Subsequent PFS benefit of apalutamide 'an indicator of effective early intensive treatment' in prostate cancer - Healio

Neeraj Agarwal

The addition of apalutamide to androgen deprivation therapy provided a subsequent PFS benefit for men with nonmetastatic castration-resistant prostate cancer, according to results of a post-hoc analysis of the randomized phase 3 TITAN study presented at Genitourinary Cancers Symposium.

The benefit was observed regardless of the type of first life-extending therapy men received after study treatment, according to the researchers.

“Early intensive treatment is important. We cannot treat most of our patients with standard ADT anymore,” Neeraj Agarwal, MD, prostate cancer physician at Huntsman Cancer Institute and professor of medicine at University of Utah, told Healio. “We have to consider intensification of therapy in our patients with nonmetastatic castration-resistant prostate cancer by adding apalutamide to ADT because there is now strong level-one evidence showing continued improvements in PFS and OS with subsequent therapy. The subsequent PFS benefit observed in our study is an indicator of effective early intensive treatment, is consistent with the benefit we have observed in the TITAN study and, together with the OS benefit, shows the totality of the treatment trajectory.”

Apalutamide (Erleada, Janssen) is a selective next-generation androgen receptor inhibitor for treatment of men with nonmetastatic castration-resistant prostate cancer.

Results of the TITAN study, previously reported by Healio, showed the addition of apalutamide to ADT significantly improved radiographic PFS and OS compared with placebo among men with metastatic castration-sensitive prostate cancer.

For the current post-hoc analysis, Agarwal and colleagues examined whether type of first-line subsequent therapy, hormonal vs. taxane, had a beneficial effect on PFS2 — defined as time from randomization to disease progression on first subsequent therapy for prostate cancer or death, whichever occurred first.

Of the 277 men enrolled on the trial who went on to receive systemic therapy for prostate cancer, 87 had been assigned apalutamide and 190 had been assigned placebo. Eighty-six received subsequent hormonal therapy with either abiraterone acetate (Zytiga, Janssen) plus prednisone or enzalutamide (Xtandi; Astellas, Pfizer) and 99 received taxane therapy with docetaxel or cabazitaxel (Jevtana, Sanofi).

Median duration of treatment in the hormonal therapy group was 11.9 months with apalutamide and 11.1 months with placebo, whereas median treatment duration in the taxane therapy group was 11 months with apalutamide and 11.3 months with placebo.

Results showed significant improvement in PFS2 with apalutamide regardless of subsequent therapy type (HR = 0.66; 95% CI, 0.5-0.87).

Researchers observed a significant reduction in risk for second disease progression among men in the apalutamide group who received hormonal therapy (HR = 0.68; 95% CI, 0.48-0.97) and taxane therapy (HR = 0.67; 95% CI, 0.48-0.94).

Researchers did not perform safety analyses, noting that all men had stopped therapy, mostly because of disease progression.

“These patients were early progressors and so the biggest question is why these patients did not respond and what was different in their tumor biology,” Agarwal told Healio. “Answering this question is important because our next steps will be to build upon the backbone of ADT with apalutamide. We need to identify the molecular targets for these early progressors and figure out these molecular pathways so that we can develop novel agents to target these pathways.” – by Jennifer Southall

Reference:

Agarwal N, et al. Abstract 82. Presented at: Genitourinary Cancers Symposium; Feb. 13-15, 2020; San Francisco.

Disclosures: The study was funded by Janssen Research & Development. Agarwal reports consultant/advisory roles with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Exelixis, Foundation Medicine, Foundation One Inc., Medivation/Astellas, Nektar, Pfizer and Pharmacyclics; and research funding to his institution from Active Biotech, Amgen, AstraZeneca, Bavarian Nordic, Bayer, BN ImmunoTherapeutics, Bristol-Myers Squibb, Calithera Biosciences, Celldex, Eisai, Exelixis, Genentech, GlaxoSmithKline, Immunomedics, Janssen, Merck, Newlink Genetics, Novartis, Pfizer, Prometheus, Rexahn Pharmaceuticals, Sanofi, Takeda and TRACON Pharma. Please see the abstract for all other authors’ relevant financial disclosures.

Neeraj Agarwal

The addition of apalutamide to androgen deprivation therapy provided a subsequent PFS benefit for men with nonmetastatic castration-resistant prostate cancer, according to results of a post-hoc analysis of the randomized phase 3 TITAN study presented at Genitourinary Cancers Symposium.

The benefit was observed regardless of the type of first life-extending therapy men received after study treatment, according to the researchers.

“Early intensive treatment is important. We cannot treat most of our patients with standard ADT anymore,” Neeraj Agarwal, MD, prostate cancer physician at Huntsman Cancer Institute and professor of medicine at University of Utah, told Healio. “We have to consider intensification of therapy in our patients with nonmetastatic castration-resistant prostate cancer by adding apalutamide to ADT because there is now strong level-one evidence showing continued improvements in PFS and OS with subsequent therapy. The subsequent PFS benefit observed in our study is an indicator of effective early intensive treatment, is consistent with the benefit we have observed in the TITAN study and, together with the OS benefit, shows the totality of the treatment trajectory.”

Apalutamide (Erleada, Janssen) is a selective next-generation androgen receptor inhibitor for treatment of men with nonmetastatic castration-resistant prostate cancer.

Results of the TITAN study, previously reported by Healio, showed the addition of apalutamide to ADT significantly improved radiographic PFS and OS compared with placebo among men with metastatic castration-sensitive prostate cancer.

For the current post-hoc analysis, Agarwal and colleagues examined whether type of first-line subsequent therapy, hormonal vs. taxane, had a beneficial effect on PFS2 — defined as time from randomization to disease progression on first subsequent therapy for prostate cancer or death, whichever occurred first.

Of the 277 men enrolled on the trial who went on to receive systemic therapy for prostate cancer, 87 had been assigned apalutamide and 190 had been assigned placebo. Eighty-six received subsequent hormonal therapy with either abiraterone acetate (Zytiga, Janssen) plus prednisone or enzalutamide (Xtandi; Astellas, Pfizer) and 99 received taxane therapy with docetaxel or cabazitaxel (Jevtana, Sanofi).

Median duration of treatment in the hormonal therapy group was 11.9 months with apalutamide and 11.1 months with placebo, whereas median treatment duration in the taxane therapy group was 11 months with apalutamide and 11.3 months with placebo.

Results showed significant improvement in PFS2 with apalutamide regardless of subsequent therapy type (HR = 0.66; 95% CI, 0.5-0.87).

Researchers observed a significant reduction in risk for second disease progression among men in the apalutamide group who received hormonal therapy (HR = 0.68; 95% CI, 0.48-0.97) and taxane therapy (HR = 0.67; 95% CI, 0.48-0.94).

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Researchers did not perform safety analyses, noting that all men had stopped therapy, mostly because of disease progression.

“These patients were early progressors and so the biggest question is why these patients did not respond and what was different in their tumor biology,” Agarwal told Healio. “Answering this question is important because our next steps will be to build upon the backbone of ADT with apalutamide. We need to identify the molecular targets for these early progressors and figure out these molecular pathways so that we can develop novel agents to target these pathways.” – by Jennifer Southall

Reference:

Agarwal N, et al. Abstract 82. Presented at: Genitourinary Cancers Symposium; Feb. 13-15, 2020; San Francisco.

Disclosures: The study was funded by Janssen Research & Development. Agarwal reports consultant/advisory roles with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Exelixis, Foundation Medicine, Foundation One Inc., Medivation/Astellas, Nektar, Pfizer and Pharmacyclics; and research funding to his institution from Active Biotech, Amgen, AstraZeneca, Bavarian Nordic, Bayer, BN ImmunoTherapeutics, Bristol-Myers Squibb, Calithera Biosciences, Celldex, Eisai, Exelixis, Genentech, GlaxoSmithKline, Immunomedics, Janssen, Merck, Newlink Genetics, Novartis, Pfizer, Prometheus, Rexahn Pharmaceuticals, Sanofi, Takeda and TRACON Pharma. Please see the abstract for all other authors’ relevant financial disclosures.