Tasquinimod Development in mCRPC Halted After Phase III Study Falls Short

“Topline results announced today from the phase III Swedish trial 10TASQ10 demonstrated that tasquinimod failed to extend overall survival (OS) in men with metastatic castrate-resistant prostate cancer (mCRPC; HR=1.09; CI 95%, 0.94-1.28). The findings prompted the manufacturers, Active Biotech and Ipsen, to discontinue all studies in prostate cancer involving the agent, according to a joint statement.

“Previously, OncLive reported on the results of a phase II trial that showed a prolonged progression-free survival (PFS) and OS with tasquinimod in certain men with mCRPC.1 Men in that trial were followed for a median of 37 months. At the time, researchers suggested the agent may provide a survival advantage in this setting, particularly among men with skeletal metastases.

“ ‘The outcome of the 10TASQ10 study is a major disappointment based on the promising phase II results,’ Tomas Leanderson, president and chief executive officer of Active Biotech said in a statement. ‘However, the data at hand are unambiguous and cannot motivate further development of tasquinimod in this patient population.’

“Although the antiangiogenic agent did not improve OS, it did reduce the risk of radiographic cancer progression or death compared to placebo (HR = 0.69; 95% CI, 0.60-0.80). Full results will be presented at an upcoming scientific conference.”


A New Prognostic Test for Patients with Metastatic CRPC

“In an analysis reported in the Journal of Clinical Oncology, Scher et al found that circulating tumor cell count and LDH level served as an individual-level surrogate for survival among patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate (Zytiga) plus prednisone vs prednisone in the phase III COU-AA-301 trial.

“The double-blind COU-AA-301 trial included 1,195 patients previously treated with paclitaxel. The current analysis includes 711 patients (484 in the abiraterone-prednisone group, 227 in the prednisone group) with available 12-week biomarker data. Biomarker analysis was a secondary objective of the trial.

“The combination of circulating tumor cell count and LDH level at 12 weeks was shown to satisfy the four Prentice criteria for individual-level surrogacy (ie, treatment must have a significant effect on the clinical endpoint and a significant effect on the biomarker, the biomarker must have a significant impact on the endpoint, and the full effect of treatment on the endpoint must be captured by the biomarker)…

“The investigators concluded: ‘A biomarker panel containing [circulating tumor cell] number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic [castration-resistant prostate cancer]. Additional trials are ongoing to validate the findings.’ ”


Enzalutamide Extends PFS in Castration-Resistant Prostate Cancer

“Patients with castration-resistant prostate cancer treated with enzalutamide demonstrated significantly longer PFS than those treated with bicalutamide, according to topline results of the phase 2 STRIVE trial released by Astellas.

“The trial included 396 patients with castration-resistant prostate cancer. About two-thirds of the patients (n = 257; 64.8%) had metastatic disease. The other 139 patients had nonmetastatic disease that progressed after surgical castration or treatment with a luteinizing hormone-releasing hormone analogue therapy.

“Researchers randomly assigned patients to 160 mg once-daily enzalutamide (Xtandi; Astellas, Medivation) — an androgen receptor antagonist — or 50 mg once-daily bicalutamide, an oral non-steroidal antiandrogen. PFS served as the primary endpoint.

“Patients assigned enzalutamide demonstrated a significant improvement in median PFS (19.4 months vs. 5.7 months; HR = 0.24; 95% CI, 0.18-0.32), according to a press release issued by Astellas. Median time on treatment also was longer in the enzalutamide group (14.7 months vs. 8.4 months).”


Lenalidomide Combination Fails to Improve Survival in Castration-Resistant Prostate Cancer

“The addition of lenalidomide to docetaxel and prednisone was associated with a significantly greater mortality rate in patients with metastatic castration-resistant prostate cancer, according to phase 3 study results.

“Daniel P. Petrylak, MD,professor of oncology and urology at Yale School of Medicine and a HemOnc Today Editorial Board member, and colleagues evaluated data from 1,046 chemotherapy-naive patients with metastatic castration-resistant prostate cancer.

“Researchers randomly assigned 525 patients to receive docetaxel and prednisone plus lenalidomide (Revlimid, Celgene). The other 521 patients received docetaxel and prednisone plus placebo.

“After a median follow-up of 8 months, 221 patients had died (lenalidomide arm, n = 129; placebo arm, n = 92). The number of deaths that occurred during treatment or within 28 days of receiving the final dose was similar in both groups (lenalidomide, n = 18; placebo, n = 13).”


Video: Dr. Higano on Radium-223 for mCRPC

“Celestia S. Higano, MD, FACP, professor of medicine and urology, University of Washington, discusses radium-223 chloride and its efficacy for patients with metastatic castration-resistant prostate cancer (mCRPC).

“Higano says radium-223 (Xofigo), a radium isotope recently approved by the FDA to treat mCRPC, is unique from other therapies in cancer overall. Results from a phase III study showed that patients who received radium-223 had higher overall survival (OS) compared to patients who did not receive the therapy.

“Radium-223 can also benefit patients who may have skeletal metastases, fractures, or require external beam radiation, Higano says.”

Click through to watch the video.


Progenics Pharmaceuticals Presents Positive Phase 2 Data for PSMA ADC in Metastatic Castration-Resistant Prostate Cancer

“Progenics Pharmaceuticals, Inc., (Nasdaq:PGNX) today announced the presentation of the full results from its Phase 2 clinical study of PSMA ADC in patients with metastatic castration-resistant prostate cancer (mCRPC), including new data from the recently completed chemo-naïve cohort. The data was presented in a poster session and was also selected for inclusion in the ASCO GU Audio Poster Tour at the American Society of Clinical Oncology Genitourinary Cancers (ASCO GU) Symposium, taking place from February 26 – 28, 2015 in Orlando, Florida.

