Table 4 PRO claims granted by the FDA and the EMA

Xtandi/enzalutamide

“Baseline data: 28% had a mean Brief Pain Inventory score of ≥ 4”

“28.4% had a mean Brief Pain Inventory score of ≥ 4 (mean of patient’s reported worst pain over the previous 24 hours calculated for seven days prior to randomization).”

“P-value is derived from a log-rank test stratified by baseline ECOG performance status score (0–1 vs. 2) and mean baseline pain score (BPI-SF score < 4 vs. ≥ 4)”

Overall survival presented in a table by subgroup; one of the subgroups was “Baseline mean pain score on BPI-SF Question #3^a” of < 4 compared to ≥ 4

Zytiga/abiraterone

Study 1 (baseline data):

Study 302:

“45% had a Brief Pain Inventory-Short Form score of ≥ 4 (patient’s reported worst pain over the previous 24 hours)”

“A score of 0–1 on Brief Pain Inventory-Short Form (BPI-SF) worst pain in last 24 hours was considered symptomatic, and a score of 2–3 was considered mildly symptomatic.”

Study 2:

“Baseline pain assessment was 0–1 (asymptomatic) in 66% of patients and 2–3 (mildly symptomatic) in 26% of patients as defined by the Brief Pain Inventory-Short Form (worst pain over the last 24 hours).”

“Pain: Treatment with ZYTIGA significantly reduced the risk of average pain intensity progression by 18% compared with placebo (p = 0.0490). The median time to progression was 26.7 months in the ZYTIGA group and 18.4 months in the placebo group.”

“The median time to opiate use for prostate cancer pain was not reached for patients receiving ZYTIGA and was 23.7 months for patients receiving placebo (HR = 0.686; 95% CI: [0.566, 0.833], p = 0.0001). The time to opiate use result was supported by a delay in patient reported pain progression favoring the ZYTIGA arm.”

“Time to degradation in the FACT-P (Total Score): Treatment with ZYTIGA decreased the risk of FACT-P (Total Score) degradation by 22% compared with placebo (p = 0.0028). The median time to degradation in FACT-P (Total Score) was 12.7 months in the ZYTIGA group and 8.3 months in the placebo group.”

Study 301:

“The proportion of patients with pain palliation was statistically significantly higher in the ZYTIGA group than in the placebo group (44% versus 27%, p = 0.0002). A responder for pain palliation was defined as a patient who experienced at least a 30% reduction from baseline in the BPI-SF worst pain intensity score over the last 24 hours without any increase in analgesic usage score observed at two consecutive evaluations four weeks apart. Only patients with a baseline pain score of ≥ 4 and at least one post-baseline pain score were analysed (N = 512) for pain palliation.”

“A lower proportion of patients treated with ZYTIGA had pain progression compared to patients taking placebo at 6 (22% versus 28%), 12 (30% versus 38%) and 18 months (35% versus 46%). Pain progression was defined as an increase from baseline of ≥ 30% in the BPI-SF worst pain intensity score over the previous 24 hours without a decrease in analgesic usage score observed at two consecutive visits, or an increase of ≥ 30% in analgesic usage score observed at two consecutive visits.”

“The time to pain progression at the 25th percentile was 7.4 months in the ZYTIGA group, versus 4.7 months in the placebo group.”

Jevtana/cabazitaxel

None

“Secondary endpoints include pain progression [assessed using the Present Pain Intensity (PPI) scale from the McGill-Melzack questionnaire and an Analgesic Score (AS)] and pain response (defined as 2-point greater reduction from baseline median PPI with no concomitant increase in AS, or reduction of ≥ 50% in analgesic use from baseline mean AS with no concomitant increase in pain).”

“There was no statistical difference between both treatment arms in pain progression and pain response.”

Xofigo/radium Ra 223 dichloride

None

“Health Related Quality of Life (HRQOL) was assessed in the phase III ALSYMPCA study using specific questionnaires: the EQ-5D (generic instrument) and the FACT-P (prostate cancer specific instrument). Both groups experience a loss of quality of life. Relative to placebo, the decline in quality of life was slower for Xofigo during the on-treatment period as measured by EQ-5D utility index score (−0.040 versus −0.109; p = 0.001), EQ-5D self-reported Visual Analogue health status scores (VAS) (−2.661 versus −5.860; p = 0.018) and the FACT P total score (−3.880 versus −7.651, p = 0.006) but did not reach published minimally important differences. There is limited evidence that the delay in loss of HRQOL extends beyond the treatment period.”

“The results from the phase III ALSYMPCA study regarding time to external beam radiation therapy (EBRT) for pain relief and fewer patients reporting bone pain as an adverse event in the Xofigo group indicate a positive effect on bone pain.”