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.
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,
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.