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
5629 - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumor infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion
Presenter: Luca Campedel
Session: Poster Display session 2
Resources:
Abstract
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract