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Expert Point of View: Komal Jhaveri, MD, FACP


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Komal Jhaveri, MD, FACP

Komal Jhaveri, MD, FACP

Komal Jhaveri, MD, FACP, Attending Physician at Memorial Sloan Kettering Cancer Center, Clinical Director of the Early Drug Development Service, and Assistant Professor of Medicine at Weill Cornell Medical College, served as the study’s invited discussant.

Dr. Jhaveri noted that, in SOLAR-1, the treatment benefit with alpelisib was observed regardless of prior CDK4/6 inhibition, although the population of CDK4/6-exposed patients accounted for just 6% of those enrolled. BYLieve showed the efficacy of alpelisib in a larger population and in patients who received a higher relative dose intensity. The higher dose intensity may have been the result of fewer hypoglycemia-related treatment discontinuations, she suggested, “which highlight the importance of incorporating effective management strategies.”

Comparison to Real-World Data

“What was interesting and really relevant was the information from real-world data of 95 patients with PIK3CA mutations previously treated with CDK4/6 inhibitors from the Flatiron database,” said Dr. Jhaveri; standard treatment in this group yielded a progression-free survival of just 3.5 months. The comparison with the BYLieve cohort, whose progression-free survival was more than double that, “further supports the use of alpelisib plus fulvestrant for hormone receptor–positive, HER2-negative, PIK3CA-mutated endocrine-resistant metastatic breast cancer in the post–CDK4/6 inhibitor setting,” Dr. Jhaveri noted.

Remaining Questions

It will be important to implement management strategies to improve the therapeutic efficacy of PIK3CA inhibitors and decrease the need for dose reductions and discontinuations due to toxicity, Dr. Jhaveri continued. It will also be important to answer certain questions, such as the endocrine therapy partner in patients who have already experienced disease progression on fulvestrant. The activity of AKT inhibitors plus endocrine therapy after CDK4/6 inhibition, in all comers, and the activity of oral selective estrogen receptor degraders in this setting are other unanswered questions.

Finally, Dr. Jhaveri added, clinicians must remind themselves “that although life-prolonging treatments are absolutely necessary for breast cancer, living with preserved quality of life remains a very important goal.” 

DISCLOSURE: Dr. Jhaveri has served as a consultant or advisor to AbbVie, ADC Therapeutics, AstraZeneca, Bristol-Myers Squibb, Genentech, Intellisphere, Jounce Therapeutics, Lilly, Novartis, Pfizer, Spectrum, Synthon, and Taiho Pharmaceutical and has received travel funding from AstraZeneca, Intellisphere, Jounce, Pfizer, and Taiho Pharmaceutical.


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The PIK3CA inhibitor alpelisib appears to be effective in patients with PIK3CA-positive, hormone receptor–positive/HER2-negative advanced breast cancer previously treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor plus an aromatase inhibitor, according to the phase II BYLieve trial.1

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