Previous results from the LATITUDE trial have shown that adding abiraterone (Zytiga, Janssen) and prednisone to androgen deprivation therapy (ADT) improves overall survival when compared with ADT alone in men with newly diagnosed, high-risk metastatic, castration-naive prostate cancer.
Now a new analysis shows that the combination treatment also consistently improves pain, fatigue, and overall quality of life.
The new results were published online January 8 in the Lancet Oncology.
“If a treatment improves survival but negatively affects patient-reported outcomes (PROs) and health-related quality of life (HRQOL), it might not ultimately be beneficial to patients,” observes editorialist David Penson, MD, University Medical Center, Nashville, Tennessee, in an accompanying commentary.
“When the results of this analysis are considered in combination with the overall survival data from the LATITUDE trial, clinicians should feel assured that this regimen will benefit patients with metastatic castration-naive prostate cancer,” he adds.
The study authors, led by Kim Chi, MD, associate director, clinical research, Vancouver Prostate Centre, British Columbia, Canada, agree, and go even further in their comments. “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 a new standard-of-care option for patients with metastatic castration-naive prostate cancer,” they state.
Study Details
In the LATITUDE study, 597 patients were randomly assigned to receive ADT plus abiraterone acetate, at a dose of 1000 mg a day, and prednisone, 5 mg a day, while another 602 patients received ADT plus placebo.
“Patients in the ADT plus abiraterone acetate and prednisone group received a median of 25 treatment cycles…during a median follow-up of 30.9 months,” the study investigators note.
For the ADT plus placebo group, patients received a median of 15 cycles during a median follow-up of 29.7 months, they add.
Data were collected by way of electronic tablet devices during clinic visits on day 1 of cycle 1 through cycle 3, monthly during cycles 4 through to 13, and then every other month until the end of treatment.
Both PRO data and HRQOL were assessed by using a variety of symptom scores, including the Brief Pain Inventory-Short Form (BPI-SF); the Brief Fatigue Inventory; the Functional Assessment of Cancer Therapy Prostate Scale (FACT-P); and the EuroQol, 5-dimensions, 5-levels questionnaire (EQ-5D-5L).
On almost every comparison, men assigned to additional abiraterone acetate plus prednisone scored more favorably than men assigned to ADT plus placebo, as shown in table below. The only measure that did not significantly differ between the two groups was the median time to average pain progression, which was similar in both groups.
Table. Significant Differences in Measures of Pain, Fatigue, and Deterioration
| Measure | ADT + Abiraterone + Prednisone (mo) | ADT + Placebo (mo) | P Value |
|---|---|---|---|
| Median time to worst pain intensity progression | 11.07 | 5.62 | <.001 |
| Median time to pain interference progression | 6.5 | 3.7 | <.001 |
| Median time to fatigue interference progression | 31.3 | 9.2 | <.0001 |
| Median time to worst fatigue intensity | 18.4 | 6.5 | .001 |
| Median time to deterioration (FACT-P total score) | 12.9 | 8.3 | .032 |
“Mean changes from baseline in worst pain intensity, pain interference, and average pain progression improved with ADT plus abiraterone acetate and prednisone compared with ADT plus placebos at most time points evaluated,” the investigators observe. In addition, the “mean change in score was improved in the ADT plus abiraterone acetate and prednisone group as early as cycle 2 and maintained through cycle 33 for all BPI-SF measurements examined except at two data points: cycle 3 for average pain progression and cycle 25 for pain interference.”
Data collected on the EQ-5D-5L score also showed that patients in the ADT plus abiraterone acetate and prednisone group enjoyed better general health than those in the ADT plus placebo group and that improvements persisted throughout the study, the researchers also observe.
“The fact that the combination of ADT plus abiraterone acetate and prednisone appears to improve PROs over time supports its use in men with metastatic castration-naive prostate cancer,” Dr Penson comments in the editorial.
In contrast, the study authors note, “median time to deterioration of functional, emotional, and social and family wellbeing did not differ significantly between treatment groups”—not surprising, they suggest, because these aspects of life are less dependent on disease status and treatment.
But Which Drug to Add First?
Commenting further in his editorial, Dr Penson also points out that results from not only the LATITUDE trial but also the CHAARTED study, in which chemotherapy with docetaxel was added to ADT, showed an overall survival advantage for the group that added the drug to ADT when compared with ADT alone.
“Therefore, the question is no longer whether to add one of these agents to ADT for patients with castration-naive prostate cancer, but rather which to add first,” Dr Penson states.
Given that both studies suggest that each of the combinations are equally efficacious, with similar median overall survival rates, “clinicians will need to use other criteria for clinical decision making,” Dr Penson observes.
These criteria should include both the cost of treatment and how each regimen affects overall quality of life.
In this regard, docetaxel appears to be initially less costly than abiraterone acetate.
“However, docetaxel is associated with a higher incidence of adverse events during the immediate treatment period, which might have a deleterious effect on HRQOL in the long term, resulting in added treatment costs,” Dr Penson argues.
Thus, physicians may be forced to consider both data from quality-adjusted life-years as well as the cost-effectiveness of each of the two regimens to help them decide which combination to use for each patient.
Although studies addressing these issues are yet to be done, these PRO results from the LATITUDE trial “represent an important first step in this direction,” Dr Penson concludes.
Dr Chi reports having received grant funding from Janssen as well as grants and personal fees from Astellas, Bayer, and Sanofi, Essa and Roche, and Dr Chi’s institution received funding from Janssen for the conduct of the study. Disclosures for other coinvestigators are listed in the published article.Dr Penson reports that he has received grants, personal fees, and nonfinancial support from Astellas; personal fees from Janssen, grants, and nonfinancial support from Medivation; and grants, personal fees, and nonfinancial support from Dendreon, outside of the submitted work.
Lancet Oncol. Published online January 8, 2018. Abstract, Editorial
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