TY - JOUR
T1 - A phase II trial of an alternative schedule of palbociclib and embedded serum TK1 analysis
AU - Krishnamurthy, Jairam
AU - Luo, Jingqin
AU - Suresh, Rama
AU - Ademuyiwa, Foluso
AU - Rigden, Caron
AU - Rearden, Timothy
AU - Clifton, Katherine
AU - Weilbaecher, Katherine
AU - Frith, Ashley
AU - Roshal, Anna
AU - Tandra, Pavan K.
AU - Cherian, Mathew
AU - Summa, Tracy
AU - Haas, Brittney
AU - Thomas, Shana
AU - Hernandez-Aya, Leonel
AU - Bergqvist, Mattias
AU - Peterson, Lindsey
AU - Ma, Cynthia X.
N1 - Funding Information:
Pfizer provided palbociclib and research funding for this trial. This study is also funded in part by St. Louis Men’s Group Against Cancer, and the Alvin J. Siteman Cancer Center. We thank the Siteman Cancer Center for the use of the Biostatistics Shared Resource. We thank patients and their families for participating in this trial.
Funding Information:
Pfizer provided palbociclib and research funding for this trial. This study is also funded in part by St. Louis Men’s Group Against Cancer, and the Alvin J. Siteman Cancer Center. We thank the Siteman Cancer Center for the use of the Biostatistics Shared Resource. We thank patients and their families for participating in this trial.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2− MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6–43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2–36.1%) without G4 in C1, and 40.7% (95% CI: 27.9–54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5–89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11–34.89), 33.5 (17.25–not reached [NR]), and 11.96 (10.43–NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10−4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10−7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range: −206.25–0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov#: NCT3007979.
AB - Palbociclib 3-weeks-on/1-week-off, combined with hormonal therapy, is approved for hormone receptor positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer (MBC). Neutropenia is the most frequent adverse event (AE). We aim to determine whether an alternative 5-days-on/2-days-off weekly schedule reduces grade 3 and above neutropenia (G3 + ANC) incidence. In this single-arm phase II trial, patients with HR+/HER2− MBC received palbociclib 125 mg, 5-days-on/2-days-off, plus letrozole or fulvestrant per physician, on a 28-day cycle (C), as their first- or second-line treatment. The primary endpoint was G3 + ANC in the first 29 days (C1). Secondary endpoints included AEs, efficacy, and serum thymidine kinase 1 (sTK1) activity. At data-cutoff, fifty-four patients received a median of 13 cycles (range 2.6–43.5). The rate of G3 + ANC was 21.3% (95% CI: 11.2–36.1%) without G4 in C1, and 40.7% (95% CI: 27.9–54.9%), including 38.9% G3 and 1.8% G4, in all cycles. The clinical benefit rate was 80.4% (95% CI: 66.5–89.7%). The median progression-free survival (mPFS) (95% CI) was 19.75 (12.11–34.89), 33.5 (17.25–not reached [NR]), and 11.96 (10.43–NR) months, in the overall, endocrine sensitive or resistant population, respectively. High sTK1 at baseline, C1 day 15 (C1D15), and C2D1 were independently prognostic for shorter PFS (p = 9.91 × 10−4, 0.001, 0.007, respectively). sTK1 decreased on C1D15 (p = 4.03 × 10−7), indicating target inhibition. Rise in sTK1 predicted progression, with the median lead time of 59.5 (inter-quartile range: −206.25–0) days. Palbociclib, 5-days-on/2-days-off weekly, met its primary endpoint with reduced G3 + ANC, without compromising efficacy. sTK1 is prognostic and shows promise in monitoring the palbociclib response. ClinicalTrials.gov#: NCT3007979.
UR - http://www.scopus.com/inward/record.url?scp=85126843316&partnerID=8YFLogxK
U2 - 10.1038/s41523-022-00399-w
DO - 10.1038/s41523-022-00399-w
M3 - Article
C2 - 35314693
AN - SCOPUS:85126843316
SN - 2374-4677
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 35
ER -