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
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract