Survival Outcomes for Sequential Use of New Agents in Metastatic Castration-Resistant Prostate Cancer

[TNCanuck]

Source: practiceupdate.com/C/97560/56

TAKE-HOME MESSAGE

Although there are many new treatments for metastatic castration-resistant prostate cancer (MCRPC), including cabazitaxel, enzalutamide, and abiraterone, the optimal sequence is poorly understood. In this retrospective analysis of outcomes from published studies, the authors evaluated individual survival outcomes of 1099 men with MCRPC after docetaxel chemotherapy and either cabazitaxel or a new hormone agent (enzalutamide or abiraterone). From the start of the second-line therapy, there was no difference in cumulative overall survival across agents. However, in patients who progressed after 6 months, the median overall survival was longer in those who received cabazitaxel therapy as part of their therapy instead of back-to-back new hormone agents (29.5 vs 24.8 months; P=.03).

Urologists who treat MCRPC should be aware of differences in treatment agents. In patients who have persistent disease following docetaxel, urologists may wish to avoid back-to-back hormone agents, and, instead, consider integration of cabazitaxel.

– Michael H. Johnson, MD

INTRODUCTION

The sequential use of a number of new agents (NAs) have improved the overall survival (OS) of patients with metastatic castration-resistant prostate cancer whose disease progresses after docetaxel (DOC) treatment. The aim of this study was to assess the cumulative survival outcomes of different sequencing strategies by evaluating the individual data from published studies of patients treated with a post-DOC treatment sequence of 2 NAs.

PATIENTS AND METHODS

The patients' individual data were analyzed to investigate whether different sequencing strategies lead to differences in OS.

RESULTS

We analyzed the data of 1099 evaluable patients. Among the patients treated with a second-line new hormone agent (NHA), median OS from the start of third-line treatment was significantly longer in the patients treated with cabazitaxel (CABA) than in those treated with abiraterone acetate or enzalutamide. Median cumulative OS (cumOS) from the start of second-line treatment was 21.1 months in the patients who received NHA then NHA, 22.1 months in those who received NHA then CABA, and 21.0 months in those who received CABA then NHA. Among the patients with a second-line progression-free survival of ≥6 months, median cumOS was significantly longer in patients who received CABA-including sequences than in those treated with NHA then NHA sequences (29.5 vs. 24.8 months; P = .03).

CONCLUSION

Our findings suggest that the sequential use of NAs with different mechanisms of action improves cumOS regardless of the order in which they are administered, thus supporting the hypothesis of cross-resistance between the 2 NHAs.

[Pleroma]

Good to know - thanks.

[noahware]

It says "in patients who progressed after 6 months, the median overall survival was longer in those who received cabazitaxel therapy as part of their therapy instead of back-to-back new hormone agents (29.5 vs 24.8 months; P=.03)"

I keep wondering whenever I see a "survival benefit" expressed in terms of a difference of a few months of median overall survival: what is this aggregate survival advantage actually telling us about how different treatments really differentially help (or don't help, or even hurt) any individual man or any of a number of subgroups of men?

In light of not-very-dramatic survival differences, it seems like we end up facing the same reality: your mileage may vary, and we don't yet really have great ways of telling you why and when it will vary.

[Hidden in reply to noahware]

Noah, you do realize that the nearly 4.0 benefit includes men from vary stages of disease with varying, Gleasons and most important, co-morbidity (s)? In other words, guys who on their last legs or damn near close. It’s a mean score; not an average. And, in the trial cohort, if a guy two months in up and has a heart attack while sweating in 100 degrees dies, he is counted along with the guy who is walking around 72 months out.

How you fare has no bearing on the trial cohort. It shows a marked improvement and really that is all you need to know. My best advice after dealing with metastatic PCa, is to concentrate on staying positive and quit worry about that which you have no control.

Keep killing the bastard. And, enjoy life.

Gourd Dancer

[Jdbnord]

sammamish