Tag Archives: Clinical Trials

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The tide is turning. Finally!

It has been four decades since the initiation of President Nixon’s “War on Cancer”, but never have the signs for victory looked so encouraging. This is an exciting phase in cancer research, so much so that some in the field are even using the “c” word. Cure!

So what is happening in the world of cancer therapeutics? And where are we headed? This was the topic of the Super Session: “A New Paradigm in Oncology Treatment” on Tuesday, June 24, 2014 at the 2014 BIO International Convention.

The thought-provoking discussion in this session reviewed current approaches and obstacles in oncology treatment, and discussed the way forward. Moderated by Susan Schaeffer of BioCentury, the panelists included:

  1. Ronald DePinho, MD Anderson Cancer Center
  2. Peter Lebowitz, Janssen Pharmaceutical Companies of J & J
  3. Bahija Jallal, AstraZeneca and MedImmune
  4. Robert Hugin, Celgene Corporation
  5. Jeff Allen, Friends of Cancer Research
Big Data, Cancer Therapeutics
Panelists at the Super Session "A New Paradigm for Oncology Treatment" (from L to R): Susan Schaeffer, Ronald A. DePinho, Peter Lebowitz, Bahija Jallal, Robert Hugin, Jeff Allen (Image Credit: BIO via Flickr)

Advances in Cancer Biology and Medicine

Developments in the omics fields have enabled scientists to molecularly characterize different cancers. Since each person’s cancer is different, the ability to profile a cancer is proving to be a valuable tool in the clinician’s armamentarium. In addition, we are witnessing the rapid development of newer targeted drugs. In the year 2012, the US Food and Drug Administration approved 39 targeted drugs for cancer (18 in the year 2013). Owing to these factors, oncologists can now develop personalized medicine approaches to treat cancer patients.

During the panel discussion, Peter Lebowitz agreed that better understanding of the disease biology has driven this progress; however, he hopes that technological advances would help us, especially to understand the tumor microenvironment, since that is crucial for cancer growth and maintenance.

Cancer Immunotherapy

With the advent of successful immunotherapy, the possibilities for cancer therapeutics have expanded even further. The success of immunotherapy over the past few years is just becoming obvious; it has succeeded in prolonging disease-free survival in patients with aggressive malignancies, such as non-small cell lung cancer and melanoma. Previously, clinicians rarely saw such durable responses with targeted therapies.

“Immunotherapy is definitely transforming the way we look at cancers,” said Bahija Jallal.

Ronald DePinho is excited by the success of immunotherapy and believes that it is the best approach for solid tumors, which are highly heterogeneous. However, he feels that we cannot entirely overlook targeted therapy. According to both DePinho and Robert Hugin, the ideal approach would be to use combinations in ways that produce synergies.

Regarding the use of immunotherapy, Lebowitz had a word of caution. “Often our dogma gets us in trouble” he quipped.

Lebowitz insisted that we should study and understand how each therapy acts, before using combinations in the clinic. This would prevent counter-productive effects of either therapy on cancer, when administered together.

Novel Approaches to Clinical Oncology

With better disease understanding, clinicians are matching targeted therapies to cancers. It is clear now that the one mutation-one drug paradigm for treating cancers is a gross over-simplification and does not work in the clinic. Successful cancer treatment requires the use of a panel of biomarkers to identify effective therapy. Generating these biomarker panels is possible due to newer technologies in the fields of genomics and proteomics. Further, in order to identify effective therapeutic options, innovative algorithms are required that account for the complexity of cancer and make predictions.

Apart from therapies, the field of clinical cancer medicine is shifting towards innovative clinical trials, such as the recent Lung-MAP trial – the first precision medicine trial from the National Clinical Trials Network. This is a multi-drug, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer that will be conducted under a public-private collaboration. Such emerging public-private collaborations may hold the key to future success in developing disease-targeted therapies.

The world of cancer research, academia and industry, represents an ecosystem. The key to success in this ecosystem is collaboration – integrating research data and clinical data, and sharing it freely between academia and industry. This synergistic collaboration will benefit both clinicians and researchers – to draw conclusions, to facilitate clinical decision-making, and to drive research.

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Consider a case where a patient has a disease with high mortality and no effective treatment available. A new experimental drug is now being tested in a clinical trial. However, this is a randomized clinical trial, which means that it will have a treatment group and a placebo group (that does not get the actual drug). Is it really ethical to include a placebo group in case of a disease with no other treatment options? Are we effectively condemning this and many other patients to death by assigning them to the placebo group – albeit randomly?

In such cases, clinical trial design presents a major ethical dilemma in the area of drug development. This and other ethical dilemmas were discussed at length at a special session “The Bioethics of Drug Development – You Make the Call!” on Monday, June 23, 2014 at #BIO2014 the 2014 BIO International Convention.

Una Ryan from Bay Area BioEconomy Initiative feels that the “old way is broken”. A previous advocate of the randomized control trial, she thinks that in the era of big data, it is possible to design open-label trials with no placebo controls and yet draw meaningful conclusions by comparing data with historical controls (control groups from previous studies and from clinical data on the disease).

Richard Moscicki, Deputy Center Director, Science Operations at the US Food and Drug ADministration (FDA) agrees that randomized control trials may not always be the best way to conduct trials but in some cases, are “the most acute tool” for us to show efficacy and obtain regulatory approval for drugs. A factor that may make open-label trials difficult is the lack of good historical control data in some cases. However, the panelists agreed there is no need for randomized control trials for drugs that have clear disease reversing effects.

Russell Medford from Salutramed Group had similar views and said that randomized control trials, though currently the gold standard, are not always required. He advocates a frank, open discussion with the FDA while designing trials.

All panelists agreed that in today’s age, there is room for innovative trial designs, such as adaptive clinical trials or open-label clinical studies. It cannot be overstated that, especially for patients with lack of treatment options, we need to identify the optimal approach for designing clinical trials and find a middle ground.

Drug Pricing and Ethics

Finally, drug pricing and access is another thorny issue in the bioethics arena. Most drugs that get approved are introduced into the market with an intimidating price tag. But the fact remains that the drug-pricing curve has a sharp rise and a sharp fall. This fall in prices comes as drugs from competitors with similar efficacy enter the market. Prices drop further as generics enter the market once companies lose their sole monopoly over drugs.

Drug Development Bioethics
Drug Pricing and Bioethics (Image Credit: www.atg.wa.gov)

The calculation of drug pricing is aimed at increasing return on investment for a company; drug companies have to consider the cost of successfully bringing a drug to the market – including the failures that never made it past the discovery or early development stages. With these calculations, the price tag on every approved drug ranges from anywhere between $1 billion to $12 billion. From a business point of view, companies need to take into account all these factors for long-term sustainability. Of course, business ethics tend to clash with healthcare ethics, necessitating the search for a middle ground. Most panelists were of the opinion that high drug prices are justified as long as they are “fair”.

There were other ethical issues to be considered too. Would it be prudent to incorporate differential pricing globally or have static pricing? What about pricing for drugs used in rare diseases that have a small market? And what about patients/patient groups unable to pay for the high costs of these drugs? These are some troubling questions that need a lot of thought and discussion among key players globally.

It was clear at this session that there is no one correct answer or solution to either of the ethical issues discussed at this BIO2014 session. These issues lie at the crossroads of business, healthcare, and public health. Stimulating a public debate and encouraging dialogue between the pharmaceutical companies, healthcare professionals, patient interest groups, and regulatory agencies would go a long way in navigating these ethical minefields.