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Evidence-Based Oncology December 2015
Three Proposals to Reform the 340B Drug Discount Program
Rena M. Conti, PhD; Peter B. Bach, MD, MAPP; Michael Kolodziej, MD
"Financial Toxicity": A New Term, but Not a New Reality for Many Cancer Patients
Debra Madden
Is There a Mathematical Resolution to the Cost-Versus-Value Debate?
Bruce Feinberg, DO; Lincy S. Lal, PharmD, PhD; J. Michael Swint, PhD
Maximizing Value of Freestanding and Outpatient Hospital Setting in Cancer Care Delivery
Constantine Mantz, MD
Managing Costs and Enhancing the Value of Oncology Care
Surya Singh, MD; Christine Sawicki, RPh, MBA; Ken Vander Pyl; Alan Lotvin, MD
Eliminating a Barrier to Cancer Care through Universal Fair Access to Oral Chemotherapy Medications
Christopher Hansen
Impact of Oral Parity: A Personal Story
Christopher Hansen
Measuring Financial Toxicity in Cancer Patients
Pauline Lee, PharmD, and Jonas A. de Souza, MD
The Financial Impact of Cancer Care: Implications and Potential Solutions
Veena Shankaran, MD, MS
Patient Access to Oncology Care in ACA Exchange Plans
Caroline F. Pearson and Deirdre B. Parsons, MPP, MPH, MS
The Struggle Between Oncology Care Cost and Value
Joseph Alvarnas, MD
COA Payer Summit
Surabhi Dangi-Garimella, PhD
ACCC ICLIO meeting
Surabhi Dangi-Garimella, PhD
Currently Reading
FDA Updates: Oncology
Surabhi Dangi-Garimella, PhD

FDA Updates: Oncology

Surabhi Dangi-Garimella, PhD
Several new FDA approvals and research advances in oncology have the potential for improved outcomes among cancer patients.
Tagrisso Approved, but Can Patients With EGFR-Mutant NSCLC Afford It?

  AstraZeneca’s epidermal growth factor receptor (EGFR) inhibitor, osimertinib (Tagrisso), was recently approved in patients harboring T790M-mutated non-small cell lung cancer (NSCLC) who have regressed following treatment with other EGFR inhibitors.1 The approval comes within 3 years of the company having launched drug trials for osimertinib, which showed an objective response rate of 59%, and a sustained response of over a year.

Having specifically developed the drug for a subset of NSCLC patients, Astra- Zeneca collaborated with Roche Diagnostics to develop a companion diagnostic, the cobas EGFR Mutation Test v2, which detects EGFR mutations in NSCLC tissue samples.

While oncologists, including Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, have hailed osimertinib to have the potential to be the standard of care in EGFRm T790M NSCLC, the question now is how much will it cost the patient and the healthcare system overall, and, will this cost add value?

According to a company spokeswoman, a 1-month supply of this oral medication is estimated to cost nearly $13,0002—quite comparable with Pfizer’s Xalkori (prices at $11,500 a month) and Zykadia by Novartis ($13,200), both approved for treating Alk-mutated lung cancer. And, we have not yet started talking about the cost of the companion diagnostic test that will determine patient eligibility for osimertinib.

While previous estimates from AstraZeneca projected a $3 billion annual market for the drug, the news of Clovis Oncology’s competitor product hitting a snag in their FDA review could further open up the market for AstraZeneca. CO-1686 or rociletinib, which has shown promising results in EGFR-mutated (T790M) NSCLC patients, now needs additional data for FDA review.

Meanwhile, Diplomat Pharmacy, the largest independent specialty pharmacy in the country, has announced plans to offer osimertinib to a few select patients. “Diplomat is proud to support patient adherence and compliance with therapy through enhanced clinical outreach programs, with customized messaging, developed in collaboration with AstraZeneca, to patients through various stages of treatment,” said Gary Kadlec, president of the company, when making the announcement.3  

REFERENCES

1. TAGRISSO (AZD9291) approved by the US FDA for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer [press release]. Wilmington, DE: AstraZeneca; November 13, 2015. www.astrazeneca.com/our-company/ media-centre/press-releases/2015/TAGRISSO-AZD9291-approved-by-the-US-FDA-for-patients-with-EGFR-T790M-mutation- positive-metastatic-non-small-cell-lung-cancer-13112015.html.