” ‘The full data from this trial provides compelling evidence of the anti-cancer properties of PSMA ADC, with both the surrogate biomarker and radiological data suggesting a meaningful clinical benefit in progressive metastatic castration-resistant prostate cancer,’ stated Daniel Petrylak, M.D., Professor of Medical Oncology at Yale Cancer Center, Clinical Research Program Leader for the Prostate and Urologic Cancers Program at Smilow Cancer Hospital at Yale-New Haven, and lead investigator on the trial.

” ‘Although advances in androgen deprivation therapy, or ADT, have provided great benefit to prostate cancer patients, treatment options when ADT fails remain limited, which is why the results for PSMA ADC in this patient population are so encouraging. We observed shrinkage of patients’ tumors, the conversion of unfavorable levels of circulating tumor cells to favorable levels and the reduction in patients’ PSA scores, all of which provide strong evidence of PSMA ADC anti-tumor activity,’ said Mark Baker, CEO of Progenics.”


AR-V7 Biomarker Could Guide Treatment in mCRPC Patients

“In men with metastatic castration-resistant prostate cancer (mCRPC), the presence of androgen receptor V7 (AR-V7) in circulating tumor cells did not significantly affect response to treatment with taxane therapy, according to the results of a small prospective study (Abstract 138) presented at a press conference held in advance of the 2015 ASCO Genitourinary Cancers Symposium.

“In fact, researchers led by Emmanuel Antonarakis, MD, assistant professor of oncology and urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, found that men who had AR-V7 detected in circulating tumor cells (AR-V7–positive) may retain their sensitivity to taxane-based treatment.

“An earlier study by Antonarakis and colleagues found that AR-V7–positive mCRPC patients treated with either enzalutamide or abiraterone fared worse than AR-V7–negative patients.

“AR-V7 is a truncated form of the androgen receptor that is detected in about one-third of patients with CRPC. AR-V7 lacks the ligand-binding domain of the androgen receptor, the target of enzalutamide and abiraterone.”


Docetaxel Was Widely Used to Treat Metastatic Prostate Cancer before Conclusive Evidence Showed Its Superiority

The gist: The drug docetaxel was widely used to treat patients with metastatic prostate cancer before phase III clinical trials showed it was better than standard treatment. This is significant for a few reasons. First, it shows that many doctors are willing to prescribe promising drugs “off-label,” before the U.S. Food and Drug Administration (FDA) has approved them  for treating certain conditions. It also shows that a drug that is used for one type of cancer is more likely to be prescribed off-label for other types of cancer. Some are concerned that off-label prescriptions undermine the clinical trial process and put some patients at risk by giving them drugs that may not turn out to be better.

‘Docetaxel was being widely used by patients with metastatic prostate cancer before phase III evidence that it was more effective than standard-of-care for patients with castration-resistant prostate cancer, according to an analysis of Medicare claims from before and after the trial results and approval of docetaxel by the U.S. Food and Drug Administration. The uptake of new treatments, or diffusion, “prior to definitive evidence indicates the prevalence of off-label chemotherapy use,” wrote Unger et al in the Journal of the National Cancer Institute

“Rapid and widespread use of docetaxel was not observed among all study participants receiving chemotherapy for metastatic prostate cancer. Statistically significant docetaxel uptake (P < .01) was seen in patients older than 65 years of age, blacks, patients in lower income areas, and those who experienced poverty. This observation ‘presents opportunities to improve the uptake of proven new therapies in subpopulations,’ the authors wrote, adding that direct-to-consumer advertising ‘could be a useful tool.’

Another potential method cited for encouraging more rapid adoption of new treatments was ‘enhancing communication channels among physicians, especially between key opinion leaders and their colleagues,’ the authors noted. ‘One factor that has been repeatedly identified to increase adoption rates is attendance at scientific symposia, which serve as forums for disseminating information about new treatments.’ ”


Zytiga with Prednisone Improves Survival in Castration-Resistant Prostate Cancer Patients

The gist: Adding the drug abiraterone acetate (Zytiga) to treatment with prednisone helps patients with castration-resistant prostate cancer (CRPC) live longer. The treatment was tested in patients in a clinical trial. Patients in the trial were treated between April 2009 and June 2010. The treatment appeared to lengthen the amount of time that patients lived without their disease worsening. In 2011, these promising results convinced the U.S. Food and Drug Administration (FDA) to approve Zytiga for treating metastatic castration-resistant prostate cancer patients who had not yet received chemotherapy. Now, in final analysis of data from the trial, researchers have shown that Zytiga lengthens life for these patients.

“In the final analysis of overall survival in the COU-AA-302 trial, reported in The Lancet Oncology by Ryan et al, the addition of abiraterone acetate (Zytiga) to prednisone significantly prolonged survival in chemotherapy-naive patients with castration-resistant prostate cancer. Abiraterone had been approved for use in this setting on the basis of improved radiographic progression-free survival in COU-AA-302.

“In this double-blind trial, 1,088 asymptomatic or mildly symptomatic patients were randomly assigned between April 2009 and June 2010 to receive abiraterone at 1,000 mg once daily plus prednisone at 5 mg twice daily (n = 546) or prednisone plus placebo (n = 542). The coprimary endpoints were radiographic progression-free survival and overall survival…

“The investigators concluded: ‘In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.’ ”