Medicine Matters oncology

I am going to discuss the results of the SWOG 1216 Trial in patients with metastatic castration-sensitive prostate cancer, which I had the honor of presenting as a representation in the 2021 American Society of Clinical Oncology meeting. In this clinical trial, more than 1,300 patients from across the United States from academic medical centers, from community medical centers were randomized to standard androgen-deprivation therapy plus TAK-700, a novel drug which inhibits extragonadal testosterone production versus androgen-deprivation therapy plus bicalutamide. The primary endpoint of the trial was overall survival. Secondary endpoints were progression-free survival and PSA response rates, along with assessment of safety.

The study reported earlier this year, and we presented the data in an ASCO meeting. What we saw was very intriguing. Progression-free survival was significantly improved in line with pretty much all contemporary clinical trials, with a 42% reduction in risk of progression or death. PSA responses were significantly higher in patients who received TAK-700 over bicalutamide, and we know that PSA response at seven month are a known, validated intermediate surrogate for overall survival. However, very interestingly, despite an 11-month improvement in overall survival in TAK-700 arm and with a P-value of 0.040 and a hazard ratio of 0.86 favoring TAK-700, it did not meet the predefined criteria for statistical significance, which was very intriguing and unlike all other contemporary trials recently presented.

So we looked back. We went back and looked at the treatment received in the control arm after patients had disease progression on the SWOG 1216 clinical trial. And we noticed that a very high number of patients, 77% of patients, had received life-prolonging therapy after they discontinued their participation in the SWOG 1216 trial in the control arm. And this is the highest-ever reported post-protocol receipt of life-prolonging therapy in patients who received treatment with standard androgen-deprivation therapy.

I don't think this level of receipt of life-prolonging therapy has been reported in any clinical trial where patients were receiving only standard androgen-deprivation therapy in the control arm. And I think that led to the highest-ever reported survival of the controller arm at 70 months. So even the TAK-700 resulted in an overall survival of 81 months. The controller arm did much better than expected.

We also went back and looked at the comparison of the control arm with SWOG-9346 trial, which compared androgen-deprivation therapy in an intermittent fashion versus continuous fashion, where the median arm, median control-arm survival was 46 months. And this trial was reported in 2013.

So within 10 years, the median arm survival, where patients are receiving androgen-deprivation therapy plus/minus bicalutamide, has improved from 46 months to 70 months, adding this happened because of the tremendous advancements in the setting of metastatic castrated-resistant prostate cancer.

So these results highlight two things-- number one, the great news for our patients, that the survival has improved tremendously over the last 10 years, and second, what the access to these life-prolonging therapies can make happen. So these patients who are on the control arm-- almost 80% of patients had access to life-prolonging therapy in the castrated-resistant prostate-cancer setting. And when they received these therapies, they survive much longer. So I think this is great news for our patients.