PSMA and Beyond 2026: Chemotherapy versus PSMA Radioligand Therapy: The CCTG PR21 Trial

(UroToday.com) The 2026 PSMA & Beyond conference featured a clinical trial updates session and presentation by Dr. Francois Benard discussing the CCTG PR21 trial assessing chemotherapy versus PSMA radioligand therapy. ¹⁷⁷Lu-PSMA-617 prolongs radiographic progression free survival in taxane-naïve patients with metastatic castration resistant prostate cancer (mCRPC), when compared to an androgen receptor pathway inhibitor switch.¹In the PSMAfore trial, for ¹⁷⁷Lu-PSMA-617, the median radiographic progression free survival was 11.6 months, and the median overall survival was 24.5 months. Docetaxel is also a standard of care option in patients with mCRPC progressing after an androgen receptor pathway inhibitor. Outcomes with docetaxel after an androgen receptor pathway inhibitor in a recent phase III trial demonstrated a median radiographic progression free survival of 8.3 months and an overall survival of 19 months.² In the CCTG PR21 trial, the investigators aimed to compare these two treatment options for chemotherapy-naïve mCRPC patients progressing after androgen receptor pathway inhibitor therapy.

This was an open label, randomized, phase II trial that allowed for crossover between the two study arms. The key eligibility criteria were as follows:

Chemotherapy-naïve mCRPC progressing after an androgen receptor pathway inhibitor
PSMA PET positive disease (ie. uptake > liver)
- Excluded if >50% of extra-osseous lesions or >5 cm soft tissue lesion was PSMA negative
Adequate end organ function
Prior docetaxel for mHSPC permitted if ≥12 months prior

Eligible patients were randomized 1:1 to ¹⁷⁷Lu-PSMA-617 7.4 GBq IV every 6 weeks x 6 cycles versus docetaxel 75 mg/m² every 3 weeks x 12 cycles. The primary endpoint was radiographic progression free survival, with key secondary endpoints including:

Overall survival
Radiographic progression free survival 2
PSA decline
Adverse events
Patient-reported outcomes/quality-of-life
Correlative studies

The CONSORT diagram is illustrated below. There were 199 patients randomized to ¹⁷⁷Lu-PSMA-617 (n = 100) or docetaxel (n = 99). The median numbers of ¹⁷⁷Lu-PSMA-617 and docetaxel doses were 5 and 8, respectively. Fifteen patients discontinued docetaxel due to treatment related adverse events, compared to only one in the ¹⁷⁷Lu-PSMA-617 arm. Thirty-eight patients crossed over from ¹⁷⁷Lu-PSMA-617 to docetaxel versus 56 from docetaxel to ¹⁷⁷Lu-PSMA-617.

There was no difference in radiographic progression free survival between the two arms. The median radiographic progression free survival values were 8.6 and 10.7 months for the ¹⁷⁷Lu-PSMA-617 and docetaxel arms, respectively (HR 1.01, 95% CI 0.77–1.31; p = 0.51).

Disease response rates favored ¹⁷⁷Lu-PSMA-617:

PSA50 response: 36% versus 16% (p = 0.0015)
Complete or partial response: 16% versus 8% (p = 0.23)

Grade 3-4 treatment related adverse events were more common in the docetaxel arm (34% versus 13%). Two treatment related deaths were observed (sepsis, not otherwise specified), both of which were in the docetaxel arm. The most common adverse events in either arm were as expected for both treatments.

Radiographic progression free survival 2 favored patients initially randomized to the docetaxel arm (HR 1.40, 90% CI 0.77–1.31; p = 0.09).

Overall survival also favored patients initially randomized to the docetaxel arm (HR 1.64, 95% CI 1.14–2.35; p = 0.02). The median overall survival was 14.3 and 18.2 months, respectively, in favor of initial randomization to docetaxel.

The median SUV_meanwas prognostic, but not predictive for radiographic progression free survival. As seen below, patients with SUV_mean high disease had worse radiographic progression free survival outcomes, compared to SUV_meanlow disease, in both treatment arms. Furthermore, patients with SUV_meanhigh disease did not derive a preferential benefit from ¹⁷⁷Lu-PSMA-617 therapy, confirming that SUV_mean was not predictive in this setting.

Dr. Benard concluded his presentation discussing the CCTG PR21 trial assessing chemotherapy versus PSMA radioligand therapy with the following take-home points:

There was no difference in the primary endpoint of radiographic progression free survival between ¹⁷⁷Lu-PSMA-617 and docetaxel in patients with chemotherapy-naïve mCRPC progressing after an androgen receptor pathway inhibitor
Other endpoints favored ¹⁷⁷ Lu-PSMA-617:
- There was a higher proportion of patients with a PSA decline and measurable disease response
- Fewer grade ≥3 adverse events and treatment discontinuations due to adverse events were seen with initial ¹⁷⁷Lu-PSMA-617 randomization
PSMA PET median SUV_mean was prognostic, but not predictive, of radiographic progression free survival for ¹⁷⁷Lu-PSMA-617 and docetaxel
Overall survival was longer in patients initially randomized to docetaxel - this is possibly due to a higher treatment cross-over rate from docetaxel to ¹⁷⁷Lu-PSMA-617
Additional analyses with longer follow-up, patient reported outcomes, PSMA PET parameters, and serial ctDNA samples are planned

Presented by: François Bénard, MD, BC Cancer Research Institute, Vancouver, British Columbia, Canada

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 PSMA & Beyond Conference, Los Angeles, CA, Thurs, Mar 26 – Fri, Mar 27, 2026.

Related content: Chemo versus PSMA RLT "Presentation" - François Bérnard

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