The world's steadily growing oncology market features key elements that are common to all competitors in the category: a highly respected sales forces, sophisticated and deeply involved patients and caregivers, clinically entrepreneurial physicians, and a dynamic global regulatory environment. Yet the uncharted territory of cancer breakthroughs demands that pharma marketers temper a strategy of progressive risk with caution.

Savvy Patients

Nobody wants to deny treatment to cancer patients who are eager, if not desperate, to try anything that could offer them hope for a longer or better life. They may not have to, now that genomic and proteomic science promises treatments targeting the molecular cause of the disease while circumventing the harsh side effects of traditional therapies. In addition, and perhaps more important, is that such discoveries may hold promise for treating other diseases. Recently approved Campath (alemtuzumab), for example-Ilex Oncology's human monoclonal antibody for refractory B-cell chronic lymphocytic leukemia-has demonstrated value as an aid in organ transplantation and in treating rheumatic diseases and neurologic disorders such as multiple sclerosis.

Patients, their families, and caregivers-often guided by a network of support groups and Web-based medical information-are eager to enroll in clinical trials to gain access to promising treatments. Well informed about various compounds and their mechanisms of action, patients facilitate the screening process, effectively self-selecting for the trials best suited to their conditions. Once enrolled, cancer patients are more likely than most to be "by-the-book" compliant with their treatment protocols, and they often know as much about genetic testing and targeting as oncology residents do, such as the existence of markers for treatment susceptibility, especially HER-2 in breast cancer and PML-RAR in acute leukemia.

Armed with that information, many patients seeking tests for the markers implicated in their diagnosis are beginning to overwhelm local cancer centers and hospital labs. For that reason, educational efforts for mass patient recruitment are unnecessary. Finding eligible clinical candidates who are not already committed to lengthy studies is the real challenge.

Susan Noble-Kempin, RN, MS, OCN, national director of research and administration at Salick Health Care, says such challenges have forced a complete change in the way her centers conduct clinical trials. "We have to approach patients differently than we did for traditional chemotherapy," she says. "Now we have to send out their tissues to identify markers, and it's difficult for patients, waiting to find out if they're going to get into the study. We have to offer them a menu of trials to choose from, whereas in the past, we rarely had competing trials going on at the same time."

Patients are also becoming increasingly concerned about their legal rights to their own biological material. Aware of the longtime debate about the application of property laws to biomedical research, patients are finding ways to turn the informed-consent routine into a comp-licated legal and ethical conundrum.

To lend perspective to that issue, Jack Snyder, MD, JD, former president of the American College of Legal Medicine, offers a scenario based on a well known California case involving a cancer patient who sued for the property rights to his spleen, which was successfully removed by a UCLA surgeon and subsequently used for a fruitful research project.

"If I work for a company that takes your tissue and makes big money from it, and I want to patent some aspect of what I learned from your DNA, what rights do I have?" asks Snyder. "We've known for more than 20 years from the Supreme Court that there are certain types of new plants and other biological entities that can be patented. How does that apply to companies, doctors, and their patients?"

Savvy patients-many of whom subscribe to the same peer-reviewed journals as their oncologists-know that placebos are passe in cancer research. They know that in a double-blind study, they risk getting the "gold standard" for their diagnosis instead of the experimental treatment. But to them, the gold standard is simply the old standard-and they've been there. "As publicity about new compounds gets out to the public, patients want the newer treatment rather than going into a randomized study," says Noble-Kempin.

Often, the most sophisticated patients become the most supportive advocates, not only for their own care but for pharma companies' regulatory agendas as well. Few treatments for rare, life-threatening disorders would be anywhere near commericalization today if not for the steadfast advocacy of vocal organizations such as the Multiple Myeloma Research Foundation or the National Organization for Rare Disorders.

In one recent example, Novartis' Gleevec (imatinib) sailed through FDA review to approval in a record-breaking two-and-a-half months. Largely because of the overwhelming demand from leukemia patients and advocates, the product needed only 32 months from the time the first clinical trial participant swallowed a pill until the filing of a new drug application. All told, the company got its product to market in six years-about half the usual time.

Eager Physicians

There are more than 15,000 members of the American Society of Clinical Oncologists, the world's leading organization for oncologists, oncology nurse specialists, and other technical professionals involved in cancer patient care. Though they represent a relatively narrow prescriber base, oncologists are by far the main influencers of patient care, because, despite patients' knowledge, they almost always rely on their doctors for the final decision about their treatment.

Those facts provide the basis for an important question: If so few prescribers write scrips for highly specific treatments for a small group of eligible patients, how can any one cancer treatment become a blockbuster? A single phrase explains why: off-label usage.

Oncologists regularly experiment with treatments they believe will give their patients a chance, regardless of approved indications or labeling. Understandably, if something works, such restrictions mean very little in life-and-death situations. In Gleevec's case, the New York Times ran a story within days of its approval for use in chronic myeloid leukemia about its pro-mise for another type of deadly cancer, gastro-intestinal stromal tumors. The article quotes a doctor from the prestigious Memorial Sloan-Kettering Cancer Center singing the medicine's praises for its efficacy in "one of the hardest cancers to treat." The doctor went so far as to say that it "might even be a cure."

It is commonly estimated that 50-80 percent of all oncology prescriptions are for off-label uses. Those prescriptions may lead to short-term sales growth-immediately after FDA clearance, in some cases-for a variety of agents oncologists believe can be effectively used in multiple diagnoses or, more commonly, in combination with currently used cytotoxic chemotherapies.

"There is so much combination use-sometimes three or four together-that the regulatory challenge in clinical development is substantial," says Joseph Reiser, PhD, president and CEO of the biotech company Cytogen. "In fact, it's different from any other field of research."

