Abstract 1475
Background
Approximately 40% of patients (pts) with HR+, HER2– BC have mutations (mut) in PIK3CA with hyperactivation of the PI3K pathway and relative endocrine resistance. In the phase 3 SOLAR-1 trial, treatment with the α-selective PI3K inhibitor ALP with FUL significantly prolonged progression-free survival (PFS) vs placebo [PBO] + FUL in the PIK3CA-mut cohort (median PFS [mPFS], 11.0 vs 5.7 mo; HR 0.65; P < 0.001). Here, we report data for pts with and without VM in the PIK3CA-mut cohort of SOLAR-1.
Methods
Pts with HR+, HER2– ABC with progression on/after aromatase inhibitor received ALP 300 mg QD (or PBO) + FUL 500 mg. Efficacy, including PFS and response, and safety were assessed. Pts were stratified according to presence of lung and/or liver metastases and prior CDK4/6 inhibitor treatment.
Results
Of 341 pts with PIK3CA mut, 193 (56.6%) had VM. Tumor responses were improved with ALP vs PBO in pts with or without VM (Table). The majority (n = 170; 88.1%) of pts with VM had lung and/or liver metastases and mPFS was 9.0 vs 3.7 mo in the ALP (n = 84) vs PBO (n = 86) arms (HR 0.62; 95% CI, 0.44-0.89). PFS HRs (95% CI) for ALP vs PBO in pts with presence of liver metastases (ALP, n = 49; PBO, n = 54) or lung involvement (ALP, n = 57; PBO, n = 68) were 0.58 (0.37-0.90) and 0.65 (0.42-1.01), respectively. PFS HRs (95% CI) for ALP vs PBO in pts without lung and/or liver metastases (ALP, n = 85; PBO, n = 86) and in pts with bone-only metastases (ALP, n = 42; PBO, n = 35) were 0.69 (0.47-1.01) and 0.62 (0.33-1.18), respectively. mPFS for pts with bone-only metastases in the ALP vs PBO arms was 19.1 vs 13.0 mo.Table:
342P
Visceral Metastases, includes pts with lung, liver, and other visceral metastases | Nonvisceral Metastases, includes pts with bone-only metastases | |||
---|---|---|---|---|
(n = 193) | (n = 148) | |||
ALP+FUL | PBO+FUL | ALP+FUL | PBO+FUL | |
(n = 93) | (n = 100) | (n = 76) | (n = 72) | |
Best % change from baseline in sum of target lesion diameters | 79% | 43% | 69% | 45% |
Clinical Benefit Rate (CBR), n (%) | 52 (56) | 38 (38) | 52 (68) | 40 (56) |
Conclusions
Treatment benefit from ALP + FUL was maintained across pt subgroups analyzed, including pts with VM and bone-only metastases, and was consistent with the benefit observed in the PIK3CA-mut cohort in SOLAR-1.
Clinical trial identification
NCT02437318.
Editorial acknowledgement
Medical editorial assistance was provided by Joe Hodgson and Amanda Vreeland, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceutical Corporation.
Funding
Novartis Pharmaceutical Corporation.
Disclosure
M. Campone: Research grant / Funding (self), Grant: Novartis; Research grant / Funding (self), Personal fee: Roche; Research grant / Funding (self), Personal fee: AstraZeneca; Research grant / Funding (self), Personal fee: Pfzier; Advisory / Consultancy, Advisory board fees to the institution: Servier; Advisory / Consultancy, NA: Lilly; Advisory / Consultancy, Advisory board fees to the institution: Sanofi; Advisory / Consultancy, Advisory board fees to the institution: Accord; Research grant / Funding (self), Grant: Tessaro. H.S. Rugo: Research grant / Funding (self), Research: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics and Macrogenics; Travel / Accommodation / Expenses, Travel: Lilly, Mylan, Pfizer, Amgen, Merck and Puma. G. Rubovszky: Advisory / Consultancy, Conduct of clinical trials as investigator: Novartis. F. André: Research grant / Funding (institution), Research: Novartis, AstraZeneca, Pfizer, Lilly, Roche. S. Loibl: Honoraria (institution), honorario: Novartis; Honoraria (institution), honorario: Pfzier; Honoraria (institution), honorario: Amgen; Honoraria (institution), honorario: Celgene; Honoraria (institution), honorario: Roche; Honoraria (institution), honorario: AstraZeneca; Honoraria (institution), honorario: Abbvie; Honoraria (institution), honorario: Lilly; Honoraria (institution), honorario: Daichi; Honoraria (institution), honorario: Eirgenix. H. Iwata: Honoraria (institution), Advisory / Consultancy, Support of parent study and funding of editorial support, honoraria and consulting: Novartis; Honoraria (institution), Advisory / Consultancy, Consulting: F. Hoffmann-La Roche via Chugai; Honoraria (institution), Advisory / Consultancy, Consulting: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Consulting: Lilly; Honoraria (institution), Advisory / Consultancy, Consulting: Pfzier; Honoraria (institution), Advisory / Consultancy, Consulting: Daiichi-Sankyo. P.F. Conte: Speaker Bureau / Expert testimony, Speakers Bureau: Roche/Genentech; Novartis; AstraZeneca; Research grant / Funding (institution), Research: Roche Relationship (Institution); Novartis (Institution); Merck Serono (Institution); Travel / Accommodation / Expenses, Travel: Novartis; Celgene;AstraZeneca. I. Mayer: Research grant / Funding (institution), Institutional research funding and Ad board: Novartis; Research grant / Funding (institution), Institutional research funding and Ad board: Genentech; Research grant / Funding (institution), Institutional research funding: Pfzier; Advisory / Consultancy, Ad board: Eli-Lilly; Advisory / Consultancy, Ad board: AstraZeneca; Advisory / Consultancy, Ad board: GSK; Advisory / Consultancy, Ad board: Macrogenics; Advisory / Consultancy, Ad board: Seattle Genetics; Advisory / Consultancy, Ad board: Immunomedic. D. Juric: Advisory / Consultancy, Scientific Advisory Board: Novartis; Speaker Bureau / Expert testimony, Scientific Advisory Board: Genentech; Advisory / Consultancy, Scientific Advisory Board: Eisai; Advisory / Consultancy, Scientific Advisory Board: Ipsen; Advisory / Consultancy, Scientific Advisory Board: EMD Serono. T. Yamashita: Honoraria (self), Research grant / Funding (self): Chugai; Honoraria (self), Research grant / Funding (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (self): Kyowa Kirin; Honoraria (self): Eisai, Novartis, Taiho, AstraZeneca, Pfzier Japan. I. Lorenzo: Full / Part-time employment, Employee: Novartis. A. Ridolfi: Full / Part-time employment, Employee: Novartis. E.M. Ciruelos: Honoraria (self), honorario: Consultancy for Novartis, Lilly, Roche, Pfizer; Advisory / Consultancy, Consulting: Novartis, Pfizer, Lilly, Roche; Speaker Bureau / Expert testimony, Speakers Bureau: Novartis, Pfizer, Lilly, Roche; Travel / Accommodation / Expenses, Travel: Roche, Pfizer.
Resources from the same session
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract