PROs and HRQoL among patients participating in the LATITUDE trial


A newly published paper in The Lancet Oncology has provided early data from the LATITUDE trial on patient-reported outcomes (PROs) and health-related quality of life (HRQoL) for men with newly diagnosed, high-risk, metastatic, castration-naive prostate cancer.

We have previously discussed, at some length, the clinical outcomes data from this trial, as were reported at the annual meeting of ASCO last year and simultaneously published in the New England Journal of Medicine.

The new paper by Chi et al. now addresses the degree to which differing treatments used in the LATITUDE trial may have benefited patients (or not) in terms of improvements in their quality of life over the course of the study from February 2012 through October 2016.

This is a complex paper, and so we are going to focus on the basic results derived from a series of questionnaires completed by participating patients at various times during the course of the study.

In 2013 and 2014 the LATITUDE trial enrolled 1,199 patients who were randomized to treatment with

  • Either standard ADT + abiraterone acetate (Zytiga) + predisone (Arm A; n = 597)
  • Or standard ADT + two placebos — one instead of the abiraterone and one instead of the prednisone (Arm B; n = 602)

Here are the basic results related to PROs and HRQoL:

  • Average (median) follow-up times were
    • 30.9 months for patients in  Arm A
    • 29.7 months for patients in Arm B
  • Average (median) time to deterioration of functional status, as measured using  a questionnaire that measures the Functional Assessment of Cancer Therapy Prostate (FACT-P) score was
    • 12.9 months for patients in Arm A
    • 8.3 months for patients in Arm B
    • Hazard ratio (HR) = 0.85; p = 0.032
  • Average (median) time to worst pain intensity progression assessed by the Brief Pain Inventory—Short Form (BPI-SF) score was not reached in either group.
  • Average (median) time to worst fatigue intensity was also not reached in either group.
  • There were indications that some subsets of patients in Arm A did better than comparable patients in Arm B with respect to both worst pain intensity progression and worst fatigue intensity.

The “New” Prostate Cancer InfoLink believes that all such data are helpful to patients and to their physicians as regards treatment decisions. However, they do need to be interpreted with considerable caution.

We know from the original reports of data from the LATITUDE trial that men in Arm A of this trial were exposed to significantly higher risk for Grade 3 to 5 adverse events (observed in 47 percent of patients, with 9 Grade 5 events) as compared to those in Arm B (observed in 33 percent of the patients, with 3 Grade 5 events).

We also know that there are inherent, well-understood problems associated with the long-term use of corticosteroid therapy (i.e., the prednisone used in Arm A of this trial).

The question that patients (and hopefully their doctors) are going to need to ask themselves is whether relatively small improvements in quality of life are worth the additional risks inherent in treatment with the combination of  standard ADT + abiraterone acetate + prednisone as compared to standard ADT alone. There is no simple answer to this question at this time. It is going to be a matter of individual choice.

We would emphasize, for those who do not understand this, that a Grade 5 adverse event in a clinical trial like this means that the patient died from that adverse event. In other words, one’s risk of dying from an adverse event in Arm A of this trial was three times higher than one’s risk of dying from an adverse event in Arm B.

Perhaps a better way to look at the data from the LATITUTE trial is to consider whether the significant overall, survival benefit of being treated in Arm A as opposed to Arm B is worth the risk associated with an increase in side effects. The apparently relatively small improvements in quality of life would seem to this commentator to be a small additional benefit by comparison, but not one that would significantly impact his decision about the type of treatment.

 

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