Breast Cancer and Avastin, the Ongoing Saga

As many are now aware, in November of 2011, the United States FDA withdrew approval for bevacizumab (Avastin) for the treatment of breast cancer. Medicare and the National Comprehensive Cancer Network  (NCCN) are now re-examining their guidelines. In the interim, reimbursement for Avastin is a patchwork of approvals and denials across the country.

Into this mix comes an interesting concept apparently floated by Roche’s European affiliates. Described in a brief press release was the suggestion that Roche might be prepared to attach Avastin reimbursement to its efficacy. That is – Roche would only demand payment from patients and third party payers if the treated patient revealed objective evidence of response. This is an interesting idea!

The concept of conditional reimbursement is extremely intriguing. Contrary to contemporary reimbursement policy, the purveyors of therapy would only receive compensation if they could prove benefit, not mind you, benefit in the broad brush Phase III tiny statistically significant result (e.g. the FDA approval of erlotinib plus gemcitabine in pancreatic cancer for a median survival advantage of 10.6 days!), but instead very real benefit on a patient-by-patient basis.

We use erlotinib plus gemcitabine, as well as Avastin combinations, to great benefit for many of our patients and applaud the availability of these drugs and combinations. But we never, just give them. Were the federal government, major payers or HMOs to be prepared to reimburse novel therapies predicated on their efficacy, we might envisage a meaningful advance in cancer therapeutics.

Today, few small laboratories, start-up companies and early stage biotech firms have the resources to marshal multi-million dollar clinical trials to test new therapies. This may in part be why advances in cancer therapy are moving so slowly forward.  The barriers to entry are insurmountable, causing many good ideas to fall by the wayside for lack of the hundreds of millions of dollars required to achieve FDA approval and Medicare reimbursement. But what if on an individual basis, reimbursement policies reflected the most meaningful of all endpoints – individual patient response and survival. Even the largest pharmaceutical companies are now coming to realize that despite their clout they too are suffering under the guidelines forced upon drug developers in this era of ever increasing regulation.

This is a concept worth pursuing. Let’s see where it goes.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to Breast Cancer and Avastin, the Ongoing Saga

  1. I understand the arrangement was prompted by a law passed last year in Germany that allows insurers to bargain over prices for new meds and comes as insurers try to link outcomes with reimbursement as health care costs continue to spiral.

    Roche has also agreed to reimburse the cost if patients take more than 10 grams of Avastin in a year, which is equivalent to about seven months of therapy for breast, kidney, and ovarian cancer patients because of the higher dosages such cancers require.

    Such a deal offers Roche a good deal of upside in the absence of a genetic marker that can indicate which patients would most benefit from Avastin. The drugmaker is under pressure since the FDA decided to remove the indication for breast cancer treatment after an extraordinary review.

    This is starting to sound very much like the situation with Herceptin years ago. Herceptin drew fire from the FDA and other groups, including ASCO, because of its expense and the fact that it helped only 11-20% of patients who received it.

    There were tons of data showing that pathologists were “over-calling” the cases of HER2-positive via IHC and manual microscopy. There were tons of data showing that use of automated image analysis virtually eliminated “over-calls” and very reliably normalized IHC scoring among pathologists of all levels of experience.

    Even Dennis Slamon (one of the inventors of Herceptin) had told (then) Genentech, they had a drug that is even better than they knew. It only has to be administered to the right patients. The disinterest on the part of Genentech was palpable.

    In the end, the FDA did force them to work with someone to develop a reliable pharmacodiagnostic test. Genentech put their muscle behind FISH.

    However, in the end, they couldn’t completely supplant low-tech IHC and both received FDA approval. Herceptin is now approved for patients who are positive via FISH or IHC, even though patients considered Her2-negative using both tests benefited from Herceptin.

    In other words, the problem was never solved. It’s an inconvenient truth which everyone involved conveniently chooses to ignore. Sheesh!

    It is possible to correctly administer Avastin by measuring the vasculature of a tumor with an anti-angiogenesis microvascular viability aspect of the functional profiling platform?

  2. Rich66 says:

    GSK offered something similar to (not)NICE:

    “We disagree with NICE’s decision and believe Tykerb is a valuable and important treatment for eligible patients,” Rea said in an interview. “This decision is particularly frustrating in that we have been flexible in our pricing structure by offering to bear the cost of Tykerb for the first 12 weeks of treatment. The NHS would then only pay for patients that continue to receive clinical benefit.”

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