Abstract 5535
Background
PIK3CA mutations occur in ≈ 40% of HR+/HER2− breast cancers. In the phase III SOLAR-1 study (NCT02437318), ALP (PI3Kα inhibitor) + FUL significantly prolonged progression-free survival vs placebo (PBO) + FUL in patients (pts) with HR+/HER2− ABC, prior endocrine therapy, and PIK3CA mutations (HR 0.65; P < 0.001; Andre F, et al. NEJM. 2019). We report pt management details of key AESIs from SOLAR-1.
Methods
Pts received ALP + FUL (n = 284) or PBO + FUL (n = 287). Safety was assessed per CTCAE v4.03 and regardless of PIK3CA mutation status. We evaluated time to onset and management of key AESIs in patients receiving ALP.
Results
The median ALP treatment exposure was 5.5 mo. As previously reported, the most common any-grade AESIs were hyperglycemia, diarrhea, and rash (Table). Rates of ALP discontinuation and median times to onset and improvement are presented in the table. Supportive medication was frequently used to manage hyperglycemia, diarrhea, and rash. In pts with anti-rash medication initiated prior to onset of rash (n = 86), 60 (69.8%) received antihistamines. Use of anti-rash medication prior to onset of rash was associated with decreased frequency of rash (26.7% vs 53.9% in the overall population) and decreased reported grade (grade 3, 11.6% vs 20.1%). During the study, the implementation of more detailed AE management guidelines decreased treatment discontinuation due to any-grade AEs (29.2% vs 20.7%) and grade ≥ 3 events (18.1% vs 7.9%) between the first 50% of pts randomized and the last 50% of patients randomized.Table:
324P
Hyperglycemia | Diarrheaa | Rash | |
---|---|---|---|
n = 284 | |||
Pts with any-grade event, n (%) | 187 (65.8) | 164 (57.7) | 153 (53.9) |
-ALP discontinuation due to event, n (%) | 19 (10.2) | 8 (4.9) | 12 (7.8) |
-Received supportive medication, n (%) | 163 (87.2) | 104 (63.4) | 134 (87.6) |
-Most-common supportive medication for any-grade event, n (%) | Metformin, 142 (87.1) | Antipropulsives, 69 (66.3) | Steroids, 113 (84.3)b,c |
Pts with ≥ grade-3 event, n (%) | 110 (38.7)d | 19 (6.7) | 28 (9.9)e |
-Time to onset, median (range), days | 15 (5-395)d | 139 (10-470) | 13 (9-571)e |
-Time to improvement by ≥ 1 grade, median (95% CI), days | 6 (4-7)d,f | 18 (9-45) | 11 (8-NE)e |
Based on preferred term.
bNote that this is for pts who already had developed rash, which is different from pts who received medication before the onset of rash.
cIncludes both topical and systemic.
dBased on fasting plasma glucose values.
eBased on single preferred term.
fRange.
Conclusions
Adverse events associatated with ALP were manageable, improved with appropriate intervention (medication and/or ALP dose interruptions/modifications), and were generally reversible upon treatment discontinuation. Use of anti-rash medication prior to rash onset reduced the frequency and grade of rash.
Clinical trial identification
NCT02437318.
Editorial acknowledgement
Tara Wabbersen of MediTech Media, LLC funded by Novartis.
Legal entity responsible for the study
Novartis.
Funding
Novartis Pharmaceuticals Corp.
Disclosure
H.S. Rugo: Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer Inc.; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme Corp.; Research grant / Funding (institution): Novartis International AG; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly and Company; Research grant / Funding (institution): Genentech, Inc.; Research grant / Funding (institution): Oklahoma Blood Institute; Research grant / Funding (institution): Odonate Therapeutics, Inc.; Research grant / Funding (institution): Daiichi Sankyo Company, Limited; Travel / Accommodation / Expenses: Mylan N.V.; Travel / Accommodation / Expenses: Amgen Inc.; Travel / Accommodation / Expenses: Puma Biotechnology, Inc. F. André: Research grant / Funding (institution): Novartis International AG; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer Inc.; Research grant / Funding (institution): Eli Lilly and Company; Research grant / Funding (institution): F. Hoffmann-La Roche Ltd. T. Yamashita: Honoraria (self), Research grant / Funding (institution): Chugai Pharma USA, Inc; Honoraria (self): Eisai Inc.; Honoraria (self): Novartis International AG; Honoraria (self): Taiho Oncology, Inc.; Honoraria (self), Research grant / Funding (institution): Nippon Kayaku Co.,Ltd.; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Pfizer Inc. J. Cruz Jurado: Honoraria (self): Novartis International AG; Honoraria (self): Genentech, Inc.; Honoraria (self): Elsai; Honoraria (self): Ipsen; Honoraria (self): EMD Serono. D. Juric: Honoraria (self): Novartis International AG; Honoraria (self): Genentech, Inc.; Honoraria (self): Eisai Inc.; Honoraria (self): Ipsen Pharma; Honoraria (self): EMD Serono, Inc. I. Mayer: Honoraria (self), Research grant / Funding (institution): Novarts International AG; Research grant / Funding (institution): Genentech, Inc.; Research grant / Funding (institution): Pfizer, Inc.; Honoraria (self): Eli Lilly and Company; Honoraria (self): AstraZeneca; Honoraria (self): GlaxoSmithKline plc.; Honoraria (self): MacroGenics, Inc. E.M. Ciruelos: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis International AG; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer Inc. H. Iwata: Honoraria (self), Research grant / Funding (institution): Novartis International AG; Honoraria (self): F. Hoffmann-La Roche via Chugai; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer, Inc.; Honoraria (self): Eli Lilly and Company; Honoraria (self): Daiichi Sankyo Company, Ltd. P.F. Conte: Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis International AG; Speaker Bureau / Expert testimony, Research grant / Funding (institution): F. Hoffmann-La Roche Ltd; Speaker Bureau / Expert testimony: Genentech, Inc.; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): EMD Serono, Inc.; Travel / Accommodation / Expenses: Celgene Corporation. M. Campone: Research grant / Funding (institution): Novartis International AG; Honoraria (self), Research grant / Funding (institution): F. Hoffmann-La Roche Ltd; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer, Inc.; Honoraria (institution): Servier Laboratories; Honoraria (institution): Sanofy; Honoraria (institution): Accord; Research grant / Funding (institution): Tessaro. C. Wilke: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. D. Mills: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis International AG. M. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. S. Loibl: Honoraria (institution): Novartis International AG; Honoraria (institution): Pfizer, Inc.; Honoraria (institution): Celgene Corporation; Honoraria (institution): Amgen; Honoraria (institution): F. Hoffmann-La Roche Ltd; Honoraria (institution): AstraZeneca; Honoraria (institution): Abbvie; Honoraria (institution): Eli Lilly and Company; Honoraria (institution): Daiichi Sankyo Company, Ltd; Honoraria (institution): Eirgenix. All other authors have declared no conflicts of interest.
Resources from the same session
4732 - Progesterone Receptor Isoform Ratio Dictates Antiprogestins/Progestins Effects on Metastatic Breast Cancer Models
Presenter: Maria Abascal
Session: Poster Display session 2
Resources:
Abstract
5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.
Presenter: Carine Ngo
Session: Poster Display session 2
Resources:
Abstract
1096 - OncotypeDX® predictive nomogram for recurrence score output: a machine learning system based on quantitative immunochemistry analysis - ADAPTED01
Presenter: Fabio Marazzi
Session: Poster Display session 2
Resources:
Abstract
5426 - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer
Presenter: Willeke van der Plas-Krijgsman
Session: Poster Display session 2
Resources:
Abstract
5865 - Patients with a 21-gene assay in South East London differ from the TAILORx trial population
Presenter: Charalampos Gousis
Session: Poster Display session 2
Resources:
Abstract
1312 - Predictive tools in adjuvant breast cancer – what is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict
Presenter: Alice Loft
Session: Poster Display session 2
Resources:
Abstract
2445 - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma?
Presenter: Hee Jun Choi
Session: Poster Display session 2
Resources:
Abstract
2476 - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Presenter: SERAFIN MORALES Murillo
Session: Poster Display session 2
Resources:
Abstract
3761 - Chemotherapy-induced amenorrhea: prognostic impact on premenopausal Egyptian patients with breast cancer
Presenter: Khaled Abdel Karim
Session: Poster Display session 2
Resources:
Abstract
4687 - Predicting the presence of breast cancer using circulating small RNA in the serum
Presenter: Yumiko Koi
Session: Poster Display session 2
Resources:
Abstract