Outcomes Trials

Clinical oncologists' experimentation and patient demands continue to build momentum for product line extensions, creating a future for targeted therapies that belie the notion that the age of the cancer blockbuster is past.

In 2002, Cytogen plans to begin clinical trials for a human monoclonal antibody targeting a specific prostate cancer marker. it will also test a therapeutic prostate cancer vaccine in collaboration with Progenics later this year. Reiser says, although development occurs after product approval and real-world use, outcomes and Phase IV trials should be planned from the outset:

"You have to begin planning at the time of development, in the regulatory approval stages. Some companies are taking the next step and actually using the outcomes trial as part of the submission, with the intent of having that information on the label as an outcomes endpoint. That's often risky, because if you do it too early, you may not know enough about the drug. Then you have to live with the outcome, whatever it is." On the other hand, Reiser says marketers run the risk of selling the product short if real-world experiences surpass the label claims.

Because communicating preliminary results has its pitfalls, marketers must be cautious about pursuing the "forbidden fruits" of clinical experimentation and peer-to-peer information exchange. A company may want to get potentially life-saving treatments to patients as soon as possible. It may need to satisfy investors or prepare a case for reimbursement, which is understandable, given the tremendous costs associated with targeted treatments. Whatever the motivation, haste makes waste, and balance is crucial to keeping R&D on track, making smart decisions, and keeping sales reps in compliance when detailing physicians.

Respected Sales Force

Oncology sales reps have one major advantage over their peers when they walk into a doctor's office-they get in. Oncologists and oncology nurses rely on their detailers' knowledge in the field, familiarity with traditional therapies, and technical expertise.

"Sales people need to get it absolutely right, because they're asking doctors and nurses to make life-or-death decisions on behalf of their patients to use your product," says Samuel Klein, a senior oncology sales specialist with Novartis Oncology. "It's really important that they know alternative treatments, how the new treatments fit in, and what their advantages are for doctors and patients."

Oncology reps regularly help nurses-often the strongest link to patients-translate complex technical research information into lay language for their patients. In many pharma companies, oncology reps are the most experienced, highest paid, and most independent in the sales force. But the downside to relying on expert employees with that kind of seniority-and compensation-is that companies must invest in ongoing, intensive training and education to keep them that way.

"Oncology sales specialists are extensively trained in products as well as the science behind them," says Michael Becker, Cytogen's vice-president of investor relations and corporate communications, "so they can influence further drug development and promotion, based on feedback they get from the field. A traditional pharmaceutical rep is just not qualified for that involvement."

Opportunity Knocks

Although the global oncology market is expanding, that growth isn't distributed evenly among all types of cancer-and neither is the research funding.

"There's a political correctness for different types of cancer, especially breast and prostate cancers," says Imran Khalifa, industry manager of pharmaceutical research for Frost & Sullivan. "Those diseases are easier to talk about, but they're killing fewer people than lung cancer, for example." She refers to the stigma that people cause their own lung cancer by smoking. Although that may be true in many cases, some lung cancer patients have never smoked.

In the United States, lung cancer kills more people than any other type of cancer. Khalifa cites 2000 research funding estimates from the National Cancer Institute (NCI) showing that it spent $950 on lung cancer research for every US lung cancer death. Compare that figure to research spending for other cancers with much lower-and steadily falling-death rates. In 2000, NCI spent $3,192 on colorectal, $3,667 on prostate, and $8,860 on breast cancer research for every death from those diseases.

The pharmaceutical industry offers better support for efforts to fight the most deadly cancers. According to the Pharmaceutical Research and Manufacturers of America, of the 402 pipeline cancer medicines, 68 are for lung cancer, 59 are for breast, 55 are for colon, and 52 are for skin and prostate cancers.

Given that marketing starts early for competitive companies-sometimes as early as Phase II trials-pharma might benefit from seeking out other areas in which government research is lacking. Such populations may be small and may lack an organized voice but addressing their needs is another way to build new markets that support product growth and extension.

Regulatory approval, market expansion, and even line extensions ultimately create the greatest hurdle of all: getting paid. That issue reaches into every area of research, development, sales, and marketing.

"These drugs are not cheap," says Khalifa. "While chemotherapy might cost $5,000-$6,000 a year, Herceptin can cost up to $16,000 and Gleevec up to $24,000 a year. But it comes down to what the oncologist believes will work in the clinical setting. In that case, price doesn't matter."

Price may not matter to patients or their doctors, but one thing pharma knows for sure is that third-party payers and formulary decision makers care-a lot. Companies have to prove to insurers and government payers-the acknowledged top of the marketing food chain-that their product is worth reimbursement.

In addition to efficacy and safety results, marketers will have to make the most of pharmacoeconomic data. Like FDA, payers and P&T committee members want to see that a new product lengthens life, that it enhances quality of life, and that it slows or stops disease progression. But what they really want to know is the big money question: Will this product keep patients out of the hospital? Early launches of outcomes trials are critical to proving cost-effectiveness and to showing a product's impact over time, which is a risky business in prospective trials.

Considering that many, if not most, of the new cancer diagnoses will be in the growing over-65 population, Medicare guidelines are certain to change-with or without federal legislation for prescription coverage for seniors . Pharma marketers must stay up to date and help clinicians keep up with changes in both private insurer and Medicare claims coding requirements to ensure that cancer breakthroughs don't break their banks.

In the emerging oncology market, success lies in the details-paying close attention to patients' needs is always the top priority. But pharma marketers must remember the many other "customers" linked to their products' success-clinicians, payers, caregivers, and investors-if they want to meet the new challenges while covering their bases.