Weill Cornell Medicine, New York, NY
Vincenza Conteduca , Clara Oromendia , Panagiotis J. Vlachostergios , Amy Hackett , Charlene Thomas , Aidan Case , Jyothi Manohar , Kenneth Eng , Andrea Sboner , Karla V. Ballman , Olivier Elemento , David M. Nanus , Himisha Beltran , Scott T. Tagawa
Background: PSMA targeted therapy has recently emerged as a promising approach for patients with advanced prostate cancer. However, there is still a need for reliable biomarkers that provide information about clinically meaningful outcomes and treatment responses. Methods: Baseline, treatment and outcomes data along with tumor whole-exome sequencing (WES) data were retrospectively evaluated in anti-PSMA-treated patients (pts). Statistical comparisons utilized Cox regression analysis and Kaplan-Meier method for association with overall/progression-free/survival (OS/PFS) and PSA response. Results: We analyzed 25 pts treated with PSMA targeted radionuclide therapies refractory to standard therapy. 15 received 177Lu-J591, 8 received 177Lu-PSMA-617, 1 received both, and 1 225Ac-J591. WES data (n=28) showed an incidence of AR, BRCA1, BRCA2, ATM alterations (copy number variations and point somatic mutations) in 71.4% (n=20), 11.1% (n=3), 29.6% (n=8), and 14.3% (n=4), respectively. Variables found with backward selection with AIC criterion for PFS and OS suggest significant clinical and molecular predictors of PFS/OS (Table). Conclusions: Knowledge of prognostic factors such as baseline narcotic use and ALP, and BRCA1/BRCA2 and TP53 alterations may have potential clinical utility in patients being considered for anti-PSMA targeted radionuclide therapies. Validation of these findings in larger prospective trials is warranted.
Backward stepwise selection for PFS | Backward stepwise selection for OS | ||||
---|---|---|---|---|---|
Variable | HR (95% CI) | P | Variable | HR (95% CI) | P |
Narcotic use | 0.28 (0.08,0.91) | 0.035 | Baseline ALP | 1.02 (1.00, 10.3) | 0.024 |
Baseline ALP | 1.02 (1.01,1.03) | 0.003 | BRCA2 alteration | 0.09 (0.01,0.91) | 0.041 |
BRCA1 alteration | 0.02 (0.0,0.32) | 0.004 | |||
BRCA2 alteration | 0.26 (0.08,0.85) | 0.026 | |||
TP53 alteration | 4.82 (1.24,18.74) | 0.023 |
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