“Prostate cancer drug could provide two precious extra months of life to men in advanced stages of the disease,” reported the Daily Mail .
This news story covered a clinical trial that compared a new drug, cabazitaxel, with the existing treatment, mitoxantrone, in men who had advanced prostate cancer that had spread despite chemotherapy and hormone treatment. Mitoxantrone is used in certain advanced cancers, particularly breast cancer, which have spread to other parts of the body. Past trials have shown that it can improve quality of life and it may be used as part of palliative care.
The study found that compared with mitoxantrone, cabazitaxel extended the time before the disease progressed by 1.4 months on average and improved overall survival by 2.3 months. This year, cabazitaxel has been approved by the American Food and Drug Administration for this use, but it has not yet received its European licence, which is necessary for it to be prescribed in the UK.
Where did the story come from?
The study was carried out by researchers from the Royal Marsden Foundation Trust and the Institute of Cancer Research, and was funded by Sanofi-Aventis. It was published in the peer-reviewed medical journal The Lancet .
This research was covered well by the Daily Mail and The Daily Telegraph , which highlighted that cabazitaxel has not yet received its European licence.
What kind of research was this?
This phase 3 clinical trial compared two drugs, mitoxantrone and cabazitaxel, for men with prostate cancer that had spread to other parts of the body (metastatic cancer). The study, a randomised controlled trial, specifically looked at a subgroup of men whose cancer had progressed after they had received hormone therapy and standard chemotherapy regimens, and who had then received a drug called docetaxel. Docetaxel is currently recommended by the National Institute for Health and Clinical Excellence (NICE) for metastatic prostate cancer that has not responded to hormone treatment (castration-resistant or hormone-refractory prostate cancer) in men who have a Karnofsky performance score of at least 60% (a measure of their ability to perform ordinary tasks). The researchers say that if prostate cancer progresses when a patient is taking docetaxel, mitoxantrone is often administered because it can ease symptoms. However, this or any other drug has not been shown to improve survival in this subgroup of patients. The researchers wanted to assess whether cabazitaxel could improve survival in this group of patients.
What did the research involve?
This study recruited men from 26 countries who had disease progression during or after completion of treatment with docetaxel. The patients had been castrated to remove male hormones that could affect the cancer, either surgically or chemically by using hormone treatment. The study excluded patients who had already received mitoxantrone, radiotherapy to 40% or more of their bone marrow, or cancer therapy (other than hormone treatment) within four weeks of enrolment. The patients’ cancer had spread to at least one other tissue.
A total of 377 patients were assigned to receive mitoxantrone and 378 patients were assigned to receive cabazitaxel. Both drugs were administered intravenously (into a vein) and the patients were given their treatment on day 1 of a 21-day cycle. The treatment was continued for a maximum of 10 cycles.
Over the course of the treatment, the researchers looked at how the tumour responded and took blood tests to measure the level of prostate-specific antigen (PSA), a protein that indicates how the disease is progressing. The researchers measured the time to progression as well as overall survival of the patients. They also measured the amount of pain the patients experienced and monitored any side effects.
What were the basic results?
Patients in the cabazitaxel group had an average of six treatment cycles and the patients in the mitoxantrone group had an average of four cycles. The main reason for the patients stopping treatment was disease progression.
During the study, 12% of patients in the cabazitaxel group and 4% of patients in the mitoxantrone treatment group had the dose of their treatment reduced.
Patients receiving cabazitaxel had a longer time before their disease progressed than the mitoxantrone group (cabazitaxel 2.8 months, 95% confidence interval [CI] 2.4 to 3.0; mitoxantrone 1.4 months, 95% CI 1.4 to 1.7; p<0.0001). In the cabazitaxel group, 14.4% of patients had a reduction in the size of the tumour in response to treatment, compared with 4.4% of patients taking mitoxantrone (p=0.0005). Both groups of patients experienced a similar easing of pain.
Both groups were followed up for an average of 12.8 months. The average overall survival was 15.1 months for the cabazitaxel group, which was longer than the 12.7 months in the mitoxantrone group (p<0.0001).
The most common severe side effect of cabazitaxel was a drop in white blood cell count (neutropenia, which makes the person more prone to infection). Of the patients treated with cabazitaxel, 47% experienced diarrhoea and 6% had severe diarrhoea (less than 1% had severe diarrhoea in the mitoxantrone group).
How did the researchers interpret the results?
The researchers say that, “cabazitaxel is the first drug to improve survival in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel based treatment”. They say that further studies are now planned to evaluate the effect of cabazitaxel on the quality of life in men with castration-resistant prostate cancer.
This phase 3 clinical trial has demonstrated that cabazitaxel extends progression-free survival by an average of 1.4 months and overall survival by an average of 2.3 months in a subgroup of men with advanced castration-resistant prostate cancer which has progressed after treatment with docetaxel. Cabazitaxel has been approved for use in this group of patients by the American Food and Drug Administration this year and is currently being considered by the European Medicines Agency and other UK regulatory bodies.