another example of needing to find the right subgroup to determine drugs efficacy

[Lani]

Dr. Slamon once described how herceptin would never have been approved had they tried it on all breast cancer patients--how the discovery of her2 amplification made it possible to select out those for whom it could prove to be more efficacious than the previous standard of care

I think that is the theme in breast cancer--selecting out the plums, cherries, guavas and kiwis from the apples oranges and pears in the fruit salad and trying to find the cause, best prevention and best treatment for each.

Here again, it turns out that zoledronic acid may be helpful in preventing recurrence but when all breast cancer patients are looked at, the benefit may not be found.

This is far from a slam dunk-- just a suspicion at present that requires proof. But at least they are subdividing to conquer.

Ther Adv Med Oncol. 2011 Nov;3(6):293-301.
Zoledronic acid in breast cancer: latest findings and interpretations.
Gnant M.
Source
Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Abstract
The intravenous nitrogen-containing bisphosphonate zoledronic acid has been shown to block multiple steps in tumor metastasis (e.g. angiogenesis, invasion, adhesion, proliferation) in preclinical and translational studies. Moreover, clinical data from the ABCSG-12 and ZO-FAST trials demonstrate significantly improved disease-free survival with zoledronic acid in the adjuvant breast cancer setting. In contrast to these two trials, recent interim results from the AZURE trial do not show a benefit from adding zoledronic acid to adjuvant therapy in the overall patient population. However, subset analyses of AZURE data show that zoledronic acid significantly improved overall survival in women who were more than 5 years postmenopausal or older than 60 years at baseline. Similarly, subset analyses of the ABCSG-12 trial data demonstrate greater benefits from zoledronic acid treatment in patients who theoretically would have achieved more complete ovarian suppression. These observations, together with the AZURE postmenopausal data, suggest that the endocrine environment may affect the potential anticancer activity of zoledronic acid. Indeed, current data support the possibility that zoledronic acid might be most effective for improving disease-free survival in the adjuvant breast cancer setting in women who are postmenopausal or have endocrine therapy-induced menopause.

PMID: 22084643 [PubMed - in process]

[chrisy]

Thanks Lani,
Yes, you are absolutely right - understanding which patients will benefit is the key. Avastin might turn out, in retrospect, to be one of those as well and if they were able to tease out the responders from the entire pool of BC patients, it could be approved for the appropriate population.

Not to mention, spare patients from costly but ineffective treatments

[alicem]

It makes me wonder if there are any drugs out there that DID get put on the shelf and are covered with cobwebs that could be beneficial to the right subgroup, but we might not ever know.

[Lani]

alicem rest assured I have heard lectures where they are trying just about every drug ever developed/tried against cell lines

Now that things are automated and computerized this goes much faster.

The problem will probably end up being getting the right COMBINATION for the right subtype

[AlaskaAngel]

What it reminds me of that is quite specific to HER2 positive is the most obvious subgroup that still is waiting to be identified.... since the homework has never been done to find out if the group of early stage HER2 positive breast cancer has a BETTER outcome with trastuzumab used alone than with chemotherapy. At present this possibility continues to be just written off entirely.

Just think of how beneficial this could be in terms of people and resources if it ever saw the light of day.

AlaskaAngel