Alexandra Sokolova, MD, outlines TRIPLE-SWITCH trial in mCSPC

In this video, Alexandra Sokolova, MD, an assistant professor of medicine in the division of hematology/medical oncology at Oregon Health & Science University in Portland, discusses the rationale and design of the TRIPLE-SWITCH trial, a phase 3 study evaluating whether adding docetaxel to ongoing androgen-deprivation therapy (ADT) plus an androgen-receptor pathway inhibitor (ARPI) can improve outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) who exhibit suboptimal prostate-specific antigen (PSA) responses.

Sokolova explains that treatment for mCSPC has progressed from ADT alone to combinations that include docetaxel, ARPIs, or both. Although triplet therapy (ADT + docetaxel + ARPI) has shown benefit, it has never been directly compared with the commonly used doublet of ADT + ARPI. TRIPLE-SWITCH aims to address this evidence gap, focusing specifically on patients whose PSA responses to standard therapy predict poorer outcomes.

Hormone-sensitive prostate cancer is highly heterogeneous: Some patients progress within a year, whereas others remain sensitive for many years. Across multiple trials—including TITAN (apalutamide [Erleada]), LATITUDE (abiraterone acetate [Zytiga]), and ARCHES (enzalutamide [Xtandi])—PSA levels at 6 to 12 months have been strongly prognostic. Patients failing to reach a PSA ≤0.2 ng/mL have significantly worse survival, with median overall survival around 35 months. Because this subgroup is more likely to develop early castration resistance, Sokolova argues that treatment intensification is warranted before progression occurs.

Docetaxel is emphasized as an appealing option: it is inexpensive, widely available, well-understood, and generally tolerable, especially when used earlier in the disease course. TRIPLE-SWITCH tests whether adding 6 cycles of docetaxel during the hormone-sensitive phase—rather than waiting for castration-resistant disease—can meaningfully extend survival.

Eligible patients must have metastatic disease, an initial PSA ≥5 ng/mL, and a PSA ≥0.2 ng/mL at enrollment after at least 6 to 12 months of ADT and 4 months of ARPI therapy. Participants are randomly assigned to continue standard therapy alone or receive added docetaxel. The primary end point is overall survival, with secondary end points including PSA response metrics, progression measures, PSA kinetics, and several circulating tumor DNA assessments to help identify which patients benefit most.