Abstract | PURPOSE: This phase II study investigated daily or weekly sapanisertib (a selective dual inhibitor of mTOR complexes 1 and 2) in combination with fulvestrant. PATIENTS AND METHODS: RESULTS: Among 141 enrolled patients, baseline characteristics were balanced among treatment arms, including prior cyclin-dependent kinase-4/6 (CDK4/6) inhibitor treatment in 33% to 35% of patients. Median progression-free survival (PFS; primary endpoint) was 3.5 months in the single-agent fulvestrant arm, compared with 7.2 months for fulvestrant plus sapanisertib daily [HR, 0.77; 95% confidence interval (CI), 0.47-1.26] and 5.6 months for fulvestrant plus sapanisertib weekly (HR, 0.88; 95% CI, 0.53-1.45). The greatest PFS benefits were seen in patients who had previously received CDK4/6 inhibitors. The most common adverse events were nausea, vomiting, and hyperglycemia, all occurring more frequently in the combination therapy arms. Treatment discontinuation due to adverse events occurred more frequently in the two combination therapy arms than with single-agent fulvestrant (32% and 36% vs. 4%, respectively). CONCLUSIONS:
Fulvestrant plus sapanisertib daily/weekly resulted in numerically longer PFS in patients with ER+/HER2- advanced or metastatic breast cancer, compared with single-agent fulvestrant. The combination was associated with increased toxicity. Further development of sapanisertib using these dosing schedules in this setting is not supported by these data.
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Authors | José Á García-Sáenz, Noelia Martínez-Jáñez, Ricardo Cubedo, Yolanda Jerez, Ainhara Lahuerta, Santiago González-Santiago, Nieves Ferrer, Manuel Ramos, Jose L Alonso-Romero, Antonio Antón, Eva Carrasco, Jingjing Chen, Rachel Neuwirth, Kevin Galinsky, Sylvie Vincent, E Jane Leonard, Dennis Slamon |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 28
Issue 6
Pg. 1107-1116
(03 15 2022)
ISSN: 1557-3265 [Electronic] United States |
PMID | 34980598
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | ©2022 The Authors; Published by the American Association for Cancer Research. |
Chemical References |
- Aromatase Inhibitors
- Pyrazoles
- Pyrimidines
- Receptors, Estrogen
- Fulvestrant
- Receptor, ErbB-2
- sapanisertib
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects)
- Aromatase Inhibitors
- Breast Neoplasms
(pathology)
- Female
- Fulvestrant
- Humans
- Postmenopause
- Pyrazoles
- Pyrimidines
- Receptor, ErbB-2
(therapeutic use)
- Receptors, Estrogen
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