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  • 1From the Royal Marsden Hospital and Institute of Cancer Research (N.C.T.) and the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London (P. Schmid), London, and Roche, Welwyn Garden City (E.T., G.L.) - all in the United Kingdom; Seoul National University Hospital, Seoul National University College of Medicine, Cancer Research Institute, Seoul National University, Seoul, South Korea (S.-A.I.); Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (C. Saura); Mass General Cancer Center, Department of Medicine, Harvard Medical School, Boston (D.J.); Winship Cancer Institute at Emory University, Atlanta (K.K.); Genentech, San Francisco (N.S., T.J.S., K.E.H., J.L.S., C. Song); the Breast and Early Drug Development Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College - both in New York (K.L.J.); the German Breast Group, Neu-Isenburg, and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt - both in Germany (S. Loibl); the Division of Cancer Research and Clinical Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, and the Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, VIC - both in Australia (S. Loi); the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand (P. Sunpaweravong); the Department of Medicine, University of Parma, Parma, and the Medical Oncology and Breast Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori," Meldola - both in Italy (A.M.); the Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing (H.L.), Harbin Medical University, Harbin (Q.Z.), and the University Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (R.L.) - all in China; and Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland (Z.N.).

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Summary
This summary is machine-generated.

Inavolisib combined with palbociclib-fulvestrant significantly improved progression-free survival in patients with PIK3CA-mutated breast cancer. This combination therapy demonstrated enhanced antitumor activity but also an increased incidence of toxic effects.

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Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Inavolisib is a potent inhibitor of PIK3CA-mutated phosphatidylinositol 3-kinase alpha.
  • It promotes degradation of mutated p110α, showing synergistic effects with palbociclib-fulvestrant in preclinical and early-phase studies.

Purpose of the Study:

  • To evaluate the efficacy and safety of first-line inavolisib plus palbociclib-fulvestrant versus placebo plus palbociclib-fulvestrant in PIK3CA-mutated advanced breast cancer.

Main Methods:

  • A phase 3, double-blind, randomized trial compared inavolisib (9 mg daily) plus palbociclib-fulvestrant against placebo plus palbociclib-fulvestrant.
  • The study included patients with PIK3CA-mutated, HR+, HER2- locally advanced or metastatic breast cancer with prior endocrine therapy relapse.

Main Results:

  • Median progression-free survival was 15.0 months with inavolisib vs. 7.3 months with placebo (HR 0.43, P<0.001).
  • Objective response rates were 58.4% (inavolisib) vs. 25.0% (placebo).
  • Higher rates of neutropenia, hyperglycemia, and stomatitis were observed with inavolisib, though discontinuations due to adverse events were low (6.8%).

Conclusions:

  • Inavolisib plus palbociclib-fulvestrant significantly improves progression-free survival in PIK3CA-mutated advanced breast cancer.
  • The combination therapy shows increased toxic effects, but patient discontinuation rates due to adverse events remain low.