US FDA approves cabazitaxel for late-stage prostate cancer


Somewhat “out of the blue,” the US Food and Drug Administration (FDA), earlier today, approved Sanofi-Aventis’s “second-generation” taxane, cabazitaxel (Jevtana®) in combination with prednisone for the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) who have already progressed after treatment with docetaxel.

The “New” Prostate Cancer InfoLink had been expecting this approval, and had hoped that it would occur this year, but this is a much faster approval than probably anyone was expecting. There may be a lesson here for the bio/pharmaceutical industry that if you identify a clearly unmet need, conduct well-organized clinical trials that meet clearly defined endpoints, and ensure that your submission is well managed and coordinated, that the FDA, under it’s new leadership, will act promptly to approve needed therapeutic drugs. The regulatory submission for cabazitaxel was finalized only in March this year, and the drug has been approved just 3 months later.

This is the first time ever that we can remember two important new treatments being approved for the treatment of prostate cancer in a single year. Cabazitaxel, like docetaxel, is an injectable drug that will have to be administered by intravenous infusion. It is only the third drug that has clearly shown any overall survival benefit in the treatment of men with mCRPC.

According to the media release from Sanofi-Aventis, the Phase III TROPIC trial showed that cabazitaxel + prednisone reduced the risk of death by 30 percent (a hazard ratio of 0.70) compared to mitoxantrone + prednisone. Earlier reports have indicated that cabazitaxel + prednisone extended median overall survival by approximately 2.5 months compared to mitoxantrone + prednisone in this very advanced group of patients.

It is important to understand that cabazitaxel is a drug with a list of significant side effects, although many of these should be manageable with supportive care products that are used regularly by oncologists. According to the company’s media release,

… the most common (≥ 10%) adverse reactions (grade 1-4) [observed in the TROPIC trial] were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysguesia, cough, arthralgia, and alopecia.

The most common (≥ 5%) grade 3-4 adverse reactions in patients who received [cabazitaxel] were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia. The most common adverse reactions leading to treatment discontinuation in the [cabazitaxel] group were neutropenia and renal failure.

However, there is no mention in the company media release — nor in any statement from the US FDA — that clinical use of cabazitaxel will be restricted by a REMS (as discussed in a prior commentary on this web site).

It will be important to watch exactly how cabazitaxel gets used in clinical practice over the next couple of years. A key question is going to be whether patients who are chemotherapy-naïve and are treated with cabazitaxel  before they receive docetaxel demonstrate an overall survival equivalent to the sum of the overall survivals demonstrated by docetaxel followed by cabazitaxel (i.e., about 5 months in total). Another important question will be whether docetaxel can offer an extension of survival if administered after cabazitaxel.

As if these questions weren’t enough, there is also the critical question of when to administer chemotherapy to men who have previously been treated with sipuleucel-T. The effects of steroids like prednisone — which are immune system suppressants — on men who have received immunotherapy with drugs like sipuleucel-T is utterly unknown at this time, and will need to be teased out with great care.

2 Responses

  1. My husband will have his third treatment of cabazitaxel in 3 days; he gets them every 21 days. He has had no side effects from that drug. He has had some side effects of weakness, sick at his stomach, and bones hurting from the shot they give the day after to make the bone marrow produce more white cells. His second treatment they did not give him the shot and he had no side effects. His WBC is 1.6 and his RBC is low too, so he will probably have to have a shot this next treatment. He thinks the shot is worth the way he felt after the first 4 days after it. He has felt better than he has in a long time.

    He has gone through all the other treatments over the last 7 years but at this time these meds have increased his quality of life. Our doctor has not given us any kind of time frame so we are not sure of what it means when it says this could add months to his life. How do they know. Right now I am just happy he is here with me and pray he will be as long as possible.

  2. Dear Barbara:

    Obviously I am glad to hear that your husband seems to be responding to cabazitaxel treatment — and that he seems to be doing so without any significant side effects from the cabazitaxel itself.

    It is extremely difficult to tell for exactly how long any particular patient may continue to respond to a new drug like cabazitaxel. Some men don’t respond at all; others seem to respond for extended periods of time. However, in the clinical trial of cabazitaxel that led to its approval, the survival of patients after they started on the drug ranged from about 14 months to a little more than 16 months (see Table 3 of the full prescribing information for cabazitaxel), and at that point in the trial 38% of the men who had been treated with Jevtana were still alive. Hopefully you will see him do well for at least that sort of period of time, and maybe a good deal longer.

    Mike

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