ESMO Congress 2026

Cabazitaxel is a novel tubulin-binding taxane whose position in metastatic castration-resistant prostate cancer (mCRPC) after docetaxel was established by a randomised open-label phase 3 trial comparing cabazitaxel 25 mg/m² plus prednisone versus mitoxantrone plus prednisone in patients progressing after docetaxel-based treatment, with overall survival as the primary endpoint ^[1]. The EAU-ESTRO-SIOG guidelines list cabazitaxel alongside abiraterone, enzalutamide and radium-223 as approved second-line options for mCRPC after docetaxel ^[3]. Notably, the randomised phase 2 TheraP trial compared 177Lu-PSMA-617 head-to-head with cabazitaxel in mCRPC patients for whom cabazitaxel was the next appropriate standard treatment ^[6], and the single-centre single-arm phase 2 LuPSMA trial examined 177Lu-PSMA-617 in patients progressed after standard treatments including taxane chemotherapy and second-generation anti-androgens ^[5], together framing an established either-or landscape between radioligand therapy and taxane chemotherapy.

Two pieces of information at this meeting relate to cabazitaxel, with LuCAB as the main thread: combination 177Lu-PSMA-617 plus cabazitaxel in mCRPC post-docetaxel and post-ARPI, 35 patients, accepted by The Lancet Oncology. No DLTs were observed during dose escalation; the RP2D was established as cabazitaxel 20 mg/m² + 7.4 GBq LuPSMA; G3 treatment-related adverse events were 24%, with no G4/5. In the RP2D cohort (n=26), PSA50 was 73%, rPFS 10.9 months and OS 16.5 months, in an unfavourable cohort (29% M1c). The investigators' rationale is that adding taxane chemotherapy may overcome heterogeneous PSMA expression and act as a radiosensitiser.

The other is the PROFIT real-world study in Spain (n=224): 59% of patients received Ra-223 within the first two mPC lines and 41% at ≥3L; earlier Ra-223 was associated with longer OS (12.4 vs 9.3 months, p=0.024); ≥5 injections were strongly associated with longer OS (14.1 vs 7.1 months, p<0.001), and 62.5% completed 5–6 injections; 48.7% received subsequent mCRPC therapy, most commonly cabazitaxel or docetaxel — meaning that in routine practice cabazitaxel frequently serves as the key chemotherapy bridging step after Ra-223.

In terms of incremental value, LuCAB moves beyond TheraP's framing of LuPSMA and cabazitaxel as parallel options ^[6] to explore simultaneous combination, and delivers efficacy signals in a poor-prognosis cohort with manageable tolerability; PROFIT suggests that maintaining Ra-223 treatment continuity and appropriately sequencing subsequent chemotherapy (often cabazitaxel or docetaxel) is associated with improved survival. The limitations are equally clear: LuCAB is single-arm with a small sample (35 patients; 26 in the RP2D cohort), its efficacy data come from the RP2D cohort, and the investigators themselves note that randomised trials are needed to answer whether chemotherapy and LuPSMA should be combined or sequenced; PROFIT is real-world observational data, and its OS differences represent associations rather than causal conclusions.