Will Oncology and Pathology Unite on Molecular Testing?

Posted by Judi Space on Wed,Mar 27, 2013 @ 07:00 PM

For more than a decade, we have been listening to the leaders in cancer research tell us that in order for targeted therapy to work, we must be able to identify who will benefit from it through the use of predictive biomarkers. This is the essence of personalized medicine.

Is molecular testing the key to targeted therapies and a solution to a one-size-fits-all approach?Molecular testing (MT) is becoming the new paradigm for determining an individual cancer patient's course of treatment. Although it is fairly widespread in large academic cancer centers, community hospitals and cancer clinics, where most cancer patients are treated, are often completely out of the loop.

Recently the Association of Community Cancer Centers has sought to better understand the scope of this problem through a survey of its members (1). This survey polled the member institutions' administrators, oncologists, pathologists nurses, and pharmacists (N=52 institutions) about policy, practices, and proceedure related to MT as well as reimbursement issues.

Implementing Molecular Testing: Education of Stakeholders is Key

There are many challenges to the implimentation of MT in the community oncology setting(1).  Chief among them is unwillingness of various stakeholders to work together to make MT a routine proceedure for all newly diagnosed cancer patients. The reality is that testing is already being done on a very limited basis for breast cancer patients (HER2, and ER/PR), but the cancer centers appear to balk at the expansion of similar testing in other cancer indications.(2)

It also represents a great new opportunity to improve the coordination between pathologists and oncologists.

In order to implement MT, The ACCC survey indicated that there should be "champions" that drive the institution toward a coordinated testing program. Most often these champions come from the ranks of the oncologists. They must educate their peers and the institution's administration about the necessity for having a MT policy/proceedure to decide how and when specific tests will be implemented.

Will Oncology & Pathology Come Together Over MT?

Can oncology and pathology unite over molecular testing?The lack of collaboration between pathologists and oncologists is one of the things that's holding molecular testing programs back. Many physicians can't seem to agree on whether MT is necessary, and when. Some don't see the value in personalized medicine, while cancer center administrators see it as simply a line in the budget and are unwilling to spend the time and money in an environment of competing interests.

However, there is safety in numbers. By uniting on the molecular testing issue, oncologists and pathologists will have a greater chance of convincing administrators its necessity.

Is Molecular Testing Costly or Cost Effective?

One of the drawbacks to molecular testing programs is the cost of testing. The decision for doing MT may lie with the payer, rather than the patient's specific needs.  Each assay can run as much as $7,000, which can make insurance companies unwilling to cover the cost in many cases.

However, most oncologists and pathologists agree that molecular testing can actually save money in the long run. The detailed, personal information that it provides can guide an otherwise uncertain treatment plan. A negative test result can save a lot of money on expensive, targeted therapies.

In order for progress to take place, continuing education is essential. This is true of both the medical oncologists and the pathologists. In the rapidly evolving world of cancer drug development, new molecular tests will emerge on a regular basis which will help choose new options for treatment where there were none before.  Pathologists and oncologists must work together to use the test results to guide treatment by identifying who will benefit from specific targeted therapy regimens. 

References

(1)http://accc-cancer.org/education/molecularTesting-Overview.asp

(2) http://obroncology.com/obrgreen/article/Molecular-Testing-Preparing-for-the-New-Normal-in-Community-Oncology


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Oncology, Predictive Biomarkers, Targeted Therapy, Drug Development, Molecular Testing, Personalized Medicine

NCI Improvements: Drug Development Opportunity for Pharma and Biotech

Posted by Judi Space on Tue,Mar 12, 2013 @ 06:00 PM

Three years ago the Institute of medicine declared that the nation’s cooperative group system for conducting clinical trials was so moribund as to not be an effective vehicle for the generation of scientific data in a timely fashion. In a report generated in 2010, the IOM recommended that the number of cooperative oncology groups be reduced from 10 down to 5[1], improve speed and efficacy of the trial processes as well as incorporate new scientific discovery into clinical protocols. Along with this, the report said it was critical to create a data platform that would assist in the administration of trials across all of the remaining cooperative groups. This would be a system to which both large academic centers and community cancer centers could adhere.

NCI Less of a Barrier; More of a Facilitator

To a large extent, the NCI was  a barrier to the conduct of clinical trials due to their role of providing oversight. The IOM report urged that NCI become part of the solution by helping to prioritize and design trials as well as directing patients to relevant studies so that enrolment could proceed more rapidly. In addition, CMS was tasked with removing barriers to enrollment by supporting appropriate costs associated with patient treatment during the trials.

Efforts Bearing Fruit

Now, nearly three years later, we can see the effects of this report. In a two day workshop[2] that took place in Washington last month, improvements in the national cooperative group trial system were documented[3]. Among the improvements noted:

  • The time between concept and activation of phase II trials sponsored by NCI has shrunk by more than a third. Trials not meeting timelines will be terminated!
  • Time to activation for phase III trials has been halved since the overhaul process began
  • The number of cooperative groups has actually been cut in half – now there are only 5
  • A common enrollment and data management system has been put into place
  • Patients can enroll 24/7 and they may participate in ANY Ph III trial in the system regardless of origin
  • There are now  standardized agreements for industry collaborations
  • A new  review process has been launched for grading the quality of trials
  • Integrated biospecimen banks are being created

Still to come are more innovative Ph II trials based on molecular biology of the tumors and the extensive use of biomarkers and genomic profiling.

