bluntly admitted, “The only drug that works is a drug that the patient can afford.” 10  Dr. Saltz has continued his quest to draw attention to the unsustainable costs of cancer care. This year, in the plenary session at the American Society of Clinical Oncology (ASCO) annual meeting, he highlighted concerns with the new immunotherapy drugs reporting annual costs potentially reaching $1 million per patient.11

There are a variety of factors that allow this extraordinary cost of medications. One of the biggest barriers is the prohibition of the Centers for Medicare and Medicaid Services (CMS) to negotiate the price of drugs coming to market, which Dr. Saltz addressed as a start to the high-cost solution. Another barrier that needs to be ameliorated is the allowance of pharmaceutical companies to pay fees to delay the introduction of competing generics.12 Dr. Saltz also reinforced that the U.S. Food and Drug Administration (FDA) should be allowed to consider price in the approval process as other nations do.11  The United Kingdom’s National Institute for Health and Care Excellence has a formalized process involving clinical and econometric analyses to determine the value of a new therapeutic option. Canada, Australia, France, and Germany all have similar processes that consider efficacy, toxicity, and cost in the context of disease prevalence, medical need, and prevailing alternatives. Despite the United States far exceeding these other countries in healthcare spending, improvements in health outcomes have failed to match that growth. Adults in the United States, more than any of these other countries, had access issues to health care because of treatment cost.13  Patients in the United States are paying two-three times more for the same drug than patients in Canada, Australia, and other European countries. 10 We are aware of the overarching issues that need to be addressed, but until they are, we have to focus on each individual patient. The question that needs to be answered first is: When is the appropriate time, if any, to talk about cost with patients? Cancer patients may be more sensitive to a discussion regarding cost in relation to value. Patients may be hesitant to broach the subject of cost on their own due to embarrassment about financial distress or inflated beliefs in benefit from therapy.8 If patients are not coming forward on their own, is there a way to identify patients who may be more susceptible to financial toxicity? Singling out patients by age, ethnicity, education level, income, or employment status will not necessarily identify all patients at risk. Insured patients may be falling under the radar of who we typically think will suffer from financial toxicity. Stump and colleagues reported almost half of insured cancer patients they surveyed report concerns about costs, and 22.3% report personal and family sacrifices just to pay for their cancer care.14   One recommendation is to monitor for financial toxicity the same way we would for any other toxicity from treatment: at each visit, patients would be screened for adverse events as they normally are, but with the inclusion of financial distress or concerns.8

The COST (comprehensive score for financial toxicity) measure was developed for exactly this purpose. The 11-item questionnaire assesses patients’ concerns about their current financial situation, future financial issues, and direct and indirect financial barriers. The final COST measure score can be used to assess the severity of an individual patient’s financial toxicity.15

ASCO formed the Task Force on the Cost of Cancer Care in 2007 to address how to help providers deliver the highest-quality care with- out compromising for cost. In 2013, the ASCO Board of Directors charged the Task Force to develop a system to compare relative clinical benefit, toxicity, and the cost of treatment in the medical oncology setting. This framework was published in June 2015. 2 This framework is guided by the core principles of the physician-patient relationship to ensure informed decision-making and to encourage the provider to be a good steward of healthcare resources. The task force defined value in cancer care by emphasizing clinical benefit (efficacy), toxicity (safety), and cost (efficiency). Value was then assessed using quality-adjusted life-years and incremental cost-effectiveness ratios. Two frameworks were then developed: one for advanced cancer and another for potentially curative cancer. In the advanced disease framework, clinical benefit is given a categorical score based on the fractional improvement in median overall survival (OS) when com- paring a new therapy with the standard-of-care therapy. If OS was not reported or assessed, progression-free survival (PFS) is used. If neither OS nor PFS is available, overall response rate (ORR) is used. In the curative framework, the hazard ratio (HR) between OS of the new and standard of care regimens is used. If the HR for OS is not available, then the HR for disease-free survival (DFS) is used. OS, PFS/ DFS, and ORR are all weighted differently, with OS being weighted the highest as it represents the most important component of the value assessment. In both frameworks, toxicity is given a categorical score (-20 to +20) based on the relative toxicity of the new therapy versus the standard of care. Bonus points can also be awarded for statistically significant improvement of cancer-related symptoms or improvement in treatment-free interval. Once the points are combined, it results in the net health benefit (NHB) score. Two types of cost estimates are included: drug acquisition cost and patient cost. The NHB is then compared to cost to facilitate the assessment of value. 2

