JCO precision oncology · 2025
Olaparib in Patients With Solid Tumors With BRCA1/2 Alterations: Results From The Targeted Agent and Profiling Utilization Registry (TAPUR) Study.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Al Baghdadi Tareq, Rothe Michael, Mangat Pam K, Garrett-Mayer Elizabeth, Crysler Oxana V, Mileham Kathryn F, Farrington Laura Catherine, Adesunloye Bamidele, Dublis Stephanie A, Astsaturov Igor, Calfa Carmen J, Bleeker Jonathan, Khalil Maya, Thota Ramya, Cannon Timothy L, Alese Olatunji B, Gold Philip J, Hafez Navid, Baron Ari D, Meric-Bernstam Funda, Hobbs Evthokia, Marr Alissa S, Rueter Jens, Tawfik Bernard, Hinshaw Dominique C, Gregory Abigail, Grantham Gina N, Halabi Susan, Schilsky Richard L
Аннотация
PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of five cohorts of patients with BRCA1/2-mutated solid tumors treated with olaparib are reported: breast cancer (BC), biliary tract cancer (BTC), lung cancer (LC), uterine cancer (UC), and other solid tumors (histology-pooled [HP]).
METHODS: Eligible patients had advanced tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For histology-specific cohorts, Simon two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Cohorts that were closed before achieving the planned stage II sample size were analyzed using a one-sided exact binomial test. For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were objective response, progression-free survival, overall survival, duration of response or SD, and safety.
RESULTS: Patients with BC (n = 28), BTC (n = 19), LC (n = 25), UC (n = 15), or other advanced cancers (n = 32) with BRCA1/2 alterations were enrolled. The DC rates with one-sided 90% CI were 69% (55-100, P < .001), 50% (32-100, P = .0008), 41% (26-100, P = .0025), 47% (28-100, P = .0036), and 41% (29-100), respectively. The null hypothesized 15% DC rate was rejected for all cohorts. Thirty-six of 119 patients experienced treatment-related grade 3-4 adverse events (AEs) or serious AEs.
CONCLUSION: Olaparib met prespecified criteria to declare a signal of activity in patients with various advanced BRCA1/2-altered solid tumors.
METHODS: Eligible patients had advanced tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For histology-specific cohorts, Simon two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Cohorts that were closed before achieving the planned stage II sample size were analyzed using a one-sided exact binomial test. For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were objective response, progression-free survival, overall survival, duration of response or SD, and safety.
RESULTS: Patients with BC (n = 28), BTC (n = 19), LC (n = 25), UC (n = 15), or other advanced cancers (n = 32) with BRCA1/2 alterations were enrolled. The DC rates with one-sided 90% CI were 69% (55-100, P < .001), 50% (32-100, P = .0008), 41% (26-100, P = .0025), 47% (28-100, P = .0036), and 41% (29-100), respectively. The null hypothesized 15% DC rate was rejected for all cohorts. Thirty-six of 119 patients experienced treatment-related grade 3-4 adverse events (AEs) or serious AEs.
CONCLUSION: Olaparib met prespecified criteria to declare a signal of activity in patients with various advanced BRCA1/2-altered solid tumors.