Valentina Boni, MD, PhD, Discusses Activity of Lurbinectedin in Pretreated BRCA-Associated Breast Cancer

Valentina Boni, MD, PhD, spoke about the rationale behind using lurbinectedin monotherapy for pretreated BRCA1/2-associated metastatic breast cancer.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Valentina Boni, MD, PhD, of the director of clinical research and principal investigator at NEXT Oncology Madrid in Spain an Early Drug Development Unit at the Universitary Hospital Universitario Quirónsalud Madrid as well as director and principal investigator at NEXT Oncology Madrid in Spain, about results in a cohort of patients with pretreated BRCA 1/2-associated metastatic breast cancer (n = 21) who were treated on a phase 2 basket study (NCT02454972) of lurbinectedin (Zepzelca) monotherapy.1 Patients experienced a median progression-free survival of 4.1 months (95% CI, 2.3-6.5) and a median overall survival of 16.1 months (95% CI, 8.7-not reached).

Transcript:

Lurbinectedin is a selective inhibitor of the oncogenic transcription that leads to cell apoptosis and shows antitumor activity against homologous recombination repair–deficient cell lines. Lurbinectedin has already been approved as a monotherapy in metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.2 A prior phase II study in patients with pretreated, BRCA1/2-mutated, metastatic breast cancer treated with lurbinectedin demonstrated antitumor activity.3 In addition, we have a phase 2 study in which patients with BRCA1/2-mutated pretreated metastatic breast cancer who were treated with lurbinectedin [experienced a response rate that was] higher in comparison with arm B where patients were [unselected]. Based on these previous results and the preclinical data that we have, we decided to include a new arm in this phase 2 basket trial in which we explore the activity of lurbinectedin in [patients with] metastatic breast cancer harboring BRCA mutations.

In [the pretreated BRCA1/2] arm of the phase 2 basket trial, we included 21 women with metastatic breast cancer harboring BRCA mutations after 2 prior lines of therapy, including platinum compounds in more than 40% of patients. In addition, 5 patients were previously treated with PARP inhibitors. Interestingly, we have seen an overall response rate of 28.6% [95% CI, 11.3%-52.2%] with a median duration of response of 8.6 months, and a clinical benefit rate of 57.1% [95% CI, 34.0%-78.2%]. These results are remarkable, especially taking into account that this is a pretreated population, including patients who are resistant to prior platinum compounds and PARP inhibitors.

References

  1. Boni V, Pistilli B, Brana I, et al. Lurbinectedin in patients with pretreated BRCA1/2-associated metastatic breast cancer: Results from a phase II basket study. J Clin Oncol. 40(suppl 16):1092. doi:10.1200/JCO.2022.40.16_suppl.1092
  2. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. News Release. FDA. June 15, 2020. Accessed July 8, 2022. https://bit.ly/3uugxkX
  3. Cruz C, Llop-Guevara A, Garber JE, et al. Multicenter phase II study of lurbinectedin in BRCA-mutated and unselected metastatic advanced breast cancer and biomarker assessment substudy. J Clin Oncol. 2018;36(31):3134-3143. doi:10.1200/JCO.2018.78.6558. Published correction appears in J Clin Oncol. 2018 Nov 20;36(33):3348. Published correction appears in J Clin Oncol. 2019 Feb 1;37(4):362