Revoking Avastin’s Breast Cancer Indication: Right or Wrong?

The FDA has decided to begin the process of removing the metastatic breast cancer (mBC) indication for Avastin (bevacizumab). Roche stands to lose $1 billion in revenue, while women have one less option to manage their disease. Two questions need to be answered: (1) was this the correct decision given the evidence and (2) what will be the ripple effect(s) of this decision?

What happened to elicit this withdrawal?
Avastin was approved in 2008 to treat mBC based on data obtained from a single clinical trial (E2100) using the FDA’s accelerated approval process. Since then, four clinical trials have been conducted and the FDA has determined that Avastin does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks.

Was this the correct decision?
In my opinion, it was. Avastin is a good medication for its other oncology indications, but not for breast cancer. The lack of significant separation between benefit and risk makes it almost impossible to justify its use in patients with mBC. Furthermore, it’s difficult to rationalize the cost of Avastin, which is about $50,000 per year given the present data. With other options available for this patient group, and more negatives than positives, it was a logical decision.

What will be the ripple effect(s) of this decision?
This is where we need to pay particularly close attention. Several key events helped to shape the current Avastin situation. It is important to understand these, as they will affect the way we do business in the future.

• Accelerated approval: The essence of this program is to get drugs to market faster with less evidence than is typical and confirm a drug’s risk-benefit profile once more evidence becomes available. Over time, some drugs will fail to confirm the results of earlier studies, necessitating occasional revocations. For Avastin, this means the loss of a high-revenue indication. How do we adjust our brand positioning accordingly, depending on what the follow-up data show?
• Surrogate endpoints: Accelerated approval programs, especially in cancer trials, permit the use of surrogate endpoints, because assessing survival takes time. How should this impact the creation of a brand plan or promotional materials? How much effort should be dedicated to laying the groundwork for the data that follow? This is one of those rare cases where an approved drug needs work streams in medical affairs and marketing moving simultaneously and at the same speed.
• Risk-benefit or risk-benefit-cost: If Avastin cost $5,000 per year instead of $50,000 per year, would that have made any impact on the FDA’s decision? We do not know and may never know. However, several drugs in 2010 had been denied approval or additional indications based on their cost and the availability of cheaper, equally effective alternatives. Conducting superiority trials makes many people nervous, but if you have a high price point compared with your competition, it may be worth the risk.
• FDA going against advisory committee: Understanding the motivation for this decision will always be an exercise in speculation. The FDA is not, nor will it ever be, immune to the opinions of the masses. For the agency to break with its advisory committee, more than just science must have been part of the discussion, which brings us to…
• Influence of patients and their advocates: These groups are particularly well versed and not afraid to voice their opinions to the FDA on cancer issues. One might predict that the loss of any treatment option would be met with an uproar. Surprisingly, major patient advocacy groups were split on their thoughts about this decision. In one camp, patients who have done well on Avastin want it to be available and affordable. Another breast cancer advocacy group testified against Avastin’s initial mBC approval due to the use of surrogate endpoints. It appears that the advocate door swings both ways.

What will be the enduring lesson from this experience? Brand plans have an expiration date on them and need to be viewed as living entities. They need to be flexible and able to adapt to changing times. The luxury of strategic and tactical forecasting for 3-5 years down the road has become outdated. Staying nimble and informed might be the best future strategy.

Ken Ribotsky

Ken is a great deal more than just the president of a medical communications company. He is something of a hybrid. He’s part marketing manager, part creative director, and part copywriter. To the chagrin of his peers—but to the delight of his clients—Ken is a consummate perfectionist. As a former creative director for a high-end consumer agency, he challenged his creative teams to go beyond the mundane to produce work with real creative impact, something he’s just as fervent about today. From producing and directing TV commercials, to launching DTC and Rx-to-OTC switches, Ken brings his clients a world of experience in OTC pharmaceuticals as well as business, lifestyle, and high-end consumer products and services. Whether huddled with clients behind a mirror in a market research center in Houston, facilitating a strategic workshop in Madrid, or developing a global campaign either in the New Jersey or California office, Ken is always fully engaged, bringing “bestness” to all areas of his hectic but full life.