There are weaknesses with these frameworks. First, their comparisons are extremely narrow in scope. They can only compare therapies within the context of the study and not to other regimens. Second, the information provided by these frameworks must be able to be presented in an understandable way to patients to ensure their participation in treatment-related decisions. 2 As the task force continues to strengthen these frameworks for general use, they are still useful conversation-starters about the value of care.

Pharmacists are primed to help patients handle financial toxicity—not only on an individual basis, but also as a whole organization. Kantarjian and colleagues recommended that professional societies representing cancer specialists should reduce the hype around new antineoplastics that have no major effects on patient outcomes. 5 Pharmacists can provide information through pharmacy technicians specifically trained to handle prior authorization requests and well-versed in the various patient assistance programs. Pharmacy technicians specially dedicated to these programs can greatly reduce the stress on patients who may not be familiar with the particular avenues available. When a patient is set to start a new, possibly cost-prohibitive treatment, the pharmacy technician would be immediately involved to search out and summarize the financial assistance programs for which the patient may be eligible.

Pharmacists can also be more involved with economic analyses re- search. This is especially impactful to show how cost affects patient adherence, and therefore outcomes. If the discussion of cost is brought to the forefront of prescribing, pharmacists and prescribers can have open conversations about what is in the patient’s best inter- est. This may not always be appropriate when considering chemotherapy. However, when discussing supportive care options, there may be a variety of medications to choose from that are similar in effectiveness yet vastly different in cost.

The evaluation of cost in relation to benefit is not a new concept. Aristotle was the first to examine cost in relation to worth in the Nicomachean Ethics. More than 2,000 years later, we are still striving for Aristotle’s justum pretium: the just price. Determining the just price for cancer care is a conflict the oncology community is not quite prepared to handle. However, the first steps towards curing financial toxicity are being taken with increased conversation and development of cost- conscious practice guidelines.

 

References

1.     Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst2011;103:117-128.

2.     Schnipper LE, Davidson NE, Wollins DS, et al. American Society of Clinical Oncology Statement: A conceptual framework to assess the value of cancer treatment options. J Clin Oncol.2015;33(23):2563-2577.

3.      Zafar SY, Abernathy AP. Financial Toxicity, part I: A new name for a growing problem. Oncology. (Williston Park). 2013;27(2):80-81.

4.     Kantarjian H, Fojo T, Mathisen M, et al. Cancer drugs in the United States: Justum Pretium—The just price. J Clin Oncol.

2013;31:3600-3604.

5.     Kantarjian H, Steensma D, Sanjuan JR, et al. High cancer drug prices in the United States: Reasons and proposed solutions.

J Oncol Pract. 2014;10:e208-211.

6.     Bach P, Saltz L, Wittes R. In cancer care, cost matters. New York Times, October 15, 2012:A25.

7.      Danzon PM, Taylor E. Drug pricing and value in oncology. The Oncologist. 2010;15 (Suppl) 1:24-31.

8.     Zafar SY, Abernethy AP. Financial Toxicity, part II: How can we help with the burden of treatment-related costs? Oncology.

2013;27(4):253-254.

9.      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. The Oncologist. 2013;18:381-390.

10.   The cost of cancer drugs. "60 Minutes." CBS television. October 5, 2014.

11.    Saltz L. Perspectives on value. Presented at: Annual Meeting of the American Society of Clinical Oncology; May 31, 2015; Chicago, IL..

