ASCO 2020: LACOG 0415: Phase II Randomized Study of Abiraterone Acetate plus Prednisone Added to ADT Versus Apalutamide Alone vs AAP+APA in Patients with Advanced Prostate Cancer

(UroToday.com) The standard of care for patients with advanced prostate cancer includes a backbone of androgen deprivation therapy (ADT), in combination with androgen receptor antagonists such as enzalutamide, apalutamide, or abiraterone. However, it is unknown if androgen suppression without the backbone of a GnRH agent such as leuprolide or degarelix is effective or safe. This study evaluates this hypothesis by randomizing patients to one of three arms which include ADT + Abiraterone + Prednisone (ADT+AAP), apalutamide alone (APA), or abiraterone + prednisone + apalutamide (APA + AAP).


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The study design is shown above. 128 patients were randomized to one of the three arms mentioned above and the primary endpoint was PSA≤0.2 ng/mL at week 25. Patients had either N+ disease not amenable for local therapy, biochemical relapse, or metastatic disease and non-castrate testosterone levels at baseline.

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Baseline characteristics are shown above. This was a heterogeneous patient population - the majority of patients had metastatic hormone-sensitive disease (74%), 9% had node-positive disease, and 17% had a biochemical relapse. About 40% of patients had previously had a prostatectomy and 40% had radiation in each arm.


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At week 25, 76% of pts in AAP+ADT arm, 59% in APA, and 80% in APA+AAP had achieved the primary endpoint. One patient in every arm had clinical progression of disease.

Testosterone levels differed significantly between the apalutamide alone arm and the other two arms. Those with APA alone had an increase by a mean of 134 ng/dL, compared to patients on ADT + AAP or APA + AAP.


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In terms of treatment-related adverse events, 71% of patients in the AAP+ADT arm experienced an event, compared with 64% in the APA arm and 65% in the APA+AAP arm. Patients in the APA+AAP arm had the highest rate of Grade 3 or higher event (16%), followed by 12% in the AAP+ADT arm and 9% in the APA arm. 6 patients discontinued the APA+AAP arm due to toxicity, 2 in the APA arm, and 1 from the AAP+ADT arm. Of note, 55% of men in the APA arm reported gynecomastia compared to 20% in the APA + AAP arm and ADT+AAP arm.

Also of note, only 5% of patients in the APA alone arm experienced hot flushes, compared with 38% of patients on ADT+AAP and 30% of patients on APA+AAP.

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Despite the rise in testosterone, the mean FACT-P quality of life score did not seem significantly better for APA alone compared with ADT + AAP.

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Based on the primary endpoint, combination therapy (AAP+ADT or AAP+APA) was more effective than single-agent therapy (APA) at achieving PSA ≤ 0.2 ng/mL.  Serum testosterone increased with APA alone than the other two arms, but this was not associated with an improvement in overall survival.  The safety profiles differed between three arms with more gynecomastia in the APA alone and hot flushes in the other two arms. While not reported in this abstract, would be interesting to know in future studies if there were significant differences in major adverse cardiovascular events between the three arms. Also, for patients who have a significant decline in quality of life with ADT and do not tolerate leuprolide, this data set provides compelling evidence that they may tolerate apalutamide alone better without a significant compromise in efficacy.

Presented by: Fernando Maluf, MD, Associate Director – Oncology Center - Beneficência Portuguesa, São Paulo Member of Steering Committee – Oncology Center – Albert Einstein Hospital, São Paulo

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020

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