Apalutamide in nmCRPC: QOL as Good as ADT Alone

Pam Harrison

March 27, 2018

COPENHAGEN — New results suggest that health-related quality of life (HRQOL) is good with the new-generation antiandrogen inhibitor apalutamide (Erleada, Janssen), which recently became the first agent to be approved for use in men with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

"It was extremely important to look at quality of life among patients in this category of disease because, by definition, they are asymptomatic, so you take someone who is feeling perfectly well and you give them an active agent, and we could have seen a worsening in quality of life," lead author Fred Saad, MD, professor of surgery, University of Montreal, Quebec, Canada, told Medscape Medical News.

"So we were really pleased to see that we didn't detect any difference in quality of life between the two groups, and if anything, the placebo arm seemed to have a slightly lower quality of life than men getting apalutamide, which is very reassuring in an asymptomatic population," he added.

The team found that HRQOL is not only maintained when apalutamide is added to androgen deprivation therapy (ADT), but it may be slightly better than it is for men treated with ADT alone, according to an updated report from the pivotal Selective Prostate Androgen Receptor Targeting With ARN-509 (SPARTAN) study.

The study was presented during a poster session at the European Association of Urology (EAU) 2018 Congress.


When apalutamide was approved in the United States in February 2018, it became the first drug for nmCRPC. The approval also marked the first time that the US Food and Drug Administration (FDA) used metastasis-free survival (MFS) as the primary endpoint in its decision making.

The approval was based on results from the phase 3 SPARTAN trial, which included 1207 patients (median age, 74 years) with nmCRPC whose prostatic-specific antigen (PSA) doubling time was 10 months or less.

Multiple studies indicate that a rapid PSA doubling time predicts rapid occurrence of metastasis and death, so these patients were destined to develop metastatic disease in a relatively short amount of time, Saad pointed out.

The patients were already undergoing ADT with either a gonadotropin-releasing hormone analogue or surgical castration.

They were randomly assigned in a 2-to-1 ratio to receive either apalutamide (240 mg/day) or placebo.

The median time to apalutamide exposure was 16.9 months, vs 11.2 months for placebo.

HRQOL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the EuroQoL Group's EQ-5D-3L, which are patient-reported questionnaires.

Patients completed each questionnaire at baseline and on day 1 of cycles two to seven, cycle 9, cycle 11, and cycle 13, then every 4 months for the duration of treatment, and at 1 year after treatment had been discontinued.

"Analyses were conducted on FACT-P total score and all subscales, including FACT-G, a more general evaluation of HRQOL," the investigators observe.

Of a total score of 108 on the FACT-G questionnaire, the mean baseline score for men receiving additional apalutamide was 83, compared with 84 for the control patients, who received placebo.

These scores are consonant with the FACT-G scores for adult patients who do not have prostate cancer, for whom the mean score is 81, the researchers point out.

In a comparison of HRQOL among men in the apalutamide arm to the control patients over time, mean changes from baseline in the FACT-P total and subscale scores were generally not significantly different — if anything, any significant differences in FACT-P total and subscale scores were in favor of the patients who received additional apalutamide, the investigators observe.

Most importantly, both FACT-G scores and other patient-reported scores were maintained with the dual treatment strategy starting from the initiation of treatment at both time points of HRQOL assessment, they add.

Table. HRQOL Scores at Baseline and at Cycles 2 and 3

  Baseline Cycle 2* Cycle 3
Placebo 83.40 83.48 83.68
Apalutamide 84.10 84.28 83.29
*8 weeks from baseline
12 weeks from baseline


Waiting Too Long

Saad explained that, for patients who are at high risk for metastases, treatment with drugs such as apalutamide should not be delayed.

The SPARTAN trial was published in the New England Journal of Medicine in February. The results showed that the addition of apalutamide to ADT decreased the risk for metastases and death by 72% and prolonged median metastasis-free survival by more than 2 years in men with high-risk prostate cancer (P < .001).

Investigators compared patients in the placebo arm of the study who, upon developing metastatic disease, received apalutamide with patients who received apalutamide up front on study enrollment.

"Even after subsequent therapy, the arms of the study continue to separate," Saad noted.

"So that means that even though we started treatment early, as soon as patients became metastatic, we never caught up to patients who started apalutamide immediately," he said.

"That, in my mind, helps convince me that we are probably going to see an overall survival advantage with additional apalutamide, because even if you treat patients very early on in the metastatic phase, you never catch up to where you'd be when starting treatment prior to them developing metastases," he said.

"So hopefully we are delaying disease without affecting the patient's quality of life, especially because this is a group of patients whose quality of life is very comparable to men who don't even have prostate cancer," Saad concluded.

Iatrogenic-Induced Disease

Asked by Medscape Medical News to comment on the study, Marc Garnick, MD, Gorman Brothers Professor of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, noted that nmCRPC is a novel, iatrogenic-induced disease.

"While the use of apalutamide has improved the time to the development of metastatic disease, many questions remain," Garnick said.

For example, the current findings do not clarify how long patients received ADT before the development of this ADT-induced nmCRPC.

Moreover, the fact that HRQOL was similar for men who received an agent and for those who received placebo is counterintuitive and suggests that the instruments used to assess HRQOL may need to be better validated when assessing apalutamide, Garnick observed.

Garnick also noted that "it would be important to analyze concomitant medications and comorbidities before any endorsement of the presented findings can be accepted or properly interpreted."

The study was supported by Janssen Research and Development. Dr Saad has served as a consultant to and receives institutional research funding from Astellas and Janssen. Dr Garnick is editor-in-chief of Harvard Medical School's Annual Report on Prostate Diseases and its website.

European Association of Urology (EAU) 2018 Congress. Abstract 763, presented March 19, 2018.


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