12.   Pfister DG. Cost of cancer care: Oncologists need to be part of the solution. J Clin Oncol. 2013;31:3487-3489.

13.    Commonwealth Fund Commission on a high performance health system: Why not the best? Results from the National Scorecard on US Health System Performance. 2011. Available at: http:// www.commonwealthfund.org/~/media/files/publications/fund- report/2011/oct/1500_wntb_natl_scorecard_2011_web_v2.pdf. Accessed July 2015.

14.   Stump TK, Eghan N, Egleston BL, et al. Cost concerns of patients with cancer. J Oncol Pract. 2013;9:251-257.

15.   de Souza JA, Yap BJ, Hlubocky FJ, et al. The development of a financial toxicity patient-reported outcome in cancer. The COST measure. Cancer. 2014;120:3245-3253.



Reliability of PD-L1 as a Predictive Biomarker in NSCLC

Courtney C. Cavalieri, PharmD BCOP
Clinical Hematology/Oncology Pharmacist
Huntsman Cancer Institute at the University of Utah Salt Lake City, UT


Even through numerous developments in treatment, lung cancer re- mains the leading cause of cancer death in the United States.1 Many avenues have been attempted to prolong overall survival of this dis- ease. The most recent has been immunotherapy, specifically immune-checkpoint inhibitors targeted at the programmed death 1 (PD-1) receptor. Nivolumab and pembrolizumab are the two immunotherapies currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of progressive non-small cell lung cancer (NSCLC). Although these agents may be similar in target, their respective journeys to approval revealed we have much to learn about the impact of these therapies.

Nivolumab was approved first for squamous NSCLC in March 2015 based on the CheckMate-017 phase 3 trial. This compared nivolumab to docetaxel in patients with advanced squamous NSCLC who had progressed on or after receiving a platinum-based chemotherapy regimen. Nivolumab provided an improved median overall survival (9.2 versus 6.0 months), response rate (20% versus 9%), and progression- free survival (3.5 versus 2.8 months) over docetaxel. Nivolumab also produced fewer grade 3 or 4 adverse events at 7%, compared with the 55% in the docetaxel group.2 In October 2015, the FDA extended the approval to non-squamous NSCLC based on the results of the CheckMate-057 phase 3 trial. CheckMate-057 compared nivolumab to docetaxel in patients with non-squamous NSCLC after progression during or after platinum-based chemotherapy. Again, nivolumab proved superior to docetaxel, with improved overall survival (12.2 versus 9.4 months) and response rates (19% versus 12%). The data for median progression-free survival did not actually favor nivolumab (2.3 versus 4.2 months). However, at 1 year, a higher percentage of patients treated with nivolumab were alive than those treated with docetaxel (19% versus 8%), representing a delay in response to therapy known to occur with immunotherapy. Nivolumab still proved to be better tolerated, with only 10% reporting grade 3 or 4 adverse events compared to the 54% in the docetaxel group.3

Pembrolizumab was approved for NSCLC in October 2015 based on the data from the phase I KEYNOTE-001 trial. The objectives of KEYNOTE-001 were to evaluate the side effects, safety, and anti- tumor activity of pembrolizumab in NSCLC patients, as well as de- fine and validate a tumor PD-L1 expression level associated with an increased likelihood of benefit from pembrolizumab. Pembrolizum- ab was given at a dose of 2 mg/ kg every 3 weeks, 10 mg/ kg every 3 weeks, or 10 mg/ kg every 2 weeks. PD-L1 positivity was determined by an immunohistochemical (IHC) assay and defined as at least 1% of cells showing membranous staining (proportion score). The investigators determined ≥50% proportion score as the cutoff for validation of PD-L1 as a predictive biomarker. The most common adverse events reported were fatigue, pruritus, and decreased appetite. The overall response rate was 19.4% across untreated and previously treated patients. Median overall survival was 12 months and progression-free survival was 3.7 months. No differences in response rates or toxicities were seen between the varying doses and schedules; therefore, the investigators recommend the 2 mg/ kg every 3 week schedule. Patients with ≥50% proportion score per the validation assay had longer progression-free survival than patients with 1% to 49% or <1% proportion scores (6.3 versus 4.1 versus 4.0 months, respectively) and longer over- all survival (not reached versus 10.6 versus 10.4 months, respectively). The FDA approval for pembrolizumab in NSCLC dictates patients must test positive for PD-L1 with the companion diagnostic assay.4

