Jevtana Delays Disease Progression, Prolongs Survival in Men with mCRPC, Phase 4 Trial Shows

The chemotherapy agent Jevtana (cabazitaxel) is better than a second course of androgen receptor inhibitors at delaying disease progression and prolonging survival among men with metastatic castration-resistant prostate cancer (mCRPC), a Phase 4 trial shows. All of the participants had seen their disease progress while previously receiving androgen receptor-targeted agent therapy and docetaxel.

The trial’s findings were shared in a late-breaking presentation, titled “CARD: Randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC),” at the European Society for Medical Oncology (ESMO) 2019 Congress, held Sept. 27 to Oct. 1 in Barcelona, Spain. The results also were simultaneously published in The New England Journal of Medicine.

Jevtana is a chemotherapy agent marketed by Sanofi Genzyme now used to treat men with advanced forms of prostate cancer.

The effects of Jevtana in combination with prednisone in delaying disease progression and prolonging the life of men with mCRPC are currently being investigated in the Sanofi-sponsored, open-label, randomized, CARD Phase 4 trial (NCT02485691).

CARD has enrolled a total of 255 men with mCRPC whose disease progressed after receiving androgen receptor-targeted agent therapy — Zytiga (abiraterone) or Xtandi (enzalutamide) — and docetaxel. The trial spans 62 clinical sites spread across 13 European countries.

Participants were randomly assigned to receive either Jevtana administered intravenously every three weeks or a different androgen receptor-targeted agent. Those who had previously been treated with Xtandi now received Zytiga plus prednisone, while those who had previously been treated with Zytiga were now given Xtandi.

Patients receiving Jevtana also were given granulocyte colony-stimulating factor (G-CSF), a medication that stimulates the production of some white blood cells that are often depleted by chemotherapy. This reduced Jevtana’s side effects.

The trial’s primary endpoint was to evaluate the time patients lived until disease progression or death due to any cause. Disease progression was characterized as the appearance of new metastatic bone lesions or enlargement of existing metastatic bone lesions visible in radiographs. Death due to any cause is a measure called radiographic progression free survival (rPFS).

Secondary endpoints included overall survival and treatment safety assessments.

After a median follow-up period of 9.2 months, 80.2% of the participants receiving Zytiga or Xtandi showed signs of radiographic disease progression or had passed away. Meanwhile, 73.6% of those receiving Jevtana had the same outcome.

Overall, Jevtana extended the time patients lived without signs of radiographic disease progression or death from 3.7 to 8.0 months, cutting the risk of radiographic disease worsening or death by 46%.

Jevtana also increased patients’ overall survival (13.6 months vs. 11.0 months), lowering the risk of death from any cause by 36%, and the time they lived until showing any sign of disease progression or dying (4.4 versus 2.7 months), compared with androgen receptor-targeted agents.

The researchers also assessed the effect of the therapies on prostate-specific antigen (PSA) levels, a marker of prostate cancer. More patients on Jevtana (35.7%) experienced a reduction by 50% or more in their PSA levels, compared with those on androgen receptor targeted treatments (11.5%), the results showed. Likewise, Jevtana increased the percentage of men whose tumors responded to treatment (36.5% versus 11.5%).

The incidence of severe (grade 3), life-threatening (grade 4), or fatal (grade 5) adverse events was similar in both groups. It was 56.3% for those treated with Jevtana, and 52.4% for those treated with androgen receptor-targeted agents.

The most frequent severe adverse events seen in men from both groups included kidney disease, infections, muscle pain or discomfort, heart disease, spinal cord or nerve disorders, fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

However, fewer patients on Jevtana (5.6%) died from an adverse event during the study, compared with those on Zytiga or Xtandi (11.3%). No new safety concerns associated with treatment were reported during the study.

“In this study, treatment with Jevtana significantly improved radiographic progression free survival and overall survival compared with enzalutamide or abiraterone,” Ronald de Wit from Erasmus MC University Hospital in Rotterdam, the Netherlands, and lead investigator of the CARD trial, said in a press release.

“These  results are exciting as they have the potential to impact treatment guidelines for metastatic prostate cancer and current clinical practice,” he added.