Cabazitaxel improves outcomes among certain men with metastatic prostate cancer - Healio

Ronald de Wit

BARCELONA, Spain — Cabazitaxel significantly improved outcomes compared with androgen receptor-targeted therapies for certain men with previously treated metastatic castration-resistant prostate cancer, according to results of the randomized CARD study presented at European Society for Medical Oncology Congress.

Cabazitaxel (Jevtana, Sanofi Genzyme) — a semi-synthetic derivative of a natural taxoid — more than doubled radiographic PFS and reduced risk for death by 36% compared with abiraterone acetate (Zytiga, Janssen) and enzalutamide (Xtandi; Astellas, Pfizer).

“This can be considered practice changing,” Ronald de Wit, MD, PhD, full professor at Erasmus Medical Center Cancer Center in the Netherlands, said during his presentation. “These results are both statistically significant and clinically important, and they support the use of cabazitaxel over abiraterone or enzalutamide in this setting.”

Taxanes — including docetaxel and cabazitaxel — and androgen-signaling targeted inhibitors (ARTA), such as abiraterone acetate and enzalutamide, are standard treatments for metastatic castration-resistant prostate cancer.

However, the ideal sequence of these treatments has not been established. Patients who progress on enzalutamide may not respond to subsequent abiraterone and vice versa, according to study background. Cabazitaxel, however, continues to demonstrate activity among men who progress on prior docetaxel, enzalutamide or abiraterone.

The multicenter, open-label CARD study compared the efficacy and safety of cabazitaxel vs. abiraterone or enzalutamide for men with castration-resistant prostate cancer who progressed after 12 months of treatment or less on the alternative ARTA and also received prior docetaxel.

The study included 255 men (median age, 70 years; 31% age 75 or older).

Researchers randomly assigned 129 of the men to cabazitaxel dosed at 25 mg/m² via IV every 3 weeks plus prednisone and granulocyte-colony stimulating factor. The other 126 men received abiraterone dosed at 1,000 mg daily plus prednisone, or enzalutamide dosed at 160 mg daily.

Investigators stratified randomization by ECOG performance status (0 or 1 vs. 2), time to progression on prior ARTA (0 to 6 months vs. > 6 to 12 months) and ARTA timing (prior to or after docetaxel).

Patient characteristics were well-balanced between groups, including with regard to prior ARTA exposure — abiraterone or enzalutamide — and the sequence of prior ARTA and docetaxel, de Wit said.

Radiographic PFS served as the primary endpoint. Key secondary endpoints included OS, PFS, PSA response and tumor response. Additional secondary endpoints included pain response, time to symptomatic skeletal events, safety, health care-related quality of life and biomarkers.

Median follow-up was 9.2 months.

Men assigned cabazitaxel underwent a higher median number of treatment cycles (7 vs. 4). Median treatment duration was 22 weeks (range, 3-88) in the cabazitaxel group and 12.5 weeks (range, 2-141) in the abiraterone/enzalutamide group.

The study met its primary endpoint, as results showed significantly longer median radiographic PFS in the cabazitaxel group (8 months vs. 3.7 months; HR = 0.54; 95% CI, 0.4-0.73).

A preplanned subgroup analysis showed consistent benefit with cabazitaxel, de Wit said.

Analysis of secondary efficacy outcomes showed a benefit with cabazitaxel with regard to median OS despite crossover (13.6 months vs. 11 months; HR = 0.64; 95% CI, 0.46-0.89); PFS (median, 4.4 months vs. 2.7 months; HR = 0.52; 95% CI, 0.4-0.68); percentage of men with confirmed PSA50 response, defined as greater than 50% decline in PSA (35.7% vs. 13.5%; P = .0002); and objective tumor response (36.5% vs. 11.5%; P = .004).

Investigators reported improvements in symptomatic skeletal events (not reached vs. 16.7 months; HR = 0.59; 95% CI, 0.35-1.01) and pain response (45% vs. 19.3%; P < .0001) among men assigned cabazitaxel.

