5535 - Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): management and time course of key adverse events of special interest (AESIs) in SOLAR-1

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

Based on preferred term.

Note that this is for pts who already had developed rash, which is different from pts who received medication before the onset of rash.

Includes both topical and systemic.

Based on fasting plasma glucose values.

Based on single preferred term.

Range.

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.