KEYNOTE-001 suggests that PD-L1 expression (at ≥50% proportion score) may represent a predictive biomarker for the treatment of NSCLC with pembrolizumab.4 However, the CheckMate trials provide conflicting reports on whether PD-L1 expression is a valid biomarker. CheckMate-017 defined samples as PD-L1 positive at pre- defined levels of 1%, 5%, and 10% and found no difference in predictive benefit of nivolumab activity.2 CheckMate-057 used the same IHC assay as CheckMate-017 and the same predefined positivity levels. At the interim analysis, an association between PD-L1 expression and clinical outcome was described. Expression above the predefined levels all correlated with better survival outcomes than docetaxel; however, in patients whose tumors had negative expression, the survival outcomes were similar to docetaxel. The authors concluded that because the safety profile of nivolumab out-performed docetaxel, nivolumab should still be considered an option regardless of PD-L1 expression.3

The question these three trials raise is whether PD-L1 is a reliable biomarker for predictive response to immunotherapy, particularly in NSCLC.

In the CheckMate trials assessing nivolumab in NSCLC, PD-L1 expression was relatively consistent at 83% in CheckMate-017 and 78% in CheckMate-057. 2,3 In KEYNOTE-001, 23.2% of patients had a pro- portion score of at least 50% and 37.6% had 1%-49%.4 Other trials exploring immunotherapies in NSCLC describe positivity for PD-L1 expression ranging from 21% to 95%. PD-L1 expression varies with disease state, with reports for melanoma patients ranging from 38% to 100% and reports for renal cell carcinoma ranging from 14% to 54%, depending on which site of disease was tested (primary versus metas- tasis).5 The wide range of positivity could be explained by each dis- ease state’s heterogeneity; however, trials have not been consistent in which IHC assay has been used to determine PD-L1 positive expression.

As of this time, there is no standard IHC assay used to calculate expression of PD-L1, nor is there a standard definition of “positive” expression. There are about two dozen anti-human PD-L1 antibodies currently being used in IHC assays, including 28-8, 5H1, MIH1, and 20C3. In addition, manufacturers of PD-1 and PD-L1 inhibitors con- currently develop their own proprietary companion test when seeking FDA approval. All these different assays complicate the ability to possibly standardize PD-L1 positive quantification. Cutoff points for positive PD-L1 expression range from >1% to >50%, which would explain the incidence of patients who are considered PD-L1 “positive” yet do not respond to immunotherapy as expected, and conversely, the patients considered PD-L1 “negative” who do respond to therapy.6 Al- though PD-L1 expression may not be the best biomarker to include or exclude patients to receive immunotherapy, levels of expression could possibly be used to guide which regimens of immunotherapy may benefit the patient the most. It is clear that patients who have higher rates of PD-L1 expression do respond better to single-agent immuno- therapy, and patients who have lower or negative rates of PD-L1 expression may be better suited to receive combination immunotherapy. Differing levels of expression could also be used to stratify patients in clinical trials exploring new combinations of immunotherapy.7

Although PD-L1 presents as a tempting predictive biomarker for immunotherapy in NSCLC, there are a few barriers before relying on PD-L1 as a definitive biomarker to choose which patients should or should not receive immunotherapy. Standardization must occur across assays as to which anti-PD-L1 antibody is used for expression description. The cut-offs for what constitute positivity must also be ad- dressed, and may be dependent on tumor type, biopsy site, and assay used to determine positivity. As immunotherapy becomes an option for more patients with oncologic diseases, these issues will hopefully be addressed through future clinical trials.

References

1. National Comprehensive Cancer Network Clinical Practice  Guidelines in Oncology: Non-Small Cell Lung Cancer. V1.2016. 

2. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer.  N Engl J Med. 2015;373:123–135.

3. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639. 

4. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med. 2015;372:2018–2028.

5. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847–856.

6. Teixido C, Karachaliou N, Gonzalez-Cao M, et al. Assays for predicting and monitoring responses to lung cancer immunotherapy. Cancer Biol Med. 2015;12:87–95.

7. Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology. (Williston Park). 2014;28 (Suppl) 3:39–48.


Highlights from the JADPRO Live at APSHO 2015 Conference

Megan  Brafford May, PharmD BCOP
Clinical Oncology Pharmacy Specialist Baptist Health Lexington
Lexington, KY


The third annual Journal of the Advanced Practitioner in Oncology (JADPRO) Live conference was held in Phoenix, AZ, on November 5–8, 2015. This conference was held in conjunction with the second annual Advanced Practitioner Society for Hematology and Oncology (APSHO) meeting. The focused theme of this year’s meeting was “Collaborate, Learn, Care, and Lead” and concentrated on advanced practitioners and physicians coming together to discuss current treatment options and advances in the care of cancer patients. The first day of the conference consisted of multiple workshop options: grant writing advice, an immunotherapy primer, everyday applications to be used as tools and technology, primary care considerations for the patient with cancer, and a hands-on skills workshop reviewing bone marrow aspiration, lumbar puncture, Ommaya reservoir placement, punch biopsy, and suturing.

The remaining three days consisted of more than 20 educational sessions comprising didactic, interactive, patient case-based and evidence-based content targeted to advanced practitioners in oncology, including nurse practitioners, physician assistants, clinical nurse specialists, other advanced-degree nurses, hematology/oncology nurses, pharmacists, and physicians. Each presentation reviewed best practices involving a multidisciplinary setting. One of the unique characteristics of the JADPRO Live conference is that the majority of presentations included at least two speakers with different roles from the multidisciplinary team.

One of the panel discussions on “Revolution at the Corner Drugstore” addressed the importance of the collaborative practice team in order to manage multiple issues regarding the increased use of oral chemotherapies such as drug payment assistance, monitoring for drug adherence, dosing issues, proper patient education, and managing toxicities. The panel stated, “with approximately 800 oncology drugs in the pipeline and 40% of these being oral medications and 80% of those being first-in-class medications, the need for increased aware- ness of oral chemotherapies is imperative.” Each year, approximately $100 billion to $300 billion dollars are spent on health care due to non- adherence. The panel discussed the benefit of providing calendars to patients on oral agents to increase adherence. Matthew Farber (senior director of oncology for Walgreens) noted that pharmacists can and should play a larger role in assisting patients with reimbursement and other critical issues related to oral therapy. Other major topics discussed included herbals and supplements and their interaction with oral chemotherapies, as well as the need for accurate medication reconciliation.

An additional program directly related to pharmacy topics included “Review of Newly Approved Oncologic Therapies.” This was a great review of pharmacology and indications of every new oncology/ hematology drug approved in late 2014 and the first half of 2015. Recommendations for monitoring and management of treatment-related toxicities were also addressed. Lastly, this presentation emphasized the impact of each of these medications on advanced practitioners and how to utilize each medication in clinical practice.

Another highlight was the keynote presentation by Laura Adams, titled “There’s a Patient on the Care Team: The New Design for Health and Healing.” The resonating statement throughout the presentation was the confirmation that what we do as healthcare professionals matters and that we touch our patients’ lives with everything we do. Laura shared her concerns regarding the lack of patient record sharing throughout our entire healthcare system and addressed the many issues this creates for our patients. She also shared her personal story regarding coping with and surviving breast cancer. Utilizing her personal experiences, she is educating providers to ensure the patient is a part of each medical team. Collaboration may be the most important survival strategy for every organization and the patient. She left the audience with the quote “We can only connect the dots we collect.”
JADPRO Live at APSHO 2015 gave practitioners the opportunity to network with providers from various specialties and work together to better serve our patients. More information about joining APSHO and attending JADPRO Live can be found at the website www.apsho. org. Save the date for the 2016 meeting at the Gaylord National Hotel in Washington, DC, November 3–6, 2016.