Ecology of Clinical Trials

Community Cancer Centers are Key

The key to moving clinical research forward more rapidly will be enhanced participation of community cancer centers. Investigators at these sites are often hesitant to take part as many of the costs associated with the trials are not covered.  After more provisions of the Affordable Care Act go into effect, next January, this may no longer be a barrier. Federal law will require insurers cover the cost of routine patient care in clinical trials.

Design and Conduct of Trials Improving in UK As Well 

Interestingly, the US is not the only place that has had a sea change in the way it conducts clinical research for cancer. Over the same period, the UK’s National Health Service has recognized that clinical research is an important part of its mission, and therefore has provided incentives for patients to participate in trials. The key here is that cancer patients do not get access to novel agents unless they participate in the trials. The result is a trials network that rivals anything in the US but existing in a much smaller country.

 

Implications for Drug Development:

Drug approval process improving in the UK as well as the US

Pharma  and biotech companies can harness the power of the NCI to get things done faster than they have become accustomed to in the past, and the improvements will continue into the foreseeable future. This is also good news for cancer patients who will be able to access more cutting edge clinical trials no matter what part of the country they are from.

 


[1] http://www.iom.edu/~/media/Files/Report%20Files/2010/A-National-Cancer-Clinical-Trials-System-for-the-21st-Century-Reinvigorating-the-NCI-Cooperative/NCI%20Cancer%20Clinical%20Trials%202010%20%20Report%20Brief.pdf

[2] http://www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/2013-FEB-11/Agenda%20-%20IOM%20ASCO%20Implementation%20Workshop.pdf

[3] http://www.nap.edu/catalog.php?record_id=18273


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: FDA, Drug Developers, Oncology, Predictive Biomarkers, Targeted Therapy, Data Standardization, NCI, Cancer Drug Development, Oncology Clinical Trial Design

Breast Cancer Drug Development - Targeting HER2 Activating Mutations

Posted by Judi Space on Thu,Jan 10, 2013 @ 09:00 AM

A Possible Development Pathway for Biotech Companies with PanHER Inhibitors?

Many Breast Cancer Patients Not Helped by Herceptin

For more than ten years oncologists have been aware of the role that Herceptin (trastuzumab, Roche/Genentech) has played in extending the lives of women with HER2 overexpressed breast cancer. Herceptin works by blocking the HER2 receptor from receiving activating stimuli from outside of the cell. In addition there is a second agent, Tykerb (lapatinib, GSK) which is able to block signaling from the tyrosine kinase domain of the receptor, inside the cell. Still, there are many patients who are not helped by these agents. These targeted therapies work when the receptor is overexpressed, but may not work when the receptors are mutated.

Breast cancer drug development - exposure to neratinibSomatic Breast Cancer Mutations Identified

At December’s San Antonio Breast Cancer Symposium, there was a talk given by Ron Bose from Washington University, about other perturbances of the HER2 receptor[1][2]. Over the last year, the Cancer Genome Atlas Breast Cancer has conducted genome sequencing of breast cancers. This endeavor has identified several somatic mutations that appear on the HER2 receptors in some breast cancers. A majority of the mutations were found in the kinase domain of the receptor. Most of the lesions analyzed were considered HER2 negative as they did not achieve the 3+ score in IHC testing.  

Ph II Trial of Neratinib in Breast Cancer Patients

Because the mutations cause constitutive activation of the receptor (it is always turned on), Herceptin cannot block its signaling from outside of the cell. The mutations are rare, and it is estimated that only about 5000 women in the US with breast cancer would have them. In cell line studies, Tykerb has some effect on cells with these mutations, but the agent that appears to have the most activity is neratinib (Puma), a “pan-HER” inhibitor. To that end, there will be a fairly large Ph II trial of neratinib in breast cancer patients who test negative for HER2 amplification but positive for these somatic mutations.

Breast Cancer Drug Development - Targeting Somatic Cancer Mutations

There is precedent for targeting somatic mutations in malignant lesions. Even in the same family of receptors, there are three agents with activity against EGFR: Iressa (gefitinib, AstraZeneca), Tarceva (erlotinib, Roche/Genentech) and afatinib (Boheringer Ingleheim). This has implications for the larger world of breast cancer biotech drug development targeted at the EGFR family of receptors as there are many “pan-HER” inhibitors in development that could potentially be used to treat tumors with these mutations.

Barriers to Breast Cancer Drug Development

The biggest barriers for development would be working up accurate testing systems to detect the mutations as predictive biomarkers of drug efficacy, and then getting these tests included in the battery of diagnostics used to analyze both primary breast tumors and recurrent disease.     


[1] Bose, R Activating HER2 mutations in HER2 gene amplification negative breast cancers, SABCS December 2012, S5-6


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Oncology, Predictive Biomarkers, Targeted Therapy, Breast Cancer, Breast Cancer Drug Development, Breast Cancer Oncology, Breast Cancer Therapy

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