American Association for Cancer Research
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Table S6 from A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2–Positive Metastatic Breast Cancer

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posted on 2023-04-03, 21:44 authored by Sheau W. Lok, James R. Whittle, François Vaillant, Charis E. Teh, Louisa L. Lo, Antonia N. Policheni, Alice R.T. Bergin, Jayesh Desai, Sarah Ftouni, Luke C. Gandolfo, Danny Liew, He K. Liu, G. Bruce Mann, Kate Moodie, Anand Murugasu, Bhupinder Pal, Andrew W. Roberts, Mark A. Rosenthal, Kylie Shackleton, Maria João Silva, Zhen R. Siow, Gordon K. Smyth, Leanne Taylor, Avraham Travers, Belinda Yeo, Miriam M. Yeung, Andjelija Zivanovic Bujak, Sarah-Jane Dawson, Daniel H.D. Gray, Jane E. Visvader, Geoffrey J. Lindeman

Supplementary Table S6


National Health and Medical Research Council

Victorian Cancer Agency

National Breast Cancer Foundation




Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0–8) were treated with daily tamoxifen (20 mg) and venetoclax (200–800 mg). Apart from uncomplicated “on-target” lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and the clinical benefit rate was 75%. Treatment responses were preempted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations. In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors.See related commentary by Drago et al., p. 323.This article is highlighted in the In This Issue feature, p. 305