Survey of Interest in Future HOPA Standards/ White Papers: Summary of Results

Raj Duggal, PharmD BCOP
Oncology Clinical Pharmacist
IU Health-IU Simon Cancer Center
Indianapolis, IN

In February 2015, a survey was submitted to the HOPA membership to identify topics for future standards or white papers. This survey was prepared and reviewed by members of the Standards Committee.

The survey asked participants about practice setting, time in clinical practice, and their interest in a list of topics for future standard or white paper development. Survey participants also had the opportunity to identify additional topics of interest not listed in the survey.

Results: There were a total of 225 responses to this survey, capturing 10% of HOPA’s membership. The majority of respondents (65%) classified themselves as clinical oncology pharmacists; 31% had been in practice for less than 5 years and 23% for 5–10 years. Approximately 29% of survey participants listed their primary practice setting as hospital inpatient, while an additional 27% listed it as an ambulatory infusion center.

Given a list of potential topics for standard or white paper development, survey participants rated development of chemotherapy template standards/decision-making tools and dose rounding of chemotherapy/targeted therapy (average score of 4.08 and 3.89 out of 5, respectively). When asked to rate the two top priority projects for potential standard or white paper development, development of chemo- therapy template standards and decision-making tools, as well as dose rounding of chemotherapy/ targeted therapy, scored highest (47% and 38%, respectively). Additional lower-priority topics were considered, including pharmacist involvement in personalized medicine (36%), clinically relevant drug interactions between chemotherapy and complementary and alternative medicine (29%), oncology residency training clinical experiences (16%), drug triage in shortage situations (17%), pharmacy involvement in survivorship programs (13%), and fertility preservation and the involvement of pharmacists (3%).

When asked to provide additional potential topics, there were 31 suggestions that could be further categorized: oral chemotherapy (six responses), chemotherapy dosing (five responses), training/education (seven responses), administrative (six responses), and miscellaneous suggestions (seven responses). Requested topics included additional published guidance for dosing chemotherapy in special populations (e.g., obesity, organ dysfunction, age), benchmarking data for justification of additional pharmacist positions, and pharmacist involvement/ training in outpatient oral chemotherapy management.

Conclusions: This survey indicated that HOPA membership would prioritize standards or white paper creation for dose rounding of chemotherapy/targeted therapy and development of chemotherapy template standards and decision-making tools. After further review of currently available publications and standards, the Standards Committee and the HOPA Board of Directors recommended pursuing a white paper on dose rounding of chemotherapy and targeted agents since there is minimal published guidance. This paper would offer the greatest impact for the HOPA membership. The Standards Commit- tee will be meeting to further discuss this project.

Available resources for chemotherapy template standard and deci- sion-making tools include the National Comprehensive Cancer Net- work (www.nccn.org) with disease-specific order set templates for purchase, the American Society of Clinical Oncology (www.asco.org) with staging guidelines for specific cancers, and the Institute for Safe Medication Practices (www.ismp.org) with guidelines for standard order sets.

We thank the membership for your responses to this survey, as well as the individuals who developed, reviewed, and summarized the survey.

 


Recalls and Safety Alerts from the FDA

Jennifer Kwon, PharmD BCOPJennifer Kwon, PharmD BCOP
Hematology/Oncology Clinical Pharmacy Specialist
VA Medical Center
West Palm Beach, FL



 

RECALLS

Fluorouracil Injection (Adrucil)
Teva Parenteral Medicines issued a voluntary recall of six lots of fluorouracil injection (5 g/100 mL) because of the potential presence of silicone rubber pieces from a filter diaphragm and fluorouracil crystals. There have been no adverse events reported. For a full list of recalled products, visit, http://www.fda.gov/ Safety/ Recalls/ucm456093.htm.

