Replies to post #115049 on Biotech Values

[tinkershaw]

FWIW for the next 42 patients the bone response rate dropped from 95% to 81%. Still appears good - but given the lack of published historical data... .

Isn't this because this data is utterly unprecedented, and therefore there is no published data. From my understanding bone lesion resolutions are a sort of near "miracle" result, a very outlier that you see every once in a while, and here you have 85% of 63 patients with partial or complete resolution (not broken out), and another 8 with stable disease, no progress, meaning that 62/63 patients either had no progression, and the vast majority of patients had at least a partial reversal in bone scans.

It is unprecedented, and just not something anyone else has seen in any numbers. Here you have 85%.

Please correct me if I'm wrong on this, but I think it is an error to critique the results from lack of published historical data, because there has never been any substance that has ever had results anything near these results.

Tinker

[jq1234]

FWIW for the next 42 patients the bone response rate dropped from 95% to 81%. Still appears good - but given the lack of published historical data... .

It will continue to drop when more data comes in. That's not surprising to me. It didn't drop off sharpy.

PS I haven't yet found good data on ALP (and haven't yet looked for historical data for CTx) on docetaxel - have you seen historical data?

I have seen it, but can't find it now. OGXI may have presented it because their drug OGX011 is in combination with docetaxel compared to docetaxel alone.

[biomaven0]

I haven't yet found good data on ALP

There's this recent publication:

Urol Oncol. 2010 Sep 29. [Epub ahead of print]
Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy.

Sonpavde G, Pond GR, Berry WR, de Wit R, Armstrong AJ, Eisenberger MA, Tannock IF.

U.S. Oncology Research, Inc., Texas Oncology and Baylor College of Medicine, Webster, TX 77598, USA.
Abstract

OBJECTIVES: The association of a change in serum alkaline phosphatase (ALP) with overall survival OS in men with metastatic castration-resistant prostate cancer (CRPC) receiving chemotherapy is unknown. We evaluated the association of changes in ALP within 90 days with OS in men with CRPC and bone metastases treated with docetaxel or mitoxantrone in the TAX327 trial.

MATERIALS AND METHODS: Eligible patients included those with bony metastatic disease, baseline ALP = 120 u/L (upper limit of normal) and =2 post-therapy measurements of ALP available. Survival was estimated using the Kaplan-Meier method and prognostic potential of change in ALP was evaluated using Cox proportional hazards regression. Surrogacy was calculated by the Likelihood Reduction Factor.

RESULTS: 601 patients met the eligibility criteria. By day 90, 159 patients had ALP normalization (<120 u/L) and 442 patients did not normalize. Normalization of ALP remained prognostic for OS after adjusting for PSA decline = 30% by day 90 (HR 0.79, 95% CI = 0.65-0.97, P = 0.022). Increase in ALP remained prognostic for OS when adjusting for PSA increase = 50% by day 90 (HR 1.69, 95% CI = 1.33-2.14, P < 0.001). ALP changes did not meet criteria for surrogacy for OS.

CONCLUSIONS: For men with CRPC, bone metastasis and high baseline ALP receiving docetaxel or mitoxantrone chemotherapy, normalization of ALP by day 90 was predictive of better survival independent of =30% PSA declines. An increase in ALP by day 90 was also predictive of poor survival independent of =50% PSA increase. Given the ready availability of ALP, the validation of our data is warranted.