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
4616 - Alpelisib (ALP) + Endocrine Therapy (ET) by Last Prior Therapy in Patients (pts) With PIK3CA-Mutated Hormone-Receptor Positive (HR+) Human Epidermal Growth Factor Receptor-2-Negative (HER2–) Advanced Breast Cancer (ABC): Additional Study Cohort in BYLieve
Presenter: Eva Ciruelos
Session: Poster Display session 2
Resources:
Abstract
3592 - PRECYCLE: Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy.
Presenter: Tom Degenhardt
Session: Poster Display session 2
Resources:
Abstract
4168 - Efficacy and safety of oral poly (ADP-ribose) polymerase inhibitor fluzoparib in patients with BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer
Presenter: Ning Li
Session: Poster Display session 2
Resources:
Abstract
2785 - Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase 3 study ARIEL3 of rucaparib maintenance treatment
Presenter: Jonathan Ledermann
Session: Poster Display session 2
Resources:
Abstract
3496 - Integrated safety analysis of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with ovarian cancer in the treatment and maintenance settings
Presenter: Rebecca Kristeleit
Session: Poster Display session 2
Resources:
Abstract
2844 - Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers
Presenter: S.Intidhar Labidi-Galy
Session: Poster Display session 2
Resources:
Abstract
1955 - A Prospective Evaluation of Tolerability of Niraparib Dosing Based on Baseline Body Weight (BW) and Platelet (plt) Count: Blinded Pooled Interim Safety Data from the NORA Study
Presenter: Xiaohua Wu
Session: Poster Display session 2
Resources:
Abstract
2539 - Evaluation of Niraparib 200 mg/d as Maintenance Therapy in Recurrent Ovarian Cancer and Associated Thrombocytopenia in a Real-World US Setting
Presenter: Premal Thaker
Session: Poster Display session 2
Resources:
Abstract
1290 - Niraparib initial dose and its’ management in patients with recurrent high-grade serous ovarian cancer.
Presenter: Jacek Grabowski
Session: Poster Display session 2
Resources:
Abstract
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract