Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374).
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ICR Authors
Authors
Gambardella, V
Accordino, MK
Bedard, PL
Cervantes, A
Hamilton, E
Italiano, A
Kalinsky, K
Krop, IE
Oliveira, M
Saura, C
Schmid, P
Turner, NC
Varga, A
Fernandez-Saranillo, A
Jin, Y
Royer-Joo, S
Peters, U
Shankar, N
Schutzman, JL
Juric, D
Jhaveri, KL
Accordino, MK
Bedard, PL
Cervantes, A
Hamilton, E
Italiano, A
Kalinsky, K
Krop, IE
Oliveira, M
Saura, C
Schmid, P
Turner, NC
Varga, A
Fernandez-Saranillo, A
Jin, Y
Royer-Joo, S
Peters, U
Shankar, N
Schutzman, JL
Juric, D
Jhaveri, KL
Document Type
Journal Article
Date
2025-07-01
Date Accepted
2025-05-05
Abstract
BACKGROUND: Inavolisib is a potent and selective PI3Kα inhibitor that promotes degradation of mutated p110α. We report safety from a phase I/Ib dose-escalation/-expansion study (GO39374; NCT03006172) of inavolisib alone or in combination therapies in PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative advanced breast cancer. PATIENTS AND METHODS: Patients received inavolisib [oral once daily (od)] alone, with letrozole (2.5 mg od) or fulvestrant (500 mg intramuscularly 4 weekly) ± palbociclib (125 mg od for 21/28 days); metformin was included in one arm. PRIMARY ENDPOINT: safety and tolerability. RESULTS: At data cutoff (1 January 2024), 190 patients had been treated, of which 179 (94.2%) had discontinued study treatment, mainly due to progressive disease [146 (76.8%)]. Treatment-related any-grade and grade 3-5 adverse events (AEs) occurred in 181 (95.3%) and 107 (56.3%) patients, respectively. Inavolisib-related AEs led to inavolisib withdrawal in 5 (2.6%) and dose reductions/interruptions in 103 (54.2%) patients. Hyperglycemia, diarrhea, stomatitis (grouped terms), and rash (grouped terms) occurred in 129 (67.9%), 124 (65.3%), 93 (48.9%), and 47 (24.7%) patients, respectively. Hyperglycemia, diarrhea, and stomatitis mainly occurred early in treatment, and were manageable with supportive measures (including oral antihyperglycemic agents, common antidiarrheal medications, and dexamethasone mouthwash, respectively) and/or inavolisib dose modifications (dose interruptions with or without dose reductions). Hyperglycemia remained frequent in patients with risk factors, despite early metformin treatment. Rash was mostly grade 1 and required no treatment. Patients treated for ≥1 year [n = 65 (34.2%)] demonstrated encouraging long-term tolerability. CONCLUSIONS: Inavolisib alone or in combination with HR-positive breast cancer therapies demonstrated a manageable safety and tolerability profile, which supports its ongoing development.
Citation
ESMO Open, 2025, 10 (7), pp. 105303 -
Source Title
ESMO Open
Publisher
ELSEVIER
ISSN
2059-7029
eISSN
2059-7029
Collections
Research Team
Molecular Oncology