By now, most (but not all) readers know Dendreon's (NASDAQ:DNDN) Provenge's median life extension benefit is 4.1 months. This is the value upon which FDA approval is based, and the one cited - often incorrectly as the average - in the popular literature. There is nothing better available for the (pre-chemo) treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. (Provenge carries an NCCN Category 1 rating in this space versus the NCCN Category 2B rating, the second lowest, for J&Js (NYSE:JNJ) Zytiga.)
Yet, researchers long knew the Provenge trial data were "corrupted" by the fact some patients in the placebo cohorts crossed over and were given a frozen form of Provenge: Frovenge (aka APC8015F). Frovenge was so effective, in fact, that it almost resulted in the failure of the Provenge trials. Specifically, it brought the Kaplan-Meier curves closer together than they might otherwise have been. For that reason, several studies were initiated to remove the data corruption resulted from the crossovers to estimate better the true life extension benefit from Provenge. I addressed this subject here and here.
The first results I discussed are shown in the figure below from the work of Gomella, et al.* discussed in a 2011 ASCO poster presentation. (You can view the 2011 ASCO poster here.**) Figure 3 from that poster shows that the segment of the control arm that did not receive Frovenge had a median survival time of 12.7 months while the segment of the control arm that did receive Frovenge had a median survival time of 23.6 months. This implies that the "true" overall median survival advantage to Provenge should be considerably longer if it is determined in a trial for which the control arm is NOT given Frovenge. In fact, one might reasonably argue, on the basis of these data, that the "true" overall, median survival advantage in treating end stage prostate cancer with Provenge should be something on the order of 12.7 months, or more than one year (25.4-12.7=12.7 months)."
Click to enlarge
In General Poster Session B of 2012 GU, Chadi Nabhan, MD, director of the division of haematology and medical oncology at Advocate Lutheran General Hospital in Park Ridge, Illinois, presented this poster.† From their work, the authors concluded that "[A]djusting for a positive effect of APC8015F [Frovenge] in the control arm resulted in a sipuleucel-T OS treatment benefit in the IMPACT study ranging from 4.1 to 7.8 months." Below are the relevant K-M data from that presentation, which are taken from the poster presentation heretofore only available to conference participants.
According to Nabhan, et al.††, the median OS was 25.8 months for patients in the Provenge arm, 23.8 months for control patients receiving Frovenge (APC8015F), and 11.6 months for control patients who did not receive Frovenge. "These results support a greater treatment effect of sipuleucel-T than reported in the IMPACT study and should be factored into future studies without APC8015F crossover."
Just this week, a new paper has been presented by D.J. George, et al., at the European Society for Medical Oncology (ESMO) meetings. The paper, Number 941P, is entitled IMPACT OF SALVAGE THERAPY WITH APC8015F ON THE OVERALL SURVIVAL (OS) BENEFIT ACHIEVED WITH SIPULEUCEL-T IN THREE PHASE 3 STUDIES OF METASTATIC CASTRATE-RESISTANT PROSTATE CANCER (MCRPC).*** This analysis was performed using the data from three Phase 3 sipuleucel-T trials (D9901, D9902A, IMPACT) in which control patients (pts) were allowed to receive salvage treatment with an autologous product derived from previously frozen cells (APC8015F). According to the abstract, a rank-preserving structural failure time (RPSFT) model was used to estimate control arm OS if treatment with APC8015F had not occurred. This allows estimation of the treatment effect of sipuleucel-T, adjusting for salvage effect.
Here are the results in their entirety: "Median OS from randomization in the three pooled trials was 25.4 months with sipuleucel-T (n = 488) and 21.5 months with control (n = 249). Of the control arm pts, 165 (66.3%) subsequently received APC8015F. Median OS from randomization in the control population was 23.6 months for pts receiving APC8015F and 12.7 months for those who did not. Using the RPSFT model, and assuming APC8015F was as effective as sipuleucel-T, the estimate of median OS for control pts was 17.3 months, representing an 8.1 month median increase in OS with sipuleucel-T. Results from extensions of the RPSFT model, where APC8015F is assumed to have less treatment effect than sipuleucel-T, will be presented."
According to the authors, the estimated median OS benefit for sipuleucel-T was found to be between 3.9 and 8.1 months.
This is consistent with earlier analyses of the same type (see the two above), suggesting a possible greater treatment effect of sipuleucel-T than was reported in the three Phase 3 studies
One concludes the on-label median 4.1 month life extension for Provenge underestimates the overall survival obtainable with this treatment by a factor of up to 2 or 3. In fact, the actual MEDIAN extension benefit resulting from treatment with Provenge may be as high as 12.7 months.
Technical Analysis The Daily chart, courtesy StockChart.com, shows the stock languishing near $4.50. The Relative Strength is neutral, as is the MACD. The Street clearly is awaiting the 3Q12 results, which will be provided by the corporation at the end of October.
The Weekly data tell much the same story as above.
*L. G. Gomella, C. Nabhan, J. B. Whitmore, M. W. Frohlich, D. J. George; The Kimmel Cancer Center at Jefferson, Philadelphia, PA; Advocate Lutheran General Hospital and Oncology Specialists, S. C., Park Ridge, IL; Dendreon Corporation, Seattle, WA; Duke Cancer Institute, Durham, NC
**Reproduced with the permission of Dr. L. G. Gomella, personal communication, November 17, 2011
† Reproduced with the permission of Dr. L. G. Gomella, personal communication, February 17, 2012
†† Chadi Nabhan, Leonard G. Gomella, Todd DeVries, James Boyd Whitmore, Mark Walter Frohlich, Daniel J. George; Advocate Lutheran General Hospital and Oncology Specialists, S.C., Park Ridge, IL; The Kimmel Cancer Center at Jefferson, Philadelphia, PA; Dendreon Corporation, Seattle, WA; Duke Cancer Institute, Durham, NC
*** D.J. George1, L.G. Gomella2, T. Devries3, J.B. Whitmore3, M.W. Frohlich3, C. Nabhan4
1Durham, NC/US, 2Philadelphia, PA/US, 3Seattle, WA/US, 4Park Ridge, IL/US
Additional disclosure: I am long DNDN and will not alter my position within 72 hours of the time of publication of this article. I am not a registered investment advisor and do not provide specific investment advice. The information contained herein is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. It is up to investors to make the correct decision after necessary research. Investing includes risks, including loss of principal.