Second Opinion
Be skeptical about the Herceptin hype
Headshot of Andre Picard

By ANDRE PICARD

Thursday, August 4, 2005 Page A15

The breast cancer drug trastuzumab (better known by its brand name
Herceptin) has had more than its share of good press. It has been
described as "the biggest cancer breakthrough in a decade," "a
life-saving drug" and the "next best thing to a cure."

The laudatory words from some oncologists and patient advocates, along
with extensive media coverage, have placed enormous pressure on public
health plans to fund the treatment. Much of the debate has focused on
the price Genentech Inc. is asking for Herceptin -- between $35,000 and
$45,000, depending on the patient's weight.

Providing Herceptin to a select group of breast cancer patients would
effectively double the cost of treatment and add $150-million a year to
the health-care tab.

But that's a small price to pay for a miracle, right?

Let's leave the discussion of pricing for another day and focus instead
on the other numbers, the ones that tell us just how effective
Herceptin can be in ridding women of breast cancer. (Before going any
further, let's remember that Herceptin is designed only for breast
cancer sufferers who produce too much HER-2 protein -- about one in
four cases.)

The most eye-popping claim is that, for this select group, the drug
cuts the risk of recurrence by half. In clinical trials, women who took
Herceptin along with a standard chemotherapy drug saw their risk of
recurrence fall 52 per cent, compared to women who received chemo
alone. That is an impressive relative risk reduction.

But what matters in the real world is absolute (not relative) risk
reduction. Practically speaking, 15 per cent of women taking Herceptin
and chemo had a recurrence of breast cancer within four years of
diagnosis, compared to 33 per cent of women who took chemo alone. That
is an absolute risk reduction of 18 per cent.

Nobody wants a recurrence, but what matters ultimately is survival.
Herceptin, according to the studies, cut the death rate by one-third.
That sounds impressive, but relative risk reductions always do. In
reality, the difference in the death rate between the Herceptin and
non-Herceptin groups was 2 per cent after three years, and 4 per cent
after four years.

Based on those numbers, can we honestly say that Herceptin is an
essential lifesaving drug?

Like every drug, Herceptin has side effects. In the clinical trials,
the rate of heart failure was 3 per cent higher among women receiving
Herceptin. Is trading breast cancer for heart failure the next best
thing to a cure?

When it comes to drugs, miracles are often short-lived. Tamoxifen was
once the next best thing to a cure for postmenopausal women with breast
cancer. Despite early promise, follow-up studies showed that after five
years of use, the drug actually increased the risk of recurrence, along
with increasing the risk of endometrial cancer.

Then along came letrozole (a drug taken after five years of tamoxifen),
which in studies also cut the risk of recurrence by half. The jury is
still out on whether the medication will increase the risk of
cardiovascular disease.

But at least physicians and women prescribed the earlier drugs have
access to the full data. The most troubling aspect of the Herceptin
story is how little evidence of its effectiveness has been published in
peer-reviewed medical journals.

Clinical trials testing Herceptin for treatment of early-stage breast
cancer were cut short in April after an interim analysis showed "better
than expected" results. Halting research early is controversial at the
best of times. When it has been done in the past -- most famously in
the study declaring hormone replacement therapy to increase the risk of
breast cancer, heart attacks and stroke -- the data were published
immediately.

The Herceptin data have been presented selectively at scientific
conferences, in press releases and news reports. That's bad science.
It's also pretty flimsy evidence on which to make declarations of
miracles, and on which to base tens of millions of dollars in spending.

Women are being advised to take this treatment, and provincial health
plans forced to make decisions on funding, based on inadequate data.

Perhaps it's not fair to single out Herceptin. Every pharma company
dreams of this kind of buzz for its drug. But it is, in the words of
Herceptin's promoters themselves, the dawning of a new era where we
will target disease at its genetic roots, with costly new drugs.

This requires a new era of rigorous, dispassionate analysis that
provides health professionals and patients with timely data on
effectiveness and cost-effectiveness of all drugs.

Herceptin has not met this test.

In the months and years to come, there will be many vaunted
pharmaceutical miracles, many next-best-things-to-a-cure. They must be
kept in perspective. We cannot, in our desperate desire for good news,
suspend our critical faculties.

When it comes to Herceptin, some healthy skepticism is, well, quite
healthy.

apicard(AT)globeandmail.ca