RT Journal Article
T1 Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study.
A1 Poveda, Andres
A1 Lopez-Reig, Raquel
A1 Oaknin, Ana
A1 Redondo, Andres
A1 Rubio, Maria Jesus
A1 Guerra, Eva
A1 Fariñas-Madrid, Lorena
A1 Gallego, Alejandro
A1 Rodriguez-Freixinos, Victor
A1 Fernandez-Serra, Antonio
A1 Juan, Oscar
A1 Romero, Ignacio
A1 Lopez-Guerrero, Jose A
K1 endometrial cancer
K1 genomic instability
K1 lurbinectedin
K1 olaparib
K1 ovarian cancer
AB We hypothesized that the combination of olaparib and lurbinectedin maximizes DNA damage, thus increasing its efficacy. The POLA phase 1 trial established the recommended phase 2 dose of lurbinectedin as being 1.5 mg (day 1) and that of olaparib as being 250 mg/12 h (days 1-5) for a 21-day cycle. In phase 2, we explore the efficacy of the combination in terms of clinical response and its correlation with mutations in the HRR genes and the genomic instability (GI) parameters. Results: A total of 73 patients with high-grade ovarian (n = 46), endometrial (n = 26), and triple-negative breast cancer (n = 1) were treated with lurbinectedin and olaparib. Most patients (62%) received ≥3 lines of prior therapy. The overall response rate (ORR) and disease control rate (DCR) were 9.6% and 72.6%, respectively. The median progression-free survival (PFS) was 4.54 months (95% CI 3.0-5.2). Twelve (16.4%) patients were considered long-term responders (LTR), with a median PFS of 13.3 months. No clinical benefit was observed for cases with HRR gene mutation. In ovarian LTRs, although a direct association with GI and a total loss of heterozygosity (LOH) events was observed, the association did not reach statistical significance (p = 0.055). Globally, the total number of LOHs might be associated with the ORR (p =0.074). The most common grade 3-4 toxicities were anemia and thrombocytopenia, in 6 (8.2%) and 3 (4.1%) patients, respectively. Conclusion: The POLA study provides evidence that the administration of lurbinectedin and olaparib is feasible and tolerable, with a DCR of 72.6%. Different GI parameters showed associations with better responses.
SN 2072-6694
YR 2022
FD 2022-02-12
LK http://hdl.handle.net/10668/20873
UL http://hdl.handle.net/10668/20873
LA en
DS RISalud
RD Apr 20, 2025