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DRUG EVALUATIONS AND COSTS

What we provide. We evaluate data on drug efficacies, side effects and drug approval processes. The nature of our analyses can be judged from our publications on the clinical and commercial issues surrounding the blockbuster cancer drug Bevacizumab (Avastin).

The example of Avastin. All oncologists want the best of care for their patients, most of whom believe that Avastin is a life saver in metastatic breast cancer. However, most doctors are so busy tending to their ill and anxious patients, as well as dealing with the administrative burden of invasive healthcare bureaucracies, that they have little time to analyze the clinical trial data upon which their treatment is based. Our analyses and those of our Affiliates bring clarity to this therapeutic area. The key issue is a simple one; what do the clinical data, rather than the marketing, tell us about Avastin?

The Dr. Ian Hainespublished data on a number of cancer drugs and the clinical dosages at which they are administered, have been examined by Dr Ian Haines (pictured) of the Melbourne Oncology Group, Cabrini Hospital and the Department of Medicine, Monash University, Melbourne, Australia. His findings were published in the Journal of Clinical Oncology and in the The New England Journal of Medicine. The data reveal that there is no correlation between Progression-Free Survival or Overall Survival and the Quality of Life of women treated with Avastin.

What then are the benefits of this expensive treatment which neither keeps the patient alive longer, nor feeling better? What implications are there for Healthcare costs to governments and to individuals?

Women with metastatic breast cancer can pay nearly $100,000 per year for Avastin treatment and this highlights the significant financial burden to patients and to the healthcare systems worldwide. Healthcare costs are undergoing exponential increases as a percentage of GDP in many countries with cancer drugs representing 40% of all Medicare drug expenditures in the USA. The direct personal cost to patients of Avastin and other blockbuster drugs such as Herceptin, Erbitux and Vectibix can have a devastating effect on the financial well being of many patients. As pointed out by Dr Haines, one way in which escalating cancer healthcare costs need to be addressed is by using the minimum effective doses of drugs, rather than maximum tolerated doses of any treatments.

AVASTIN, GENENTECH AND THE FDA

Clinical trial data and the approval process. The Oncologic Drugs Advisory Committee of the FDA reported in December 2007 that the clinical trial data submitted by Genentech did not warrant the approval of Avastin in combination with Paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2 negative breast cancer. With the exception of venous thromboembolic events, all other side effects occurred more frequently in the group being treated with Avastin. These patients exhibited hypertension, proteinuria, arterial thromboembolic events with cerebrovascular ischemia, congestive heart failure, gastrointestinal perforation and fistula, as well as neutropenia and infection.

The committee ruled that the data presented to it were seriously deficient. It stated that the quality of life of patients treated with Avastin "went down" and it clearly stated that Genentech "didn't show they're living better and...didn't show that they're living longer". The committee emphasized that Genentech's submission "doesn't come close to what we would consider for a credible claim for any quality of life, especially with no differences being shown".

Specifically, in the case of the radiographic scans used to measure cancer progression, the radiologists reviewing these data were unable to agree on whether the cancer had progressed in the majority of the patients. To help resolve this very serious discrepancy, the scans were subsequently analyzed by an Independent Review Facility (IRF). In many cases where the radiologists found cancer progression, the Independent Review Facility did not find progression. In many cases where the radiologists did not find progression, the IRF found progression. In addition, Genentech was unable to provide scans for over 30% of the patients within the requisite time frame and some patients received longer Avastin treatment and more cycles than those not receiving Avastin. Given the lack of credibility of the data, this committee recommended against approval.

While awaiting a final decision by the head of the FDA, Genentech's president of product development, Susan Desmond-Hellman, stated in the Wall Street Journal that marketing Avastin to fight breast cancer "is important from a business perspective". Furthermore, William Tanner, an analyst with Leerink Swann and Co summed up the prevailing corporate attitude in the Wall Street Journal. If Avastin was not approved by the FDA then; "It’ll be a disaster. Sales growth could go flat or negative if people get yanked off Avastin".

In February 2008, the Head of the FDA, Andrew von Eschenbach, ignored the recommendations of his own Oncologic Drugs Advisory Committee and approved Avastin, despite the data that Avastin neither extended the lives of these women, nor improved the quality of their lives. The Director of the Center for Clinical Trials at Johns Hopkins University, Kay Dickersin, has stated that the tragedy of the FDAs decision is that it put commercial interests before those of breast cancer patients.

Our analyses. Our evaluation of Avastin illustrates the manner in which we examine the efficacies of drugs from the most basic research findings to the clinical and therapeutic levels.

 

 

2008, Haines, I. E. & Miklos, G. L. G. The New England Journal of Medicine, 358, 1637. Paclitaxel plus Bevacizumab for metastatic breast cancer.

2007, Haines, I.E. Journal of Clinical Oncology, 25, e31-e32.  A positive step forward, but more needed to maximize cost benefits of new-generation cancer therapies.