Scott Tagawa, MD, MS, FACP, provides commentary on the results of TITAN, a phase III study of apalutamide in patients with mCSPC receiving androgen deprivation therapy.

Hi, my name is Scott Tagawa. I am a medical oncologist at Weill Cornell Medicine New York Presbyterian Hospital in New York.

At the ASCO 2021 virtual meeting, the TITAN investigators, led by Neeraj Agarwal, presented quality of life patient‑reported outcome information from the TITAN study, which looked at the addition of apalutamide or placebo to ADT for those with metastatic non‑castrate, or hormone‑sensitive or castration‑sensitive ‑‑ different terminology ‑‑ prostate cancer.

What we learned from the prior presentation in New England Journal of Medicine publication was that early apalutamide led to an overall survival advantage, as well as all the other essentially secondary outcomes, such as progression‑free, radiographic progression‑free, etc.

From that initial dataset, there also have been some publications on quality of life, basically saying that, with early data, time to pain deterioration was better with apalutamide and no major deterioration in the quality of life measures.

What was updated at ASCO 2021, and actually part of a recent Journal of Clinical Oncology publication, were updated data. The publication included updated overall efficacy data, basically showing that the overall survival advantage was maintained.

Then, when an analysis accounting for crossover to apalutamide, that was maintained in the intent to treat analysis. When you account for crossover, it was even bigger.

What was presented by Dr. Agarwal at ASCO 2021 was a patient‑reported outcome quality of life follow‑up. This was longer follow‑up than their initial publication and presentation. Basically, the bottom line, which is important to know, that despite adding a more intense AR pathway‑targeted treatment ‑‑ so two drugs versus one ‑‑ there was no change in the patient‑reported outcomes.

The addition helped patients in terms of prolonging progression and prolonging death ‑‑ time to progression or death as well ‑‑ but did not result in worsening of patient‑reported outcomes in quality of life, in really any of the domains. I think that is important piece to have.

Secondly, there has been a number of different studies with a number of different drugs ‑‑ docetaxel, abiraterone, apalutamide, enzalutamide ‑‑ multiple randomized phase III trials. Most of these were published in either New England Journal or Lancet, so high‑impact journals.

It looks like these therapies, despite huge differences in overall survival ‑‑ as well as pretty much hitting every single secondary endpoint ‑‑ have not fully penetrated at the US‑treating population, for whatever reason.

There were a couple of initial looks at datasets, and at ASCO 2021, there were three additional datasets looking at different populations, really based on different insurances. What I would take from that are twofold.

Most importantly, there is a huge percentage of the patient population that are not getting intensified therapy. Intensified therapy is an additional drug that leads to an improvement in progression‑free and overall survival, without generally detriments in quality of life.

Early studies pointed towards about 80 percent not getting that therapy. Now, the additional ones, maybe it is getting closer to half, but it is still a problem, so we really need to educate the community.

I think there is a small fraction of patients, particularly with recurrent patients, rather than those presenting with metastatic, and with a lot of comorbidities that are maybe not right for additional therapy. Certainly, it is way more than half the patients, so we need to get that message out.