2. AstraZeneca’s Tagrisso to cost $12,750 for a month’s supply. Reuter’s website. http://in.reuters.com/ article/2015/11/17/us-astrazeneca-cancer-tagrisso-idINKCN0T61J420151117?feedType=RSS&feed- Name=health&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+reuters%2FINhealth+%28News- +%2F+IN+%2F+Health%29. Published and accessed November 17, 2015.

3. Diplomat to dispense AstraZeneca Drug TAGRISS (osimertinib) [press release]. Flint, MI: Diplomat Pharmacy, Inc; November 16, 2015. www.prnewswire.com/news-releases/diplomat-to-dispense-astrazeneca-drug-tagrisso-osimertinib- 300179523.html.

Daratumumab Approval Yields the First Monoclonal Antibody, and Another Option, in Multiple Myeloma 

The FDA has approved daratumumab for patients with multiple myeloma who have previously been treated with at least 3 regimens.1 Daratumumab, which received breakthrough status 2 years ago, is the first monoclonal antibody approved for multiple myeloma.

The approval follows review of 2 open-label studies that included 106 and 42 participants. The first study (phase 2 MMY2002) saw 29% of patients with a complete or partial reduction in tumor burden that was sustained for at least 7.4 months. These patients had received a median of 5 lines of prior therapy. The second study (phase 1/2 GEN501) saw a complete or partial reduction in tumor burden of 36% of patients. These patients had received a median of 4 lines of prior therapy. Today’s approval is the first for a CD38 antibody and comes just 2 months after the drug was submitted for priority review.

Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, hailed daratumumab as another option for patients to turn to when their disease has developed resistance to all other existing therapies.

Some of the side-effects associated with the drug include infusion-related reactions, fatigue, nausea, back pain, fever, and cough. Daratumumab may also result in low counts of infection-fighting white blood cells (lymphopenia, neutropenia, and leukopenia) or red blood cells (anemia), and low levels of blood platelets (thrombocytopenia).

Daratumumab, approved under the FDA’s accelerated approval program, had an orphan drug designation.  

REFERENCE

1. FDA approves Darzalex for patients with previously treated multiple myeloma [press release]. Silver Spring, MD: FDA; November 16, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm.

A Cancer Prevention Trial Identifies Predictive Biomarker in Oral Cancer Development 

Oral premalignant lesions (OPL) can be risk factors for oral cancer, and chemoprevention strategies can be developed to stop or reverse the cancer.

A trial designed to test one such strategy—the Erlotinib Prevention of Oral Cancer (EPOC)—evaluated whether inhibiting the epidermal growth factor receptor (EGFR) could reduce oral cancer development in patients with high-risk OPLs. While the EGFR inhibitor being evaluated, erlotinib, did not improve cancer-free survival (CFS), the trial validated loss of heterozygosity (LOH) as a marker of oral cancer risk and was associated with increased copy number of the EGFR gene.

The EPOC study, conducted between November 2006 and July 2012, recruited 395 participants with OPL in 5 academic institutions in the United States. Following LOH profiling, 379 patients were classified as high-risk (LOH-positive) or low-risk (LOH-negative). Treated with 150 mg/day erlotinib or placebo for 12 months, the trial followed patients for 35 months. One hundred and fifty of the 254 LOH-positive patients were randomized—75 received erlotinib and 75 were on placebo. The 3-year CFS rate was 70% and 74%, respectively, when comparing these 2-patient cohorts. However, 3-year CFS of LOH-negative patients was much better than that of LOH-positive patients—87% versus 74%, respectively. Further, the authors deduced a correlation between EGFR gene copy number and LOHpositive status, as well as EGFR gene copy number and lower CFS. A serendipitous finding of the trial was that patients who developed a skin rash, a side-effect of erlotinib, had better CFS.1

According to study author William N. William Jr, MD, associate professor at MD Anderson, “One of the greatest challenges in developing chemopreventive agents is to identify the population at highest cancer risk. Not all patients with an oral premalignant lesion will develop cancer. By developing a molecular test that can identify those at highest risk, we hope to focus future preventive efforts on these specific individuals.”2

The authors write that, while their results support using LOH testing as a prognostic tool in routine clinical practice, they do not support erlotinib use in this setting. Another feather in the cap of personalized medicine in the preventive setting.  

REFERENCES

1. William WN Jr, Papadimitrakopoulou V, Lee JJ, et al. Erlotinib and the risk of oral cancer: the Erlotinib Prevention of Oral Cancer (EPOC) randomized clinical trial [published online November 5, 2015]. JAMA Oncol. doi: 10.1001/jamaoncol. 2015.4364.

2. First precision medicine trial in cancer prevention identifies molecular-based chemoprevention strategy. EurelAlert! website. www.eurekalert.org/pub_releases/2015-11/uotm-fpm110415.php. Published November 9, 2015. Accessed November 10, 2015.

Exceptional Response in Brain Tumor Patient Instills Confidence in Personalized Medicine 

Ayoung man, less than 40 years old, with recurrent craniopharyngioma (pituitary tumor) harboring a BRAF V600E mutation, showed a dramatic response when treated with BRAF V600E inhibitors—85% reduction in tumor volume. This case has the “potential of completely changing the management of papillary craniopharyngiomas,” according to study author Priscilla Brastianos, MD, of the Massachusetts General Hospital (MGH) Cancer Center.1

The study, published in the Journal of the National Cancer Institute,2 reports on the case study of a patient who came to the emergency department at MGH, 7 months after having undergone surgery to excise a brain tumor. A CT scan of the patient, who complained of confusion, impaired vision, severe headaches, and vomiting, revealed a 4-cm cystic tumor. Six weeks following partial removal of the tumor, the patient was brought back and underwent additional surgery. At this point, the tumor was confirmed to carry a mutant BRAF. Another unsuccessful surgery and a recurrence in 2 weeks prompted the providers handling the case to treat the patient with the BRAF-V600E inhibitor dabrafenib, currently approved for the treatment of patients with unresectable or metastatic melanoma harboring the BRAF-V600E mutation.

A dramatic response was seen within 4 days of treatment, with a 25% tumor shrinkage, the authors report. Following a 50% shrinkage in tumor by day 17, the authors added a MEK inhibitor, trametinib, which has been approved for use in patients expressing a mutant BRAF (V600E or V600K).3 When the tumor reduced to 80% its original size, another surgery removed any accessible tumor at day 38 and drug treatment was stopped a week later, followed by radiation. The patient has been reported to be symptom–free for a year. Another extremely important outcome of the study was the ability to detect circulating tumor cells, which carried the BRAF mutation, using a blood-based assay. For patients with a brain tumor, a noninvasive test can be a tremendous advantage and can significantly reduce patient morbidity.

“It is quite remarkable how quickly we have been able to go from identifying the genetic driver of papillary craniopharyngiomas to testing the idea in a patient that needed help. It was only last year that, along with Dr Brastianos and colleagues, we first described in Nature Genetics that nearly all papillary cranionpharyngiomas have mutations in BRAF,” said co-senior author Sandro Santagata, MD, PhD, of Brigham and Women’s Hospital’s Pathology Department.  

REFERENCES

1. Targeted treatment produces rapid shrinkage of recurrent, BRAF-mutant brain tumor. ScienceDaily website. www. sciencedaily.com/releases/2015/11/151106153141.htm. Published November 6, 2015. Accessed November 9, 2015.

2. Brastianos PK, Shankar GM, Gill CM, et al. Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst. 2015;108(2):pii:djv310. 3. Trametinib. FDA website. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm354478.htm. Accessed November 9, 2015.

Another First for Nivolumab: Approved as Frontline for BRaf Wild Type Melanoma

 
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