Gemcitabine and Methotrexate
Mylan has issued a voluntary recall of select lots of injectable products, including gemcitabine and methotrexate, because of the presence of visible particles observed during a routine quality test. Lots of gemcitabine for injection were distributed in the United States. between January 8, 2014, and February 10, 2015. Methotrexate lots were distributed in the United States between December 8, 2014, and December 19, 2014. There have been no adverse events reported related to this recall. http://www.fda.gov/ Safety/ Recalls/ucm450140.htm

Moses Lake Professional Pharmacy Recall in Washington
Moses Lake Professional Pharmacy of Moses Lake, WA, voluntarily recalled certain unexpired human and veterinary sterile compounded drugs. This recall was a result of the lack of sterility assurance. These products were made from July 21, 2014, through July 21, 2015, and dispensed to patients or distributed to physicians in Arizona, Idaho, Florida, Oregon, Texas, and Washington. There have been no adverse events reported from the recalled products. For a complete listing of affected drugs, visit: http://www.fda.gov/ Safety/ Recalls/ucm455925.htm

 

SAFETY ALERTS

Anagrelide (Agrylin)
The clinical trial subsection under the adverse reactions section has been edited to list other less frequent adverse reactions (<1%) in both cardiac disorders (ventricular tachycardia, supraventricular tachycardia) and nervous system disorders (hypothesia). http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm175918. htm

Brentuximab (Adcetris)
Due to reports of fatal outcomes related to respiratory issues with brentuximab use, updates have been made in the warning and precautions section along with the adverse reactions section to address pulmonary toxicity. Pneumonitis, interstitial lung disease, and acute respiratory distress syndrome can occur and patients receiving brentuximab should be closely monitored for signs and symptoms of pulmonary toxicity. The medication should be held in the event of new or worsening pulmonary symptoms. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm426241. htm

Cabazitaxel (Jevtana)
Cabazitaxel is now contraindicated for use in patients with severe he- patic impairment (total bilirubin >3 ULN). Recommendations for use in patients with mild and moderate hepatic impairment have been added to the warning and precautions section of the prescribing infor- mation. Dose reductions should be made in the setting of mild (total bilirubin > 1 to ≤ 1.5 x ULN or AST > 1.5 x ULN) and moderate (total bilirubin > 1.5 to ≤ 3.0 x ULN and any AST) hepatic impairment. The updated warnings and precautions section includes bone marrow sup- pression, specifically neutropenia and its clinical consequences. Blood counts should be monitored carefully to determine if dose modifi- cations or G-CSF is needed. Patients with high-risk clinical features should be considered to receive prophylaxis with G-CSF. The use of cabazitaxel should also be used with caution in patients with hemoglo- bin <10 g/dL. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm392358.htm

Ceritinib (Zykadia)
Updates have been made to the warnings and precautions section of the package insert for ceritinib. The update includes the risk of hepa- totoxicity, QT interval prolongation, hyperglycemia, and pancreatitis. The clinical trials had less than 1% of patients having concurrent el- evations in ALT greater than three times the ULN and total bilirubin greater than two times the ULN with normal alkaline phosphatase. QTc interval prolongation occurred in patients receiving ceritinib in clinical trials and should be monitored throughout treatment as it can lead to cardiac arrhythmia and sudden death. Serum glucose levels should be routinely monitored before and throughout treatment with ceritinib since hyperglycemia can occur. The clinical trials also showed pancreatitis occurring in less than 1% of patients on ceritinib, but there has been one report of a pancreatitis-related fatality. There are recom- mendations to monitor lipase and amylase prior to starting treatment with ceritinib and periodically during treatment. Depending on the se- verity of laboratory abnormalities, the medication should be held and dose reduction recommendations can be found in Table 1 of the pack- age insert. Due to the potential seriousness of pancreatitis, the patient counseling information recommends that patients starting therapy with ceritinib be counseled on the signs and symptoms of pancreatitis. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ ucm458065.htm

Darbepoetin alfa (Aranesp)
The increased possibility of mortality, myocardial infarction, stroke, and thromboembolism has been edited in the warnings and precau- tions section to specify “adult patients” in Table 2 of the package labeling. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm458055.htm

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