Chemo Triumphs in Second-Line Metastatic Prostate Cancer
Chemo Triumphs in Second-Line Metastatic Prostate Cancer: 'Practice-changing' results show that cabazitaxel is superior to androgen-signaling inhibitors in second-line treatment of metastatic castrate-resistant prostate cancer.
Chemotherapy with cabazitaxel (Jevtana, Sanofi-Aventis)
beat treatment with an androgen-signaling inhibitor in the second-line
treatment of metastatic castrate-resistant prostate cancer (mCRPC).
The first-line treatment for these patients was with docetaxel and then with one of the androgen-signaling inhibitors, either abiraterone (multiple brands) or enzalutamide (Xtandi, Astellas).
However, there was evidence of rapid disease progression, and so second-line treatment with either cabazitaxel or the other androgen-signaling inhibitor was initiated.
The results showed that men who received carbazitaxel had more than double the rate of imaging-based progression-free survival (PFS; median, 8.0 months vs 3.7 months) and significantly improved overall survival (OS; median, 13.6 months vs 11 months).
"Cabazitaxel remained superior regardless of the androgen-signaling-targeted inhibitor received," note the investigators, led by Ronald de Wit, MD, PhD, Erasmus Medical Center, Rotterdam, the Netherlands.
These findings come from the European CARD trial, which was published on December 26 in the New England Journal of Medicine.
"The CARD trial shows convincingly that cabazitaxel is the preferred therapeutic option over second-line androgen-signaling inhibitors in patients with metastatic castration-resistant prostate cancer who had rapid disease progression while they were receiving first-line androgen-signaling inhibitors," say experts in an accompanying editorial.
"Hence, these results are practice-changing," comment Mario Eisenberger, MD, and Emmanuel Antonarakis, MD, both from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
For example, patients who have a more durable response to first-line abiraterone or enzalutamide, lasting at least 18 months — especially before they receive chemotherapy — might wish to rely on their physician's preference for treatment, in conjunction with appropriate biomarker assessment.
On the other hand, until recently, the choice of either abiraterone followed by enzalutamide or enzalutamide followed by abiraterone has often been preferred over taxane-based chemotherapy after first-line treatment failure because of the ease of administration of these agents and a perception that androgen-signaling inhibitors are roughly as effective as the taxanes.
This may no longer be the case, because preliminary data suggest that the efficacy of sequential androgen-signaling-inhibitor treatment for patients who are no longer deriving benefit from their initial agent is modest and short-lived — "suggesting clinically significant cross-resistance between different androgen-signaling inhibitors," Eisenberger and Antonarakis note.
Given the results of the CARD trial, "it would seem that men treated with androgen-signaling inhibitors before the development of castration-resistant prostate cancer are not likely to benefit from this class of drugs if used subsequently," they state.
The first-line treatment for these patients was with docetaxel and then with one of the androgen-signaling inhibitors, either abiraterone (multiple brands) or enzalutamide (Xtandi, Astellas).
However, there was evidence of rapid disease progression, and so second-line treatment with either cabazitaxel or the other androgen-signaling inhibitor was initiated.
The results showed that men who received carbazitaxel had more than double the rate of imaging-based progression-free survival (PFS; median, 8.0 months vs 3.7 months) and significantly improved overall survival (OS; median, 13.6 months vs 11 months).
"Cabazitaxel remained superior regardless of the androgen-signaling-targeted inhibitor received," note the investigators, led by Ronald de Wit, MD, PhD, Erasmus Medical Center, Rotterdam, the Netherlands.
These findings come from the European CARD trial, which was published on December 26 in the New England Journal of Medicine.
"The CARD trial shows convincingly that cabazitaxel is the preferred therapeutic option over second-line androgen-signaling inhibitors in patients with metastatic castration-resistant prostate cancer who had rapid disease progression while they were receiving first-line androgen-signaling inhibitors," say experts in an accompanying editorial.
"Hence, these results are practice-changing," comment Mario Eisenberger, MD, and Emmanuel Antonarakis, MD, both from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
Other Options to Consider
However, the editorialists stopped short of recommending that all men with mCRPC who are treated with first-line abiraterone or enzalutamide preferentially receive cabazitaxel, because they felt that certain patients who have a more favorable prognosis might wish to choose an alternative approach.For example, patients who have a more durable response to first-line abiraterone or enzalutamide, lasting at least 18 months — especially before they receive chemotherapy — might wish to rely on their physician's preference for treatment, in conjunction with appropriate biomarker assessment.
On the other hand, until recently, the choice of either abiraterone followed by enzalutamide or enzalutamide followed by abiraterone has often been preferred over taxane-based chemotherapy after first-line treatment failure because of the ease of administration of these agents and a perception that androgen-signaling inhibitors are roughly as effective as the taxanes.
This may no longer be the case, because preliminary data suggest that the efficacy of sequential androgen-signaling-inhibitor treatment for patients who are no longer deriving benefit from their initial agent is modest and short-lived — "suggesting clinically significant cross-resistance between different androgen-signaling inhibitors," Eisenberger and Antonarakis note.
Given the results of the CARD trial, "it would seem that men treated with androgen-signaling inhibitors before the development of castration-resistant prostate cancer are not likely to benefit from this class of drugs if used subsequently," they state.
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