Latitude Trial

Background

Phase III double-blind, placebo-controlled RCT; 1199 newly diagnosed, treatment-naive metastatic castration-sensitive high-risk prostate cancer patients. High risk defined by ≥2 of 3: Gleason ≥8, ≥3 bone lesions, measurable visceral metastasis.

Interventions and follow up

Arm A: ADT + abiraterone 1000mg daily + prednisone 5mg daily.
Arm B: ADT + placebo.
Primary endpoints: OS and radiographic PFS.
mFollow up: 30.4mo (primary analysis); 51.8mo (final analysis).

Results

OS rate (interim): 66% vs 49%, arm A vs B; HR 0.62, 95%CI 0.51–0.76; P<.001.
mPFS: 33.0mo vs 14.8mo, arm A vs B; HR 0.47, 95%CI 0.39–0.55; P<.001.
mOS (final, 51.8mo): 53.3mo vs 36.5mo, arm A vs B; HR 0.66, 95%CI 0.56–0.78; P<.001.

Adverse events

Overall: Grade 3–4 events 63% vs 48% (arm A vs B); discontinuation 12% vs 10%.
Mineralocorticoid/cardiac: Hypertension 20% vs 10%; hypokalemia 10% vs 1%.

Conclusions

Abiraterone + prednisone added to ADT significantly improved OS and radiographic PFS in newly diagnosed, high-risk metastatic castration-sensitive prostate cancer versus ADT alone.

Key Limitations

Enrolled only high-risk mCSPC, limiting generalizability to low-volume/low-risk disease; placebo comparator predates docetaxel intensification, so does not address abiraterone-versus-chemotherapy or triplet sequencing.

Clinical Context

FDA approved abiraterone for high-risk mCSPC in 2018. Together with STAMPEDE, LATITUDE established ADT + abiraterone as a standard first-line option in ASCO/ESMO guidelines for metastatic castration-sensitive prostate cancer.

References

Karim F et al, NEJM, 2017; PMID: 28578607
Fizazi K et al. Lancet Oncol, 2019; PMID:30987939