For those newly diagnosed with metastatic castration‑sensitive prostate cancer—which responds to lowered testosterone levels—the first treatment conversations can feel especially overwhelming. Questions about hormone therapy, chemotherapy, long‑term outcomes, and quality of life come at a time when clarity is desperately needed. At the University of Colorado Anschutz Cancer Center, medical oncologist Laura Graham, MD, is leading a national clinical trial designed to bring that clarity to thousands of patients and their care teams.
The Triple Switch clinical trial focuses on a question that has challenged oncologists for years: When should chemotherapy be added to the current standard of care? The answer could reshape treatment guidelines nationwide. As Graham puts it, “One of the hardest conversations I have is whether chemotherapy should be added upfront. Right now, I can’t give good information about who the right people are to get chemotherapy or how much benefit it actually adds.”
The study aims to change that by focusing on a specific group whose treatment responses often remain uncertain, specifically patients whose PSA levels do not fall to zero after initial therapy with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI). “We really hope patients get that PSA down to zero,” she explains. “But if they don’t, then maybe this treatment will help them live longer. And if it doesn’t, we want to know that, too, so we’re not adding unnecessary side effects.”
Why This Trial Matters
For years, triplet therapy - ADT, ARPI, and docetaxel chemotherapy - has been used in certain cases, but the evidence guiding who should receive chemotherapy remains inconsistent. Prior studies looked at combinations of ADT and chemotherapy, sometimes with ARPIs, but these trials occurred before ARPIs became standard practice. Because of that, researchers still don’t know how much benefit docetaxel brings on top of modern hormonal therapy.
“What we learned from earlier studies is that if you’re going to give chemotherapy, you need to give an ARPI with it,” Graham says. “But what we still don’t know is, if you’re already doing ADT and an ARPI, how much is the chemotherapy helping?” The Triple Switch trial directly targets that knowledge gap by studying men whose PSA responses suggest they may be at higher risk for faster disease progression.
For Graham, the trial represents a more thoughtful, personalized approach to prostate cancer treatment. “This isn’t a ‘whoever walks in the door gets the same thing’ kind of trial,” she says. “It’s asking, who are the people that truly benefit from adding chemotherapy at this moment?”
A Study Design Built Around Real‑World Care
Participants in the trial must have received six to 12 months of ADT and at least four months of an ARPI. If their PSA levels remain detectable, they are eligible for randomization to either continue with hormonal therapy alone or to receive six cycles of docetaxel chemotherapy.
The chemotherapy schedule mirrors standard clinical practice: an infusion every three weeks for six cycles. After treatment, both groups follow the same monitoring pattern—regular visits every three months, PSA checks, symptom reviews, and imaging when appropriate.
While the science behind the design is rigorous, Graham is equally proud of the study’s patient‑centered approach. “One of the really nice things about this trial is it allows virtual visits,” she says. After the chemotherapy phase, patients can complete many of their follow‑up appointments virtually, which is especially significant for those traveling from rural Colorado or neighboring states for specialty care. “If we can remove barriers—like unnecessary travel—more people can access clinical trials. That means better care and better outcomes.”
She also highlights that patients often do better on clinical trials because of the amount of oversight and support involved. “Even people in the standard‑of‑care arm of clinical trials have better outcomes,” she says. “There’s so much rigor, and it’s such a team‑based effort. It’s not just about the science—it’s the overall care.”
What the Trial Hopes to Learn
The primary goal of the Triple Switch trial is to determine whether adding chemotherapy helps people live longer. Graham acknowledges that talking about survival can feel daunting for patients, but it remains one of the outcomes patients care about most. “When you’re diagnosed with cancer, one of the most important things you’re worried about is how long you’re going to live,” she says.
Researchers are also watching how many patients achieve a deeper PSA response after adding chemotherapy, how long people remain on their first‑line therapy before switching to another treatment, how safe docetaxel is in this specific setting, and whether quality of life improves or declines with the addition of chemotherapy.
Graham notes that patients often feel strongly—sometimes anxiously—about whether they want chemotherapy. “Some people really don’t want it because they’re afraid of side effects,” she says. “Others hear their PSA hasn’t gone to zero and feel strongly that they want chemotherapy. But the truth is, we don’t know the right answer yet. That’s why this trial is so important.”
A Personal Commitment to Better Answers
Graham came to prostate cancer research somewhat by chance, but the field quickly became her passion. “I didn’t grow up thinking I’d spend all day thinking about prostates,” she jokes. But as a young trainee, she authored a review on androgen receptor signaling and found the biology “really interesting and complex.” She also found deep meaning in caring for patients facing some of the hardest moments of their lives. “If you can be present with people in their hardest moments and do that well, it’s incredibly meaningful.”
Ultimately, she hopes the Triple Switch trial brings clarity to a confusing decision point in metastatic prostate cancer treatment. “My job isn’t to tell someone what to do,” she says. “My job is to give them the right information so they can make a choice that aligns with their values. But it’s hard to do that if I don’t have the right information. I’m hoping this trial will give us that information.”