Radiographic PFS with cabazitaxel remained superior regardless of abiraterone/enzalutamide sequence, de Wit said. Cabazitaxel conferred benefit to men who received enzalutamide after docetaxel and abiraterone (median, 7.4 months vs. 4.8 months; HR = 0.57; 95% CI, 0.36-0.9), as well as men who received abiraterone after docetaxel and enzalutamide (median, 8.2 months vs. 3.4 months; HR = 0.44; 95% CI, 0.29-0.67).

Grade 3 or higher adverse events occurred at comparable rates in the cabazitaxel and androgen receptor-targeted therapy groups (56.3% vs. 52.4%). The most notable were renal disorders (3.2% for cabazitaxel vs. 8.1% for androgen receptor-targeted therapy), infections (7.9% vs. 7.3%), musculoskeletal pain or discomfort (1.6% vs. 5.6%), cardiac disorders (0.8% vs. 4.8%), spinal cord or nerve root disorders (2.4% vs. 4%), asthenia/fatigue (4% vs. 2.4%), peripheral neuropathy (3.2% vs. 0%), febrile neutropenia (3.2% vs. 0%) and diarrhea (3.2% vs. 0%).

Twenty-five patients (19.8%) assigned cabazitaxel and 11 (8.9%) assigned abiraterone/enzalutamide discontinued treatment due to adverse events; this primarily was due to longer treatment exposure, de Wit said. A lower percentage of men assigned cabazitaxel than abiraterone/enzalutamide discontinued treatment due to disease progression (43.7% vs. 71%).

Seven men (5.6%) assigned cabazitaxel and 14 men (11.3%) assigned androgen receptor-targeted therapy experienced adverse events that led to death. – by Mark Leiser

Reference: de Wit R, et al. Abstract LBA13_PR. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Sanofi funded this study. de Wit reports advisory roles with Bayer, Clovis Oncology, Janssen, Merck, Roche and Sanofi; honoraria from Merck and Sanofi; and institutional grants from Bayer and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.

Ronald de Wit

BARCELONA, Spain — Cabazitaxel significantly improved outcomes compared with androgen receptor-targeted therapies for certain men with previously treated metastatic castration-resistant prostate cancer, according to results of the randomized CARD study presented at European Society for Medical Oncology Congress.

Cabazitaxel (Jevtana, Sanofi Genzyme) — a semi-synthetic derivative of a natural taxoid — more than doubled radiographic PFS and reduced risk for death by 36% compared with abiraterone acetate (Zytiga, Janssen) and enzalutamide (Xtandi; Astellas, Pfizer).

“This can be considered practice changing,” Ronald de Wit, MD, PhD, full professor at Erasmus Medical Center Cancer Center in the Netherlands, said during his presentation. “These results are both statistically significant and clinically important, and they support the use of cabazitaxel over abiraterone or enzalutamide in this setting.”

Taxanes — including docetaxel and cabazitaxel — and androgen-signaling targeted inhibitors (ARTA), such as abiraterone acetate and enzalutamide, are standard treatments for metastatic castration-resistant prostate cancer.

However, the ideal sequence of these treatments has not been established. Patients who progress on enzalutamide may not respond to subsequent abiraterone and vice versa, according to study background. Cabazitaxel, however, continues to demonstrate activity among men who progress on prior docetaxel, enzalutamide or abiraterone.

The multicenter, open-label CARD study compared the efficacy and safety of cabazitaxel vs. abiraterone or enzalutamide for men with castration-resistant prostate cancer who progressed after 12 months of treatment or less on the alternative ARTA and also received prior docetaxel.

The study included 255 men (median age, 70 years; 31% age 75 or older).

Researchers randomly assigned 129 of the men to cabazitaxel dosed at 25 mg/m² via IV every 3 weeks plus prednisone and granulocyte-colony stimulating factor. The other 126 men received abiraterone dosed at 1,000 mg daily plus prednisone, or enzalutamide dosed at 160 mg daily.

