Men with newly diagnosed mCRPC in the global LATITUDE trial reported clinical improvements in pain progression, prostate cancer symptoms, fatigue, functional decline, and overallHR-QOL following treatment with abiraterone acetate plus prednisone.
Kim N. Chi, MD
Kim N. Chi, MD
Men with newly diagnosed metastatic castration-naïve prostate cancer in the global LATITUDE trial reported clinical improvements in pain progression, prostate cancer symptoms, fatigue, functional decline, and overall health-related quality of life (HR-QOL) following treatment with abiraterone acetate (Zytiga) plus prednisone.1
At a median follow-up of 30.9 months, mean changes from baseline in worst pain intensity, pain interference, and average pain progression improved with androgen deprivation therapy (ADT) plus abiraterone and prednisone compared with ADT plus placebo. The same was true for changes from baseline in worst fatigue intensity, fatigue interference mean scores, and general health status scores.
“In this analysis of patient-reported outcomes, the combination of ADT plus abiraterone acetate and prednisone provided clinically and statistically significant improvements compared with ADT plus placebos by delaying time to worst pain intensity and pain interference, as well as worst fatigue intensity and fatigue interference, and by prolonging time to HRQOL deterioration as per the Functional Assessment of Cancer Therapy-Prostate total score in patients with newly diagnosed, high-risk metastatic castration-naive prostate cancer,” corresponding author Kim N. Chi, MD, medical director, Clinical Trials Unit, BC Cancer Agency—Vancouver Centre, and coinvestigators wrote.
“The improvements in both survival and HRQOL shown in the LATITUDE trial suggest that treatment with ADT plus abiraterone acetate and prednisone could be considered as a new standard- of-care option for patients with metastatic castration-naive prostate cancer,” added Chi et al.
In LATITUDE, 1199 newly diagnosed patients with high-risk metastatic prostate cancer were randomly assigned to abiraterone, prednisone, and ADT (n = 597) or ADT and placebo (n = 602) from February 2013 to December 2014. Patients in the experimental arm received 1000 mg of abiraterone and 5 mg of prednisone daily.
Eligible patients had not previously received ADT therapy and had at least 2 of 3 risk factors: Gleason score greater than or equal to 8, measurable visceral metastases, or 3 or more bone lesions. Men in the study had either a positive bone scan or a metastatic lesion at the time of diagnosis on CT or MRI.
Results from LATITUDE showed that the abiraterone regimen reduced the risk of death by 38% compared with ADT and placebo in men with high-risk, metastatic castration-sensitive prostate cancer. The median overall survival was not reached with abiraterone versus 34.7 months with placebo (HR, 0.62; 95% CI, 0.51-0.76; P <.001).
The radiographic progression-free survival with abiraterone was 33.0 months compared with 14.8 months for ADT alone, representing a 53% reduction in the risk of progression or death (HR, 0.47; 95% CI, 0.39-0.55; P <.001). The overall survival rate at 3 years was 66% in the abiraterone group versus 49% with ADT alone.
Patient-reported outcome (PRO) data were collected at the clinical sites during screening and before any other visit on day 1 of cycles 1 to 3, monthly during cycles 4 to 13, and then every 2 months until the end of treatment. Patients completed the Brief Pain Inventory—Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol (EQ-5D-5L) questionnaires.
Median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either group (HR, 0.63; 95% CI, 0.52-0.77; P <.0001). Neither group reached median time to worst fatigue intensity (HR, 0.65; 95% CI, 0.53-0.81; P = .0001).
Median time to deterioration of functional status was 12.9 months (95% CI, 9.0-16.6) in the abiraterone arm versus 8.3 months (95% CI, 7.4-11.1) in the control arm (HR, 0.85; 95% CI, 0.74-0.99; P = .032).
Median time to worst fatigue intensity was not reached in either arm (HR, 0.65; 95% CI, 0.53-0.81; P = .0001), nor was median time to fatigue interference progression (HR 0.59; 95% CI, 0.47-0.75; P <.0001). Abiraterone was associated with improvements in worst fatigue intensity and fatigue interference mean scores as early as cycle 5 and maintained through cycle 33 except at cycle 27 for worst fatigue intensity and cycles 19 and 27 for fatigue interference.
Writing in an accompanying editorial David F. Penson, MD, department of Urologic Surgery Health Policy and Medicine and Center for Surgical Quality and Outcomes Research, Vanderbilt University Medical Center, said that these results showing that abiraterone appears to improve PROs over time supports its use in men with metastatic castration-naive prostate cancer.2
He added that these findings are vital as the ADT/abiraterone/prednisone combination becomes more popular. Physicians used ADT for years under the assumption that the treatment had little or no negative effect on PROs or HRQOL, only to learn later that it can have serious negative effects on HRQOL, cognition, and other clinical outcomes.
“If the effect of ADT on PROs and HRQOL had been known earlier, perhaps clinicians would have been more cautious about the use of this therapy in discretionary settings,” Penson wrote. “Understanding the effect on PROs and HRQOL of adding abiraterone and prednisone to ADT might help to identify those patients who are most likely to benefit from this regimen, and result in a more judicious use of available prostate cancer therapies going forward.”
Based on the LATITUDE findings, Janssen Biotech, the manufacturer of abiraterone, submitted a supplemental new drug application to the FDA in September 2017 for the use of abiraterone in combination with prednisone and ADT for high-risk patients with metastatic hormone-naïve prostate cancer or newly-diagnosed metastatic hormone-sensitive prostate cancer.