Genentech's Trastuzumab-Dm1 Shows Great Promise in Treating Breast Cancer

Now that the SABC (San Antonio Breast Cancer Conference) is over, and the new year is upon us, what have we learned. Genentech (DNA) just announced data for the most promising oncology product in its pipeline, Trastuzumab-Dm1, or TDM-1. TDM-1 is a next generation treatment for Metastatic Breast Cancer, MBC. Data was presented for 112 patients enrolled in this study, and that 107 of these patients were efficacy evaluable.

At the time of data cut-off for presentation, 8/19/1008, the 112 patients had received a median of 5.0 cycles of T-DM1. Two patients discontinued treatment due to adverse events considered to be possibly related to the study drug. Three of the 112 patients were dose-reduced from 3.6 mg/kg to 3.0 mg/kg for tolerability reasons, and these three patients were still receiving T-DM1 at the time of data cut-off.

The efficacy section of the presentation reported two types of findings: the overall objective response rate (Overall ORR) and the confirmed objective response rate (Confirmed ORR). The Overall ORR includes all complete responses (CRs) and partial responses (PRs) reported, whereas the Confirmed ORR includes only those CRs and PRs that were able to be confirmed with two consecutive scans taken at least 4 weeks apart. (Reasons a response would not be confirmed include that the data cut-off occurred before it could be confirmed, that the patient withdrew from the study before it could be confirmed, and that it was not sustained long enough to be confirmed.)

Among the entire 107 efficacy evaluable patients, the Overall ORR was 39.3% and the Confirmed ORR was 27.1%, with an explanatory note included that these findings include 19 patients who only had one post-baseline tumor assessment (i.e., they had not had the absolute minimum number of assessments needed to confirm a response). Thus, results were also reported for just those patients who had either had at least 6 months of follow-up or had discontinued treatment prior to the data cut-off date. Among these 76 patients, the Overall ORR was 43.4% and the Confirmed ORR was 38.2%.

One of the inclusion criteria for the study is that patients have metastatic breast cancer that is HER2-positive (FISH+ and/or IHC3+). However, among the 86 efficacy evaluable patients where HER2 expression could be confirmed centrally, it was found that only 74.4% were HER2-positive by these criteria. Among the 64 patients confirmed to be HER2-positive, the Overall ORR was 50.0% and the Confirmed ORR was 34.4%.

So what have we learned you ask. Doctors participating in this study have made comments to the effect that this drug, TDM1, needs to be made available immediately for Compassionate Use, for patients with no other treatment options due to stunning efficacy. Virtually every patient in this study has already tried and failed drug regimens which have included Herceptin and Taxotere, and also Tykerb and Xeloda, etc.

The RR, response rate for patients who have tried and failed on Tykerb/Xeloda is very remarkable. Sixty of the efficacy evaluable patients previously were treated with lapatinib. The activity of T-DM1 in these patients was found to be consistent with that in the entire study population (Overall ORR of 38.3%; Confirmed ORR of 21.7%). Trastuzumab-Dm1 is currently being evaluated in two recently started trials. A Phase 2 First-line treatment vs. Taxotere/Herceptin and another potentially Pivotal Phase 2 for 3rd-line treatment for patients who have already tried and failed Tykerb/Xeloda. Genentech could and should apply for approval for 3rd line treatment today. As recently presented data has already shown that TDM1 is quite effective in patients who have failed Tykerb and also has a superior side effect profile.

Again, what have we learned? Genentech, though still in clinical trials with Trastuzumab-Dm1, has the next oncology blockbuster treatment for Metastatic Breast Cancer. And which companies will benefit? Immunogen (IMGN) and Genentech.

Disclosure: Long IMGN

Comments

[tk77mann:]

Fantastic distillation of a complex and important new product test. Thanks for the work and the great summary.

Jan 06 03:58 PM

[carey_jim:]

I have to disagree with the previous comment. Your article was not clear to me.

After plodding through the statistics (and admittedly giving up in frustration) from what I gather, your article confirms what is already clear and it is that the American pharmaceutical industry is completely bankrupt and even immoral in its search for a cure for cancer.

Avastin, the other 'blockbuster' drug from Genentech, costs about $100,000 only to prolong the lives of advanced colon cancer patients by about two months.

Cancer cure rates have remained almost flat for over twenty years.

The profit motive doesn't seem to work well in science.

Einstein wasn't interested in physics for the money.

If Einstein had profited from his discoveries, he and his descendants would have become the richest people in the world (and possibly controlled the entire world.)

My guess is that the drug discovery model will change in the near future and that pharmaceutical companies will fall on, at least compared with the past, hard times.

Just a hunch, of course.

Jan 07 01:04 AM

[on avastin:]

"Overall, patients given Avastin in combination with IFL survived about five months longer and the average time before tumors started regrowing or new tumors appeared was four months longer than patients receiving IFL alone."

www.fda.gov/bbs/topics...

don't know where you got 2 months in colorectal. i think you maybe thinking of lung cancer:
"The median overall survival time for patients in the Avastin plus carboplatin and paclitaxel arm was 12.3 months versus 10.3 months for patients receiving only carboplatin and paclitaxel. "

www.fda.gov/bbs/topics...

and on cost, i think you're using the cost for lung cancer (and maybe breast too) but i think the cost for colorectal is 40k/yr.

On Jan 07 01:04 AM carey_jim wrote:

> I have to disagree with the previous comment. Your article was not
> clear to me.
>
> After plodding through the statistics (and admittedly giving up in
> frustration) from what I gather, your article confirms what is already
> clear and it is that the American pharmaceutical industry is completely
> bankrupt and even immoral in its search for a cure for cancer.<br/>
>
> Avastin, the other 'blockbuster' drug from Genentech, costs about
> $100,000 only to prolong the lives of advanced colon cancer patients
> by about two months.
>
> Cancer cure rates have remained almost flat for over twenty years.
>
>
> The profit motive doesn't seem to work well in science.
>
> Einstein wasn't interested in physics for the money.
>
> If Einstein had profited from his discoveries, he and his descendants
> would have become the richest people in the world (and possibly controlled
> the entire world.)
>
> My guess is that the drug discovery model will change in the near
> future and that pharmaceutical companies will fall on, at least compared
> with the past, hard times.
>
> Just a hunch, of course.

Jan 25 04:02 PM