Investigators stratified randomization by ECOG performance status (0 or 1 vs. 2), time to progression on prior ARTA (0 to 6 months vs. > 6 to 12 months) and ARTA timing (prior to or after docetaxel).

Patient characteristics were well-balanced between groups, including with regard to prior ARTA exposure — abiraterone or enzalutamide — and the sequence of prior ARTA and docetaxel, de Wit said.

Radiographic PFS served as the primary endpoint. Key secondary endpoints included OS, PFS, PSA response and tumor response. Additional secondary endpoints included pain response, time to symptomatic skeletal events, safety, health care-related quality of life and biomarkers.

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Median follow-up was 9.2 months.

Men assigned cabazitaxel underwent a higher median number of treatment cycles (7 vs. 4). Median treatment duration was 22 weeks (range, 3-88) in the cabazitaxel group and 12.5 weeks (range, 2-141) in the abiraterone/enzalutamide group.

The study met its primary endpoint, as results showed significantly longer median radiographic PFS in the cabazitaxel group (8 months vs. 3.7 months; HR = 0.54; 95% CI, 0.4-0.73).

A preplanned subgroup analysis showed consistent benefit with cabazitaxel, de Wit said.

Analysis of secondary efficacy outcomes showed a benefit with cabazitaxel with regard to median OS despite crossover (13.6 months vs. 11 months; HR = 0.64; 95% CI, 0.46-0.89); PFS (median, 4.4 months vs. 2.7 months; HR = 0.52; 95% CI, 0.4-0.68); percentage of men with confirmed PSA50 response, defined as greater than 50% decline in PSA (35.7% vs. 13.5%; P = .0002); and objective tumor response (36.5% vs. 11.5%; P = .004).

Investigators reported improvements in symptomatic skeletal events (not reached vs. 16.7 months; HR = 0.59; 95% CI, 0.35-1.01) and pain response (45% vs. 19.3%; P < .0001) among men assigned cabazitaxel.

Radiographic PFS with cabazitaxel remained superior regardless of abiraterone/enzalutamide sequence, de Wit said. Cabazitaxel conferred benefit to men who received enzalutamide after docetaxel and abiraterone (median, 7.4 months vs. 4.8 months; HR = 0.57; 95% CI, 0.36-0.9), as well as men who received abiraterone after docetaxel and enzalutamide (median, 8.2 months vs. 3.4 months; HR = 0.44; 95% CI, 0.29-0.67).

Grade 3 or higher adverse events occurred at comparable rates in the cabazitaxel and androgen receptor-targeted therapy groups (56.3% vs. 52.4%). The most notable were renal disorders (3.2% for cabazitaxel vs. 8.1% for androgen receptor-targeted therapy), infections (7.9% vs. 7.3%), musculoskeletal pain or discomfort (1.6% vs. 5.6%), cardiac disorders (0.8% vs. 4.8%), spinal cord or nerve root disorders (2.4% vs. 4%), asthenia/fatigue (4% vs. 2.4%), peripheral neuropathy (3.2% vs. 0%), febrile neutropenia (3.2% vs. 0%) and diarrhea (3.2% vs. 0%).

Twenty-five patients (19.8%) assigned cabazitaxel and 11 (8.9%) assigned abiraterone/enzalutamide discontinued treatment due to adverse events; this primarily was due to longer treatment exposure, de Wit said. A lower percentage of men assigned cabazitaxel than abiraterone/enzalutamide discontinued treatment due to disease progression (43.7% vs. 71%).

Seven men (5.6%) assigned cabazitaxel and 14 men (11.3%) assigned androgen receptor-targeted therapy experienced adverse events that led to death. – by Mark Leiser

Reference: de Wit R, et al. Abstract LBA13_PR. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

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Disclosures: Sanofi funded this study. de Wit reports advisory roles with Bayer, Clovis Oncology, Janssen, Merck, Roche and Sanofi; honoraria from Merck and Sanofi; and institutional grants from Bayer and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.

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