The media are abuzz today about the FDA's approval of the new breast cancer drug Tykerb, also known by its generic name, lapatinib.
Reporters are asking how important this new targeted therapy really is and what its impact will be on the treatment of women with breast cancer.
The answers to these questions are fairly straightforward, but the impact over time is a bit more uncertain.
Breast cancer is not one single disease.
When breast cancer is diagnosed, doctors examine the cancer specimen for several different markers that give us clues as to how the cancer will behave -- and what treatments may be helpful in preventing its recurrence. These tests also provide clues to what treatments may be most effective if the breast cancer relapses.
For many years, we have measured hormone receptors (estrogen and progesterone) in the breast cancer tissue, and more recently doctors have looked for another genetic marker called HER2.
When this HER2 marker is present in the cancer tissue (as is the case in approximately 20 percent of the estimated 178,480 invasive breast cancers that will be diagnosed in women in the United States in 2007), it signals a cancer that is usually more aggressive than the typical breast cancer. It also usually occurs in a younger population.
Herceptin, also known by its generic name, trastuzumab, is a drug that targeted this abnormality in breast cancer tissue. When it was first approved by the Food and Drug Administration in 1998, it represented a significant step forward in the treatment of advanced breast cancer in women who had this particular genetic marker.
Trastuzumab improved response rates and lengthened survivals for many women who had found themselves in a grim situation. It wasn't a cure, but it was a major step forward.
It represented not only an effective cancer therapy but also proof that targeted therapies could be very helpful in the treatment of a variety of cancers.
More recently, in 2005, research was presented at a major cancer meeting and then published in the New England Journal of Medicine that trastuzumab was very effective when used in the adjuvant treatment -- the therapy that follows primary treatments like surgery and radiation -- when breast cancer patients were HER2 positive.
These studies demonstrated that trastuzumab, as part of a regimen of adjuvant chemotherapy, decreased recurrences and decreased deaths in women with breast cancer who were HER2 positive at the time of initial diagnosis.
The impact of these reports was dramatic. They literally changed the standard of care for breast cancer treatment overnight in the United States and elsewhere.
But for those women who could not tolerate trastuzumab, or whose disease progressed after taking this intravenous drug, there have been few effective options and certainly no new targeted therapies that honed in on the particular genetic marker in question.
That's where lapatinib fits in, and that is why there is so much excitement.
Lapatinib is a drug that is taken orally, and it works in the same women who are candidates for trastuzumab -- namely, those who are HER2 positive.
In a study and editorial reported in the New England Journal of Medicine in December 2006, researchers reported the results of a clinical trial in which women with breast cancer who were HER2 positive and had failed treatment with intensive chemotherapy and trastuzumab were randomly assigned to be treated either with another chemotherapy drug as a single agent, or with the same chemotherapy drug along with the addition of lapatinib.
The results in this study of 324 women showed that, in the women who had received chemotherapy plus lapatinib, the time it took for the cancer to resume its advance after starting the new treatment was 8.4 months on average.
For the women who received just the chemotherapy without lapatinib, the time to disease progression was 4.4 months.
In other words, the women who received the additional new targeted therapy had their disease remain at least stable for almost twice as long as the women who received only chemotherapy.
Unfortunately -- and this is an important observation -- the overall survival for both groups, whether treated with chemotherapy alone or chemotherapy with the addition of the targeted therapy, was equivalent.
So what does this mean? Is this really a great new breakthrough in the treatment of breast cancer? Where does it fit today in the treatment of breast cancer, and what are lapatinib's future prospects?
Today, the answers to these questions are fairly straightforward. But interestingly, the answers may be more difficult as time goes on and we learn more about the benefits, risks and effectiveness of both lapatinib and trastuzumab.
First, is this a great breakthrough?
Yes, and no.
Yes, it is a significant step forward because it once again demonstrates the promise of targeted therapies, where we take our understanding of how cancer cells work and apply that knowledge to new drug development.
Yes, because we now have a new drug that offers promise and hope to women who have a more aggressive form of breast cancer, where until very recently we had little to offer. Now, we have two drugs that are effective in treating this particular form of the disease.
Will this change the way we treat breast cancer patients today?
For the most part, no. Women who have surgery or recurrence of their disease will still be tested for HER2. If they are positive for the marker and are candidates for trastuzumab, they will still most likely (and appropriately) receive trastuzumab as their first-line choice of treatment.
I do not see lapatinib being used today in the adjuvant therapy of breast cancer, except perhaps in those women who cannot tolerate trastuzumab.
We need to remember that lapatinib was tested only in women with advanced and progressing breast cancer where other treatments -- including chemotherapy and trastuzumab -- had been tried and failed. So, these were the types of situations in which any response was welcome news, even if it didn't prolong survival.
Over time, I have no doubt that studies will be done to look at lapatinib's effectiveness earlier in the treatment of breast cancer, such as at the time of first recurrence and possibly even in a head-to-head comparison with trastuzumab.
There may even come a time when both drugs will be used together to find out if the combination is more effective than either drug alone.
But for now, lapatinib is going to be used to treat women with breast cancer that can no longer be effectively treated with trastuzumab, or when a woman cannot tolerate trastuzumab.
Advances in the treatment of cancer rarely come in big, giant steps. They come in a series of smaller advances that, when grouped together over time, result in significant progress.
That has been the case with the treatment of colorectal cancer and breast cancer, and this pending announcement regarding the possible approval of lapatinib will have a similar impact.
But that does not diminish the fact that we are in the midst of a revolution in which we are rapidly developing and using targeted therapies for targeted cancers.
The era of truly personalized medicine in the treatment of cancer is just beginning.
Dr. Len Lichtenfeld is deputy chief medical officer for the American Cancer Society. You can view the full blog by clicking here.