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Mini Oral session 2

96MO - A Risk Analysis of Alpelisib (ALP)-Induced Hyperglycemia (HG) Using Baseline Factors in Patients (pts) With Advanced Solid Tumors and Breast Cancer (BC): A Pooled Analysis of X2101 and SOLAR-1


08 May 2021


Mini Oral session 2


Tumour Site

Breast Cancer


Jordi Rodon


Annals of Oncology (2021) 32 (suppl_2): S60-S78. 10.1016/annonc/annonc508


J. Rodon1, D. Demanse2, H.S. Rugo3, F. André4, F. Janku5, I. Mayer6, H. Burris7, R. Simo8, A. Farooki9, H. Hu10, I. Lorenzo11, C. Quadt12, D. Juric13

Author affiliations

  • 1 Houston/US
  • 2 Novartis Pharma AG, Basel/CH
  • 3 UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 4 Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 5 The University of Texas M. D. Anderson Cancer Center, 77030 - Houston/US
  • 6 Vanderbilt-Ingram Cancer Center, Nashville/US
  • 7 Sarah Cannon Research Institute, 37203 - Nashville/US
  • 8 Autonomous University of Barcelona, Barcelona/ES
  • 9 Memorial Sloan Kettering Cancer Center, New York/US
  • 10 Novartis Pharmaceuticals Corporation, East Hanover/US
  • 11 Novartis Farmacéutica SA, Madrid/ES
  • 12 Novartis International AG - Basel, 4056 - Basel/CH
  • 13 Massachusetts General Hospital Cancer Center, 2114 - Boston/US


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Abstract 96MO


ALP + fulvestrant is approved for PIK3CA-mutated, HR+/HER2– advanced BC in the US and EU. HG is an on-target adverse event (AE) of ALP and the most common all grade (G) and G3/4 AE in the phase III SOLAR-1 trial. Antihyperglycemic agents (AHAs) and ALP dose modifications (mods) and discontinuations (discs) were used to manage this AE (Table). We present a pooled risk factor model using safety sets of the phase I X2101 (NCT01219699) and SOLAR-1 (NCT02437318) trials and its application to SOLAR-1 data.


Pts (505) were randomly divided into training (405 pts) and testing sets (100 pts). Baseline factors for HG were identified, multiple models tested, and a random forest model was used to categorize pts as high or low risk for G3/4 HG based on 5 baseline factors (fasting plasma glucose [FPG], BMI, HbA1c, monocyte counts, and age). Performance metrics will be presented.


The training set identified G3/4 HG in 126/131 high (96.2%) vs 3/274 low risk (1.09%) pts, and was validated in the testing set with 20/33 high (60.6%) vs 12/67 low risk (17.9%) pts. A 2-month (mo) analysis of G3/4 HG risk confirmed decreased probability at lower risk scores (area under the curve: training set = 0.991, testing set = 0.767). In all pts in the ALP arm of SOLAR-1, the model found a higher incidence of all-G and G3/4 HG, use of multiple AHAs, and more dose mods and discs in the high vs low risk pts (Table). There was no difference in median PFS in high (11.0 mo) vs low risk (10.9 mo) pts in the ALP arm with PIK3CA mutations. Table: 96MO

HG incidence and management, n (%) All Pts N = 284 High Risk N = 106 Low Risk N = 178
All-G HG 187 (65.8) 101 (95.3) 86 (48.3)
G3/4 HG 108 (38.0) 96 (90.6) 12 (6.7)
Patients who received AHAs 163 (57.4) 94 (88.7) 70 (39.3)
1 AHA 67 (41.1) 24 (25.5) 43 (61.4)
2 AHA 49 (30.1) 31 (33.0) 18 (25.7)
≥3 AHA 47 (28.8) 39 (41.5) 9 (12.9)
Dose mods for any reason (reductions and/or interruption of ALP) 213 (75.0) 92 (86.8) 122 (68.5)
Permanent discs for any reason 244 (85.9) 90 (84.9) 154 (86.5)
Discs due to HG 19 (6.7) 15 (14.2) 4 (2.2)


Risk modeling identified 5 baseline factors (FPG, BMI, HbA1c, monocyte counts, and age) associated with a higher probability of ALP-induced G3/4 HG. High risk pts had higher rates of AHAs and ALP mods. This model could be used clinically to identify pts at high risk for ALP-induced HG. Regardless of risk, pts with PIK3CA mutations derived a similar PFS benefit from ALP.

Clinical trial identification

NCT02437318, NCT01219699.

Editorial acknowledgement

This abstract was developed with editorial assistance provided by Daniele Cary, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.


Novartis Pharmaceuticals Corporation.


J. Rodon: Honoraria (self), Advisory/Consultancy: Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceuticals/Klus Pharma, Spectrum Pharmaceuticals, Inc., Pfizer, Roche Pharmaceuticals, Ellipses Pharma, Certera, Bayer, Molecular Partners, Nov; Research grant/Funding (institution): Bayer, Novartis, Blueprint Pharmaceuticals, Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAlta, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline, Ipsen; Travel/Accommodation/Expenses: ESMO, Department of Defense, Merck Sharp & Dohme, Louisiana State University, Kelun Pharmaceuticals/Klus Pharma, Huntsman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute, King Abdullah International Medical Research Center, Bayer, WIN Co; Non-remunerated activity/ies: European Journal of Cancer, VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline. D. Demanse: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. H.S. Rugo: Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Celsion; Research grant/Funding (institution): Merck; Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: Bayer. F. André: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche. I. Mayer: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Puma; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Macrogenics; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Cylacel. H. Burris: Honoraria (institution), Research grant/Funding (institution): AstraZeneca, Incyte, Novartis, Bayer, Pfizer; Honoraria (institution): FORMA Therapeutics, Celgene, Daiichi Sankyo, HCA Healthcare/Sarah Cannon, GRAIL; Research grant/Funding (institution): Roche/Genentech, Bristol-Myers Squibb, MedImmune, Macrogenics, Boehringer Ingelheim, Lilly, Seattle Genetics, Merck, Agios, Jounce Therapeutics, Moderna, CytomX, GlaxoSmithKline, Verastern, Tesaro, BioMed Valley Discoveries, TG Therapeutics, Vertex, eFFEC. A. Farooki: Leadership role: Novartis. H. Hu, I. Lorenzo, C. Quadt: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. D. Juric: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: EMD Serono. All other authors have declared no conflicts of interest.

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