Senologie - Zeitschrift für Mammadiagnostik und -therapie 2021; 18(02): e36-e37
DOI: 10.1055/s-0041-1730220
Abstracts
Senologie

A phase I/Ib study evaluating GDC-0077 (inavolisib) + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC)

P Schmid
1   Barts Cancer Institute, Queen Mary University of London, London, Vereinigtes Königreich
,
PL Bedard
2   Princess Margaret Cancer Center, University of Toronto, Toronto, Kanada
,
K Jhaveri
3   Memorial Sloan Kettering Cancer Center, New York, Vereinigte Staaten von Amerika
,
A Cervantes
4   University of Valencia, Valencia, Spanien
,
V Gambardella
4   University of Valencia, Valencia, Spanien
,
E Hamilton
5   Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Vereinigte Staaten von Amerika
,
A Italiano
6   Institut Bergonie, Bordeaux, Frankreich
,
K Kalinsky
7   Columbia University Irving Medical Center, New York, Vereinigte Staaten von Amerika
,
IE Krop
8   Dana-Farber Cancer Institute, Boston, Vereinigte Staaten von Amerika
,
M Oliveira
9   Vall d’Hebron University Hospital, Barcelona, Spanien
,
C Saura
9   Vall d’Hebron University Hospital, Barcelona, Spanien
,
N Turner
10   Royal Marsden Hospital and Institute of Cancer Research, London, Vereinigtes Königreich
,
A Varga
11   Gustave Roussy Cancer Campus, Villejuif, Frankreich
,
K Hutchinson
12   Genentech Inc., South San Francisco, Vereinigte Staaten von Amerika
,
G Lei
13   Roche, Welwyn Garden City, Vereinigtes Königreich
,
S Royer-Joo
12   Genentech Inc., South San Francisco, Vereinigte Staaten von Amerika
,
P Thomas
12   Genentech Inc., South San Francisco, Vereinigte Staaten von Amerika
,
Schutzman JL
12   Genentech Inc., South San Francisco, Vereinigte Staaten von Amerika
,
D Juric
14   Massachusetts General Hospital, Boston, Vereinigte Staaten von Amerika
› Author Affiliations
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Background Inavolisib (GDC-0077) is a PI3Kα-selective inhibitor and mutant-PI3Kα-degrader demonstrating antitumor activity in PIK3Camut-BC xenograft-models. Phase-I/Ib-data of inavolisib + palbo + fulvestrant in PIK3CAmut, HR+/HER2-neg-mBC are presented (ongoing study; NCT03006172).

Methods Safety, pharmacokinetics, and preliminary antitumor activity (clinical benefit rate [CBR], partial response [PR]) of 9mg oral daily inavolisib + 125mg palbo 21/28 days + 500mg fulvestrant on day 1 (28-day cycles) were assessed in non-randomized arms E+F. Arm F included obese and/or pre-diabetic pts receiving metformin ≤ 2000 mg daily.

Results 28 pts were enrolled (13/Arm E, 15/Arm F). Median inavolisib treatment-duration was 7.8 months/E and 6.5 months/F. Inavolisib cumulative dose intensity was 98%/88%. Thirteen patients (46%) discontinued treatment: 11, radiographic progression (3/E, 8/F); one, AE/panniculitis; one withdrew. Grade ≥ 3 treatment-related AEs (≥ 2 pts) were neutropenia (62%) and hyperglycemia (23%) (Arm E); hyperglycemia and neutropenia (47% each), and anemia (13%) (Arm F). AEs led to inavolisib dose reduction in 2 (15%/E) and 4 (27%/F) patients. The pharmacokinetics of inavolisib in combination with palbo+fulvestrant were similar to single agent inavolisib. 7/25 pts (28%) with measurable disease had a PR (50%/Arm E; 13%/Arm F). CBR was 62%/E and 60%/F. PIK3CAmut allele frequency by ctDNA analysis decreased during treatment in most patients.

Conclusion This study demonstrated a manageable safety profile when combining 9mg inavolisib with palbo + fulvestrant (standard doses), similar pharmacokinetics to single agent inavolisib, preliminary antitumor activity, and modulation of PIK3CAmut allele frequency in ctDNA. In obese/pre-diabetic patients, hyperglycemia was frequent despite metformin-therapy.



Publication History

Article published online:
01 June 2021

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