American Association for Cancer Research
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Supplementary Table 3 from Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer

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posted on 2023-03-31, 22:25 authored by Tanya E. Keenan, Tianyu Li, Tuulia Vallius, Jennifer L. Guerriero, Nabihah Tayob, Bose Kochupurakkal, Janae Davis, Ricardo Pastorello, Rie K. Tahara, Leilani Anderson, Jake Conway, Meng X. He, Erin Shannon, Robert E. Godin, Peter K. Sorger, Alan D'Andrea, Beth Overmoyer, Eric P. Winer, Elizabeth A. Mittendorf, Eliezer M. Van Allen, Geoffrey I. Shapiro, Sara M. Tolaney

Supplementary Table 3







We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC treated with 0–1 prior lines of chemotherapy received cisplatin 75 mg/m2 i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response. A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had BRCA2 mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13–44], and median progression-free survival was 4.9 months (95% CI, 2.3–5.7). Treatment-related grade 3–5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration. Among patients with mTNBC treated with 0–1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation.

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