GSK Announces Trial Results - Tykerb - Lapatinip

[Joe]

GlaxoSmithKline receives positive data and halts enrolment in Phase III trial of Tykerb® (Lapatinib) in advanced breast cancer





First Regulatory Filings now Planned for 2nd Half of 2006







Based on the unanimous recommendation of an Independent Data Monitoring Committee (IDMC), GlaxoSmithKline (GSK) announced today that it has halted enrolment in its Phase III clinical trial evaluating the combination of Tykerb (lapatinib ditosylate) and capecitabine (Xeloda®) versus capecitabine alone. The trial evaluated women with refractory advanced or metastatic breast cancer who have documented ErbB2 (HER2) overexpression and whose disease progressed following treatment with trastuzumab (Herceptinâ) as well as other cancer therapies. A pre-planned interim analysis of 321 patients in the study yielded statistically significant results, exceeding the primary endpoint.



According to the study protocol, the pre-planned interim analysis was reviewed by the IDMC, which is comprised of medical oncology experts and a statistician. The IDMC unanimously recommended halting enrolment in the study because it exceeded its primary endpoint of time to disease progression, or TTP, for women receiving the combination of Tykerb and capecitabine. The IDMC made their recommendation based on pre-specified stopping rules outlined in their charter. All women currently enrolled in the trial will continue to be followed and those who are receiving capecitabine alone will be offered the option of switching to the combination therapy of capecitabine and Tykerb in consultation with their physician.



“We are extremely encouraged by these data which suggest that Tykerb may offer significant benefit as an oral medication in combination with chemotherapy for patients with advanced or metastatic ErbB2 positive breast cancer, and whose disease has progressed on previous treatment regimens, including Herceptin,” said Paolo Paoletti, M.D., Senior Vice President of the Oncology Medicine Development Center, at GSK. “On the basis of this and other data we now plan to file in the USand Europeduring the second half of 2006.”


The Phase III trial (EGF100151) is an international, multicentre, randomised, open-label study to evaluate and compare TTP in patients with documented ErbB2 (HER2) overexpressing refractory advanced or metastatic breast cancer treated with Tykerb in combination with capecitabine versus capecitabine alone. The primary endpoint of the study was to detect a 50 percent increase in TTP in the combination arm compared with the capecitabine alone arm. 392 patients have been enrolled in the study of which 321 were included in the analysis (160 in the combination arm and 161 in the monotherapy arm). The most common drug-related adverse events in the combination arm of the study were diarrhea and nausea.



Tykerb is an experimental drug that does not have regulatory approval in any country for any use outside of clinical trials.



About Metastatic Breast Cancer

The World Health Organization reports that just over one million cases of breast cancer are diagnosed annually. Breast cancer is the most common non-cutaneous malignancy in women and one of the leading causes of cancer death.



Approximately 10-20 percent of newly diagnosed breast cancer patients have locally advanced and/or metastatic disease; 20 to 85 percent of patients (depending on initial stage, tumor biology, and treatment strategy) diagnosed with early breast cancer will develop recurrent and/or metastatic disease.1 The median survival time for women treated for metastatic breast cancer is two years.2



About Tykerb

Tykerb, a small molecule that is administered orally, inhibits the tyrosine kinase components of ErbB1 and ErbB2 receptors. Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple processes involved in tumor progression, invasion, and metastasis. Overexpression of these receptors has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival. GSK is using advanced technologies, including pharmacogenetics, to better define patient populations that may respond to Tykerb.

Tykerb is being developed by GSK as an orally administered therapy for breast cancer and other solid tumors.

[RhondaH]

Our prognosis is looking brighter every day

Rhonda

[Shell]

Joe-


That is the clinical trial in which I was participating - hurray! I hope to get Tykerb/lapatinib as soon as it is available. (I was in the control arm with xeloda alone).

And it is impressive yet again that this is the first site where I learned the news. Thanks to all for sharing your knowledge - it means so much, especially with the potential of a new drug for me and for us!!

Kind regards,
Shell

[Lee]

Thanks for posting this - gives me lots of hope!

This just keeps getting better and better for us.

One day I pray they will cure this beast.

Thanks Joe
Randi

[AlaskaAngel]

I'm very, very happy to hear it, and for all those who will benefit from this option.

Still, given the history of being one of a very large group of patients who were never studied to define the benefits of Herceptin, I have to wonder about whether that will continue to be our fate over and over with each new drug that is developed.

"GSK is using advanced technologies, including pharmacogenetics, to better define patient populations that may respond to Tykerb."

AlaskaAngel

[Julie2]

Terrific news, salute to all those who participated in the clinical trial.

Julie

[lexigirl]

Joe,

Thank you so much for posting the news. It really makes me feel hopeful on my dreary rainy day!

Lexi

[madubois63]

This made me cry!!! Thanks for posting!!!

[Cathya]

Thank you so much for posting this information. I have been worried and it really helps to know that great things are happening which will give us hope. I can live with pain, no hair, throwing up, swelling, even fear....but I can't live without hope.

Best regards,

Cathya

Thanks for the news! I heard this was coming. Isn't this great?

[RobinP]

Whoops forgot to log in above.

[karenann]

Woohoo!!!! Great news.

Hugs,

Karen

[Lolly]

Yes, great news! My onc and I talked about Tykerb earlier this spring, and how wonderful it's going to be seeing drugs like this start coming out for all the other cancers.

<3 Lolly

doesn't anyone else here think these trials with only 321 people are not a true representation of the drug? the pharmacutical company would love to see this fast tracked but come on....321 people is not a true slice of the pie. they did the same thing with herceptin and now this drug for all the people that herceptin doesn't work on. this make s me skeptical. even if it works for 1 person, i'm thrilled for that person. but these tiny little studies certainly give false hope for the huge population that by the very posting on this web site, we know that each tumor has so many different components to it. different in each person. they need a much larger piece of the pie before throwing out another miracle drug.

[Shell]

isn't the bigger issue why we have so few patients participating in clinical trials? i was in this clinical trial, and i had to do the initial research on it, ask my onc about it, locate a hospital over 100 miles from my home (and i live near phila!) and take all of the efforts to be included in it.

the point well taken is that while 30% or so of women have her2neu that may benefit on herceptin, those of us who had herceptin but progressed on it are as eager and entitled to have another drug researched as those on herceptin. and recall too the studies being done on it related to bc brain mets... although we are a small segment of the bc pie, i want my slice of a cure as much as the next person...

regards,
Shell

[Joe]

Actually the results were similar in the phase II trials with only 41 subjects being tested.

Last September we attended an interesting presentation by Dr. Mark Pegram of the Jonnson Comprehensive Cancer Center who is a leading investigator in many clinical trials. He explained the clinical trial process in great detail. There is more that meets the eye. The test criteria proposed by the manufacturer can number hundreds of pages. The FDA will study the proposal for several months, may require changes or additions before they give their approval to start the trial. Basicly the entire process is controlled by the FDA and there can be no deviation by the investigator.

Apparently the FDA considered 331 patients sufficient for this particular trial.

Regards
Joe