Wall Street Journal's "take" on Tykerb (lapatinib) news/presentation at ASCO

[Lani]

Glaxo Touts Experimental Tykerb
As Effective Breast-Cancer Treament
By JEANNE WHALEN
June 3, 2006 8:08 a.m.
An experimental drug has proved effective at treating an aggressive form of breast cancer in patients who aren't responding to the widely used drug Herceptin, giving hope to women with otherwise limited treatment options, said drug maker GlaxoSmithKline PLC, presenting the results Saturday at the American Society of Clinical Oncology meeting in Atlanta.

When taken with a standard chemotherapy treatment in a clinical study, the new drug, Tykerb nearly doubled the time to 8.5 months before the average patient's breast cancer got worse compared to chemotherapy alone. No significant extra side effects were experienced by patients taking Tykerb and chemotherapy, compared to those taking just chemotherapy.

The results, presented Saturday at the important American Society of Clinical Oncology meeting, could eventually give doctors a new way to treat tumors that produce an excess amount of a protein called HER-2. Such tumors account for 20% to 25% of all breast-cancer cases and tend to grow more aggressively than other types of breast cancer.

Tykerb is not yet approved for sale in any country. GlaxoSmithKline plans to submit the drug for regulatory approval in the U.S. and Europe by the end of this year.

For several years, Herceptin has been the standard treatment for metastatic HER-2 positive breast cancer. The drug is remarkably effective at shrinking tumors and extending the lives of many HER-2 positive patients, but some women find that their cancers start growing again after a period of time taking the drug. Herceptin use is also associated with cardiovascular side effects in some patients.

Tykerb treats the same type of tumor in a different way. In a randomized trial that ended in April of this year, 392 patients whose HER-2 positive cancer had started growing again after treatment with Herceptin and chemotherapy were split into two groups. One was given a combination of Tykerb and the chemotherapy Xeloda, and the other Xeloda on its own. In the Tykerb plus Xeloda group, the median time of stability patients experienced before their cancer got worse was 8.5 months, compared to 4.5 months for those taking just Xeloda. Glaxo said both groups experienced a similar level of adverse side effects, including some cases of diarrhoea, rash and hand-foot syndrome, a common side effect of chemotherapy that causes swelling and blistering in the hands and feet.

"These results indicate that [Tykerb] can provide a needed alternative when [Herceptin] no longer appears to be helping to control the disease," Charles Geyer, the oncologist who led the clinical trial, said in a statement Glaxo released to announce the results. Dr. Geyer is director of breast medical oncology at Allegheny General Hospital in Pittsburgh, Penn.

Importantly, no patients in the trial developed symptoms of heart failure, which is a side effect sometimes associated with Herceptin, Dr. Geyer said. In the Tykerb group, 2.5% of patients experienced a decrease of 20% or more in their left ventricular ejection fraction, a measure of the strength of the heart. This compared to 1% of patients taking just chemotherapy.

The ability to claim that Tykerb is associated with fewer cardiac side effects could eventually give Glaxo a marketing advantage over Herceptin, which is sold by Genentech Inc. and Roche Holding AG. Herceptin sales are forecast to rise to $1 billion this year.

Paolo Paoletti, head of oncology medicine development at Glaxo, said the company and various breast-cancer groups were studying Tykerb in a number of breast-cancer trials, including as an earlier-stage treatment, in an attempt to find all the drug's potential applications. These tests will show whether Tykerb can ever compete directly with Herceptin, he said.

Tykerb's possible activity in fighting brain metastases -- or breast cancer that has spread to the brain -- could give the drug an important advantage if Tykerb is approved for sale. About one-third of women with advanced Her-2 positive breast cancer find that the cancer spreads to their brain. Studies have shown that Herceptin does not appear to be effective at reducing this risk. In the Tykerb study, only 4 patients receiving Tykerb plus Xeloda experienced a relapse of cancer in the brain, compared to 11 patients in the chemotherapy-only arm. "While the results are not statistically conclusive, they do suggest that Tykerb may be effective in reducing the risk for the occurrence of brain metastases," Dr. Geyer said.

Glaxo officials believe Tykerb may have this effect because it is an oral, small-molecule drug that is able to cross the blood-brain barrier, the membrane that controls the passage of substances from the blood into the brain. Herceptin, a large-molecule drug given by infusion, does not cross the blood-brain barrier.

Tykerb, also known by the generic name lapatinib, works by inhibiting two cell receptors that regulate tumor-cell growth. Glaxo, which is attempting to dramatically boost its sales of oncology drugs, has high hopes for Tykerb and is also testing it against head and neck, gastric and renal cancer.

The breast-cancer trial that Dr. Geyer led was ended ahead of schedule because patients taking Tykerb were responding so well. An independent monitoring committee that was overseeing the trial decided that for ethical reasons, all of the patients in the trial should be offered Tykerb treatment, the company said.

[RhondaH]

"Paolo Paoletti, head of oncology medicine development at Glaxo, said the company and various breast-cancer groups were studying Tykerb in a number of breast-cancer trials, including as an earlier-stage treatment, in an attempt to find all the drug's potential applications. These tests will show whether Tykerb can ever compete directly with Herceptin, he said."?

Rhonda

[LovingDaughter]

This is great news! I just hate all of the waiting games, though, and the fact that they don't know whether this drug would be effective in combating early breast cancer. It makes me sick to think that there is a drug out there that might help my mom, but that she won't be taking it right now because of the uncertainty.

I guess that's just science for you!

[RobinP]

....and then there is off the label use, when available, for late adjuvant use. But, adjuvant tx has to end somewhere....