Apalutamide Maintains Health-Related QoL Among Men With Nonmetastatic CRPC

With more than 4 years of follow-up, the health-related quality of life (HRQoL) of men with nonmetastatic castration-resistant prostate cancer (CRPC) receiving androgen deprivation therapy (ADT) was shown to be maintained with the addition of apalutamide (Erleada), according to results from the final analysis of the phase 3 SPARTAN trial that was presented during the 2020 ESMO Virtual Congress.¹

Moreover, the HRQoL in patients receiving placebo began to decline after about 1 year.

Among patients who remained on treatment and for whom patient-reported outcome data were available, the least squares mean changes from baseline using mixed model for repeated measures (LSM-MMRM) showed that Functional Assessment of Cancer Therapy-Prostate (FACT-P) changes from baseline to cycles 21 and 25 of therapy favored apalutamide compared with placebo (P = .0138; P = .0009, respectively).

Additionally, patients who received apalutamide generally maintained favorable FACT-P subscales and EQ-5D-3L visual analog scale (VAS) scores, whereas the scores tended to decline in patients who received placebo.

The SPARTAN trial randomized 1207 patients with nonmetastatic CRPC receiving ongoing ADT 2:1 to 240 mg of daily apalutamide or placebo.

The primary analysis of the study showed that apalutamide significantly improved metastasis-free survival, delayed the time to metastasis, and extended progression-free survival compared with placebo.² Additionally, apalutamide delayed the time to symptomatic progression versus placebo.

During the 2020 ASCO Virtual Scientific Program, results of the final analysis of the SPARTAN trial were presented, showing significantly improved overall survival (OS) with apalutamide compared with placebo. At 52 months of follow-up, the median OS was 73.9 months with apalutamide versus 59.9 months with placebo (HR, 0.78).³

Apalutamide also delayed the time to initiation of cytotoxic chemotherapy versus placebo.

The median treatment duration at 52 months of follow-up was 32.9 months with apalutamide versus 11.5 months with placebo.

In the HRQoL analysis, investigators used the FACT-P and EQ-5D-3L questionnaires at baseline, and on day 1 of cycle 1. Assessments were also performed every cycle from cycles 2 to 6, every 2 cycles from cycles 7 and 13, every 4 cycles thereafter during treatment, and at the end of treatment. Post-progression assessments were performed every 4 months for up to 1 year.

No adjustments for multiplicity were made.

Baseline patient characteristics were similar between those treated with apalutamide (n = 806) and those treated with placebo (n = 401).

The median age was 74 years, and the median time from initial diagnosis to randomization was nearly 8 years (7.95 with apalutamide vs 7.85 with placebo).

Patients had a median prostate-specific antigen level of over 7.5 ng/mL at study entry. Additionally, 10% of patients on both arms had prior exposure to a bone-sparing agent.

The majority of patients had an ECOG performance status of 0 (77% with apalutamide; 78% with placebo); the remaining patients had a score of 1.

At initial diagnosis in the patients receiving apalutamide (n = 784), 19% had a Gleason score of less than 7, 37% had a score of 7, and 43% had scores greater than 7. These findings were nearly identical among the placebo group (n = 387; 19%, 38%, and 44%, respectively).

Previous prostate cancer treatments included surgery, radiotherapy, gonadotropin-releasing hormone analog agonist, first-generation antiandrogen agents such as flutamide (Eulexin), bicalutamide (Casodex), and nilutamide (Nilandron), orchiectomy, other hormonal therapy, adjuvant or neoadjuvant chemotherapy, and other prostate cancer therapy.

In the apalutamide-treated group, the mean total FACT-P score at baseline was 117.2 (standard deviation [SD], 19.2), and the mean FACT-General (FACT-G) score was 84.1 (SD, 14.4). The mean FACT-P score among patients in the placebo group was 116.6 (SD, 19.3), and the mean FACT-G score was 83.4 (SD, 14.2).

The mean subscale scores in the apalutamide group were 24.8 (SD, 3.4) for physical wellbeing, 20.9 (SD, 5.8) for social and family wellbeing, 18.4 (SD, 4.1) for emotional wellbeing, 20.3 (SD, 5.9) for functional wellbeing, 33.3 (SD, 6.5) for prostate cancer, and 12.4 (SD, 3.7) for pain-related score. These measures were similar among the placebo group.

Regarding baseline EQ-5D-3L scores, 97% of patients treated with apalutamide had a mean health utility index score of 0.85 (SD, 0.17). Ninety-eight percent of patients had a mean health status VAS score of 76.2 (SD, 17.3). In the placebo arm, 98% of patients had similar baseline scores.

The HRQoL analysis summarized the median times to degradation in FACT-P total score and subscales. In the apalutamide group, FACT-P scores were 6.6 months (95% CI, 5.6-8.3) overall, 6.6 months (95% CI, 5.6-8.4) for physical wellbeing, 7.5 months (95% CI, 5.6-11.1) for social/family wellbeing, 14.7 months (95% CI, 11.1-18.6) for emotional wellbeing, 4.6 months (95% CI, 3.8-5.6) for functional wellbeing, 3.8 months (95% CI, 3.7-4.7) for prostate cancer subscale, 7.4 months (95% CI, 6.5-9.3) for trial outcome index, 6.4 months (95% CI, 5.5-7.3) for pain-related subscale, 7.5 months (95% CI, 6.5-10.2) for advanced prostate symptom index, and 9.3 months (95% CI, 7.4-14.7) for FACT-G score.

In the placebo arm these measures were 8.4 months (95% CI, 6.5-12.9), 7.4 months (95% CI, 5.6-11.1), 4.9 months (95% CI, 3.8-8.4), 14.8 months (95% CI, 10.6-19.3), 6.5 months (95% CI, 4.7-9.3), 3.8 months (95% CI, 2.9-4.8), 11.1 months (95% CI, 8.3-14.8), 4.6 months (95% CI, 3.7-5.7), 6.5 months (95% CI, 4.7-9.3), and 13.0 months (95% CI, 8.4-18.5), respectively.

Additionally, most patients who answered question GP5 of the FACT-P indicated that they were “not at all bothered by [the] side effects of treatment.” This bother did not increase in the apalutamide or placebo groups over time.

Responses to question GP1 regarding lack of energy indicated that levels of fatigue remained mostly consistent with baseline levels among both groups. Moreover, fatigue levels were similar between groups and remained similar over time.

The data from the SPARTAN trial, regarding both efficacy and HRQoL, support the use of adding apalutamide to ADT as a treatment option for men with nonmetastatic CRPC, the investigators concluded.

References

1. Oudard S, Hadaschik B, Saad F, et al. Health-related quality of life (HRQoL) at final analysis of the SPARTAN study of apalutamide (APA) vs placebo (PBO) in patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen deprivation therapy (ADT). Presented at: 2020 ESMO Congress; September 19-21, 2020; Virtual. Abstract 632P.
2. Small EJ, Saad F, Chowdhury S et al. SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2018;36(suppl 6S):161.doi:10.1200/JCO.2018.36.6_suppl.161
3. Small EJ, Saad F, Chowdhury S, et al. Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2020;38(suppl 15):5516. doi:10.1200/JCO.2020.38.15_suppl.5516