Janssen’s Zytiga Approved for Earlier Use in Prostate Cancer


“European regulators are allowing earlier use of Janssen’s Zytiga in the treatment pathway for metastatic prostate cancer.

“Zytiga (abiraterone) plus prednisone/prednisolone has been approved to treat newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT).

“The drug is already available in Europe for metastatic castration-resistant prostate cancer (mCRPC) in adults who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated and in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.”

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Abiraterone/ADT Combo Increased Prostate Cancer Survival


“Combined therapy with abiraterone acetate/prednisone plus androgen deprivation therapy (ADT) significantly improved overall survival and radiographic progression-free survival (PFS) among men with metastatic hormone-naive prostate cancer compared with ADT and placebo alone, according to the results of the phase III LATITUDE trial (abstract LBA3) presented at the 2017 ASCO Annual Meeting.

” ‘In my opinion, these findings support the fact that adding abiraterone and prednisone to castration should now be considered the new standard of care for men with newly diagnosed metastatic prostate cancer,’ said researcher Karim Fizazi, MD, PhD, head of the department of cancer medicine at Gustave Roussy, University Paris-Sud, Villejuif, France.”

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Janssen's Zytiga Boosts Survival in Early-Stage Prostate Cancer

“Janssen has announced data from a post-hoc analysis of a Phase III trial showing that Zytiga plus prednisone boosted overall survival (OS) by 11.8 months compared with placebo plus prednisone, in men with early and less aggressive metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy.

“Data presented today at the European Association of Urology (EAU) 2016 Congress in Munich, Germany, demonstrated that in the COU-AA-302 trial, Zytiga (abiraterone acetate) increased OS to 53.6 months versus the 41.8 months achieved by patients treated with prednisone alone. This benefit was shown to be 4.4 greater than that previously reported for the combo in the final analysis of the COU-AA-302 trial in 2014.

“The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in group 1 were in an earlier, less advanced and less symptomatic stage of the disease, while those in group 2 were in a later, more advanced and more symptomatic stage of the disease.”

Hormonal Drugs for Prostate Cancer Increase Risk, Incidence of Cardiovascular Events

“Patients who received hormonal regimens for the treatment of castration-resistant prostate cancer experienced a significant increase in incidence of and relative risk for cardiovascular toxicity, according to results of a meta-analysis.

“Roberto Iacovelli, MD, medical oncologist in the division of urogenital and head and neck tumors at European Institute of Oncology in Milan, and colleagues sought to define the incidence and RR of cardiovascular events in a population of patients treated with new hormonal therapies for metastatic castration-resistant prostate cancer.

“Incidence of all-grade toxicities (grades 1-4) and high-grade toxicities (grade 3-4) served as the primary outcome of the study.

“Iacovelli and colleagues identified six prospective phase 2 or phase 3 studies that included a total of 7,830 patients. Within each study, researchers considered treatment with a novel hormonal agent plus prednisone in the experimental arm (n = 4,520) and placebo plus prednisone (n = 3,310) as the control.”

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.’ ”

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).”

Orteronel Improved Progression Free Survival but Not Overall Survival in mCRPC

“In a phase III trial (ELM-PC 5) reported in the Journal of Clinical Oncology, Fizazi et al found that the addition of the 17,20-lyase inhibitor orteronel to prednisone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel therapy resulted in an overall survival comparison that crossed the prespecified futility boundary at interim analysis. Orteronel treatment was associated with improved radiographic progression-free survival, prostate-specific antigen (PSA) reduction, and time to PSA progression.

“Orteronel targets the effects of CYP17A1, an enzyme important to androgen synthesis that exhibits 17α-hydroxylase and 17,20-lyase activities.

“In the double-blind trial, 1,099 men from 260 centers in 42 countries were randomly assigned  2:1 to receive orteronel at 400 mg plus prednisone at 5 mg twice daily (n = 734) or placebo plus prednisone at 5 mg twice daily (n = 365). The primary endpoint was overall survival…

“The investigators concluded: ‘Our study did not meet the primary end point of [overall survival]. Longer [radiographic progression-free survival] and a higher [≥ 50% PSA reduction] rate with orteronel-prednisone indicate antitumor activity.’ “

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.’ ”

Future of Exelixis Cancer Drug Dims Further With Second Failed Prostate Cancer Study

The gist: A drug called cabozantinib doesn’t do any better than a steroid treatment when it comes to relieving bone pain in men with metastatic castration-resistant prostate cancer. That was the conclusion of a recent clinical trial that tested the drug in volunteer patients. The trial enrolled men who were suffering from moderate to severe pain despite optimized narcotic medication, and whose cancer had worsened after treatment with docetaxel as well as abiraterone and/or enzalutamide. Some of the men in the trial were treated with cabozantinib, and some with the steroid treatment mitoxantrone/prednisone.

“Exelixis (EXEL) announced Monday that treatment with cabozantinib failed to alleviate bone pain compared to a steroid control in men with advanced, metastatic prostate cancer. A negative outcome from the so-called COMET-2 prostate cancer study of cabozantinib was widely expected given the previously announced failure of the COMET-1 study in September. Still, Exelixis shares fell another 10% to $1.49 — an all-time low — on heightened concerns that ongoing cabozantinib studies in kidney and liver cancer may also prove disappointing.

“A few years ago, there was much optimism for cabozantinib based on phase II data showing the drug cleared bone lesions and reduced pain in advanced prostate cancer patients. Cancer that metastasizes, or spreads, to bones is a serious complication leading to fractures, increased pain and eventual death. While many cancer drugs can shrink or eliminate tumors in soft tissue, few if any had ever demonstrated an ability to clear up bone metastases.

“All too often, promising results from phase II studies don’t pan out when larger, confirmatory phase III studies are conducted. That’s exactly what happened to Exelixis. In the COMET-2 study, 15% of prostate cancer patients with moderate to severe bone pain despite use of narcotics responded to treatment with cabozantinib compared to 17% of patients treated with steroids. Clearly, this is not the results Exelixis had in mind three years ago when reporting on the phase II bone lesion/bone pain data in the phase II study.”