Article in Nature:
"Emerging targeted agents in metastatic breast cancer"
Abstract
The same article has list of targetted medicine for drugs targetting microenvironment:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T3.html
targetting BC cells in general:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T1.html
targetting BC stem cells:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T2.html
Even a result table for trials which has been completed:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_T4.html
Add up CR+PR+SD divide it with total n to get how good early results are. Unfortunately no progression free survival information on the table. A cursory look at the table tells me the best, by head and legs are palbociclib for ER+ women with (PR+SD = 26 among 34 patients):
| Letrozole ± PD 033299181 | CDK1, CDK6 |
These are very interesting especially if they work for TN women, or could figure out accurate dx test to identify the people who might benefit better:
| Cabozantinib222 | MET, VEGFR2 |
| Dovitinib60 | FGFR1, VEGFR, PDGFRβ, KIT, FLT3 |
| Vorinostat (+ ixabepilone)225 | HDAC | I | 36 | All | All | 2 | 6 | 16 |
| Bosutinib231 | SRC | II | 73 | All | Chemotherapy and/or hormone therapy | 0 | 4 | 24 |
| BKM120217 | PI3K | I | 9 | All | Any | 0 | 1 | 5 |
| BKM120 (+ letrozole)218 | PI3K | I | 51 | ER+/HER2– | AI | 1 | 1 | 13 |
If someone's interested in any of these products, go back to Table 1 or table 2 or table 3, look for the other drugs with similar targets. For example, if you are interested in PD 0332991 (palbociclib), go back to table 1 to look for other CDK targetting compounds. Law of economics would suggest that those drugs will compete well and/or completement well with palbociclib. No guarantee of course.
(Clinical Trial Conjecture I: The Conjecture of Achilles Heel: As soon as someone proved that Achilles has a weakness in his heel, all the arrows from Troy's side is gonna go to the heel until Achilles, the invincible becomes vincible and his heel will look like porcupine.)
Notice also the drugs for whom the results are not so good or even abysmal. Some are not good but has Complete response, that's still interesting. Some may need to pair up with other drugs to perform well. Some may need better diagnostic test to target better. Remember HIV became treatable with a drug cocktail and cancer may be treatable too from a targetted drug cocktail. So not to write any out, but a lot of work needs to be done if so many phase I/II trials are not turning out gold.
There are probably many more drugs whose results are not in yet, or are dropped due to poor results, poor recruitment or for other technical or business reasons. That is the invisible story of breast canc er clinical research. We need more open data, more better designed drug clinical tests for new agents.
Natada in inspire shared these:
http://www.inspire.com/groups/advanced-breast-cancer/discussion/targetd-therapy-clinical-trial-for-breast-cancer-stem-cells-and-mbc/
Nice figure here:
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_F1.html#figure-title
http://www.nature.com/nrclinonc/journal/v10/n4/fig_tab/nrclinonc.2013.29_F2.html
I might as well go into the Clinical Trial Conjecture II:
The Conjecture of Innovation being proportional to iteration speed: The shorter time between lab bench to FDA approval, the faster the disease will get an effective cure. and vice versa.
Comment: neoadjuvant trials like ISPY-2 are going to accelerate the pace of BC innovation
http://clinicaltrials.gov/show/NCT01042379
and the Breast Cancer Clinical Trial Conjecture III:
The Conjecture of Good being the Enemy of the Best: Adjuvant usage of ok drugs for early stage breast cancer may save lives, but they reduce the incentive for actual great drugs that cures late stage breast cancer.
Comment: This is caused by the unique character of breast cancer where early stage breast cancer rarely kills but are extremely common, yet because late stage breast cancer remains a killer, there are vastly more incentive to develop ok drugs for adjuvant use, vs great drugs for late stage bc patients. It seems a lot of pharma would rather repurpose a proven ok cancer drug (developed for a different cancer), spend 10 years and 100s of millions to test its efficacy for breast cancer in adjuvant settings, rather than starting from scratch on new drugs that could potentially cure MBC. You could argue the latter is more risky, or you could argue that the former gets better pay-off in adjuvant use on less risk.
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